Evidence Report/Technology Assessment 

Number 130 

Management of Adnexal Mass 

Prepared for: 

Agency for Healthcare Research and Quality 

U.S. Department of Health and Human Services 

540 Gaither Road 

Rockville, MD 20850 

www.ahrq.gov 

Contract No. 290-02-0025 

Prepared by:

Duke Evidence-based Practice Center 

Durham, North Carolina 

Investigators 

Evan R. Myers, MD, MPH 

Lori A. Bastian, MD, MPH 

Laura J. Havrilesky, MD 

Shalini L. Kulasingam, PhD 

Mishka S. Terplan, MD 

Kathryn E. Cline, MHS 

Rebecca N. Gray, DPhil 

Douglas C. McCrory, MD, MHS 

AHRQ Publication No. 06-E004 

February 2006
This report is based on research conducted by the Duke Evidence-based Practice Center 

(EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, 

MD (Contract No. 290-02-0025). The findings and conclusions in this document are those of 

the author(s), who are responsible for its content, and do not necessarily represent the views 

of AHRQ. No statement in this report should be construed as an official position of AHRQ or 

of the U.S. Department of Health and Human Services. 

The information in this report is intended to help clinicians, employers, policymakers, and 

others make informed decisions about the provision of health care services. This report is

intended as a reference and not as a substitute for clinical judgment. 

This report may be used, in whole or in part, as the basis for the development of clinical 

practice guidelines and other quality enhancement tools, or as a basis for reimbursement and 

coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of 

such derivative products may not be stated or implied. 
ii

This document is in the public domain and may be used and reprinted without permission except 

those copyrighted materials noted for which further reproduction is prohibited without the 

specific permission of copyright holders. 

Suggested Citation: 

Myers ER, Bastian LA, Havrilesky LJ, Kulasingam SL, Terplan MS, Cline KE, Gray RN, 

McCrory DC. Management of Adnexal Mass. Evidence Report/Technology Assessment No. 

130 (Prepared by the Duke Evidence-based Practice Center under Contract No. 290-02-0025.) 

AHRQ Publication No. 06-E004. Rockville, MD: Agency for Healthcare Research and Quality. 

February 2006. 

None of the investigators has any affiliations or financial 

involvement that conflicts with the material presented in 

this report. 
iii

Preface 

 The Agency for Healthcare Research and Quality (AHRQ), through its Evidence-Based 

Practice Centers (EPCs), sponsors the development of evidence reports and technology 

assessments to assist public- and private-sector organizations in their efforts to improve the 

quality of health care in the United States. This report was requested and funded by the Division 

of Cancer Prevention and Control, National Center for Chronic Disease Prevention and Health 

Promotion at the Centers for Disease Control and Prevention (CDC). The reports and 

assessments provide organizations with comprehensive, science-based information on common, 

costly medical conditions and new health care technologies. The EPCs systematically review the 

relevant scientific literature on topics assigned to them by AHRQ and conduct additional 

analyses when appropriate prior to developing their reports and assessments. 

 To bring the broadest range of experts into the development of evidence reports and health 

technology assessments, AHRQ encourages the EPCs to form partnerships and enter into 

collaborations with other medical and research organizations. The EPCs work with these partner 

organizations to ensure that the evidence reports and technology assessments they produce will 

become building blocks for health care quality improvement projects throughout the Nation. The 

reports undergo peer review prior to their release. 

 AHRQ expects that the EPC evidence reports and technology assessments will inform 

individual health plans, providers, and purchasers as well as the health care system as a whole by 

providing important information to help improve health care quality. 

 We welcome comments on this evidence report. They may be sent by mail to the Task Order 

Officer named below at: Agency for Healthcare Research and Quality, 540 Gaither Road, 

Rockville, MD 20850, or by e-mail to epc@ahrq.gov. 

Carolyn M. Clancy, M.D. 

Director 

Agency for Healthcare Research and Quality 

Eddie Reed, M.D.

Director, Division of Cancer Prevention and 

Control 

National Center for Chronic Disease Prevention 

and Promotion 

Centers for Disease Control and Prevention

Jean Slutsky, P.A., M.S.P.H. 

Director, Center for Outcomes and Evidence 

Agency for Healthcare Research and Quality 

Beth A. Collins Sharp, R.N., Ph.D. 

Acting Director, EPC Program 

Agency for Healthcare Research and Quality 

Susan Meikle, M.D., M.S.P.H. 

EPC Program Task Order Officer 

Agency for Healthcare Research and Quality 
iv

Acknowledgments 

The authors gratefully acknowledge Jane Kolimaga and Alison Lee for assistance in study 

initiation; Margaret Jamison, PhD, for assistance with analysis of the Nationwide Inpatient 

Sample data set; and Karen Hoffman, MD, for initial work on developing the ovarian cancer 

natural history model. They also thank Mona Saraiya, MD, MPH, and Christie Eheman, PhD, 

from the Centers for Disease Control and Prevention for their valuable input. 
v

Structured Abstract 

Objectives: To assess diagnostic strategies for distinguishing benign from malignant adnexal 

masses. 

Data Sources: MEDLINE® and reference lists of recent reviews; discharge data from the 

Nationwide Inpatient Sample. 

Review Methods: The major diagnostic methods evaluated were bimanual pelvic examination, 

ultrasound (morphology and Doppler velocimetry), MRI, CT, FDG-PET, CA-125, and scoring 

systems that incorporated multiple clinical, laboratory, and radiologic findings. Meta-analysis 

using a random-effects model was used to estimate pooled sensitivity and specificity for 

discriminating benign from malignant. We reviewed evidence for followup strategies for masses 

considered benign, and for adverse outcomes of diagnostic surgery. We also reviewed published 

models of the natural history of ovarian cancer and compared the impact of assumptions about 

natural history on outcomes. 

Results: The majority of studies did not describe whether patients presented with asymptomatic 

masses detected through screening or with symptoms. Prevalence of malignant masses in a U.S. 

postmenopausal screening population was approximately 0.1 percent, while benign masses were 

found in 0.8 to 1.8 percent of women. Pooled (a) sensitivity and (b) specificity were: bimanual 

exam (a) 0.45, (b) 0.90; ultrasound morphology scores (a) 0.86 to 0.91, (b) 0.68 to 0.83; Doppler 

resistive index (a) 0.72, (b) 0.90; pulsatility index (a) 0.80, (b) 0.73; maximum systolic velocity 

(a) 0.74, (b) 0.81; presence of vessels (a) 0.88, (b) 0.78; combined morphology and Doppler (a) 

0.86, (b) 0.91; MRI (a) 0.91, (b) 0.88; CT (a) 0.90, (b) 0.75; FDG-PET (a) 0.67, (b) 0.79; and 

CA-125 (a) 0.78, (b) 0.78. Both sensitivity and specificity of CA-125 were better in 

postmenopausal than in premenopausal women. In modeled outcomes, combinations of imaging 

and CA-125 were both more sensitive and more specific than either alone. Performance of 

scoring systems in validation studies was consistently worse than in development studies; the 

highest demonstrated specificity observed was 0.91, with a concurrent sensitivity of 0.74. 

Evidence on followup strategies was sparse, although one large study provided good evidence 

for safely following unilocular cysts less than 10 cm in diameter. Overall complication rates in 

studies of surgically managed adnexal masses were low, but important clinical information was 

not reported. 

Conclusions: All diagnostic modalities showed trade-offs between sensitivity and specificity, 

but the available literature does not provide sufficient detail on relevant characteristics of study 

populations to allow confident estimation of the results of alternative diagnostic strategies. 

Although modeling studies may prove useful in evaluating diagnostic algorithms, further work is 

needed to explore the implications of uncertainty about the natural history of ovarian cancer. 

vii

Contents

Executive Summary.......................................................................................................................1

Evidence Report.............................................................................................................................7

Chapter 1. Introduction .................................................................................................................9

 Ovarian Tumors .......................................................................................................................9 

 Definition of an Adnexal Mass..............................................................................................11 

 Detection of an Adnexal Mass...............................................................................................11 

 Types of Adnexal Mass .........................................................................................................12 

 Management of the Adnexal Mass ........................................................................................12 

 Importance of Discriminating Benign from Malignant Masses ............................................13 

 Significance of Clinical Presentation in Evaluation of Management Strategies ...................13 

 Summary................................................................................................................................15 

Chapter 2. Methods.....................................................................................................................17 

 Topic Assessment and Refinement........................................................................................17 

 Analytic Framework ..............................................................................................................18 

 Literature Search and Review................................................................................................21

 Sources.............................................................................................................................21 

 Search Strategies..............................................................................................................21 

 Abstract and Full-text Screening .....................................................................................21 

 Full-text Screening Criteria..............................................................................................22 

 Data Abstraction and Development of Evidence Tables .......................................................24 

 Quality Assessment Criteria ..................................................................................................24 

 Additional Analyses...............................................................................................................27 

 Test Characteristics and Confidence Intervals.................................................................27 

 Prevalence and Event Rates and Confidence Intervals....................................................27 

 Estimation of Pooled Sensitivity and Specificity ............................................................28 

 Estimates of National Rates of Surgery for Adnexal Mass .............................................28 

 Model of Natural History of Ovarian Cancer ..................................................................29 

 Peer Review Process..............................................................................................................31 

Chapter 3. Results .......................................................................................................................33 

 Question 1: Prevalence of Tumor Types ..............................................................................33 

 Approach..........................................................................................................................33 

 Results..............................................................................................................................33 

 Discussion........................................................................................................................35 

 Summary..........................................................................................................................36 

 Question 2: Bimanual Pelvic Examination...........................................................................36 

 Approach..........................................................................................................................36 

 Results of Literature Search and Screening.....................................................................36 

 Study Characteristics .......................................................................................................37 

 Results..............................................................................................................................37 
viii

 Discussion........................................................................................................................41 

 Question 3: Single Modality Tests........................................................................................42 

 Approach..........................................................................................................................42 

 Results of Literature Search and Screening.....................................................................43 

 Ultrasound Morphology...................................................................................................43 

 Ultrasound Doppler Studies.............................................................................................53 

 Combined Ultrasound Morphology and Doppler ............................................................61 

 3D Versus 2D Ultrasound................................................................................................63 

 Other Imaging Modalities................................................................................................64 

 Serum Markers: CA-125.................................................................................................66 

 Other Serum Markers.......................................................................................................69 

 Population-based Studies.................................................................................................70 

 Methodological Issues .....................................................................................................72 

 Summary..........................................................................................................................74 

 Question 4: Explicit Scoring Systems...................................................................................75 

 Approach..........................................................................................................................75 

 Results of Literature Search and Screening.....................................................................76 

 Study Characteristics .......................................................................................................76 

 Diagnostic Accuracy of Scoring Systems........................................................................77 

 Discussion........................................................................................................................86 

 Question 5: Monitoring Women with Suspected Benign Masses ........................................87 

 Approach..........................................................................................................................87 

 Results..............................................................................................................................88 

 Discussion........................................................................................................................91 

 Question 6: Surgical Morbidity and Mortality......................................................................92 

 Approach..........................................................................................................................92 

 Results of Literature Search and Screening.....................................................................93 

 Methodological Quality of Included Studies ...................................................................93 

 Results..............................................................................................................................93 

 Nationwide Inpatient Sample...........................................................................................95 

 Other Outcomes ...............................................................................................................97 

 Discussion........................................................................................................................98 

 Summary..........................................................................................................................98 

 Question 7: Modeling Diagnostic Strategies ........................................................................99 

 Approach..........................................................................................................................99 

 Predicting Outcomes of Management Strategies.............................................................99 

 Models of Ovarian Cancer: Literature Review..............................................................104 

 Discussion......................................................................................................................107 

 Summary........................................................................................................................111 

Chapter 4. Discussion ...............................................................................................................113 

 Limitations of the Report.....................................................................................................113 

 Methodological Issues in the Literature...............................................................................114 

 Description of the Patient Population ............................................................................114 

 Sample Size....................................................................................................................115 
ix

 Blinding..........................................................................................................................115 

 Observer Variability.......................................................................................................115 

 Natural History of Ovarian Cancer................................................................................115 

 Implications of Findings ......................................................................................................115 

 Question 1 ......................................................................................................................115 

 Question 2 ......................................................................................................................116 

 Question 3 ......................................................................................................................116 

 Question 4 ......................................................................................................................116 

 Question 5 ......................................................................................................................116 

 Question 6 ......................................................................................................................116 

 Question 7 ......................................................................................................................117 

Chapter 5. Future Research.......................................................................................................119 

 Minimal Data Reporting ......................................................................................................119 

 Prevalence of Different Types of Adnexal Masses..............................................................119 

 Diagnostic Testing ...............................................................................................................119 

 Scoring Systems...................................................................................................................120 

 Followup Studies .................................................................................................................120 

 Adverse Outcomes of Surgery.............................................................................................120 

 Sensitivity and Specificity of the Pelvic Examination.........................................................121 

 Modeling the Outcomes of Different Screening Strategies .................................................122 

 Modeling the Natural History of Ovarian Cancer................................................................122 

 

Chapter 6. Conclusions .............................................................................................................123 

References and Included Studies ...............................................................................................125 

List of Acronyms/Abbreviations................................................................................................145

Figures 

Figure 1. U.S. ovarian cancer incidence by age and race, 1992-2002..........................................9 

Figure 2. Analytic framework for evidence report .....................................................................19 

Figure 3. Schematic of natural history model.............................................................................30 

Figure 4. Performance of bimanual pelvic examination for detecting the presence of 

 an adnexal mass .....................................................................................................................39 

Figure 5. Performance of bimanual pelvic exam for distinguishing benign from malignant 

adnexal masses.......................................................................................................................41 

Figure 6. Performance of ultrasound scoring according to Sassone’s criteria (1991)................47 

Figure 7. Performance of ultrasound scoring according to DePriest’s criteria (1993) ...............48 

Figure 8. Performance of ultrasound scoring according to Ferrazzi’s criteria (1997)................49 

Figure 9. Performance of ultrasound scoring according to Finkler’s criteria (1988) .................50 

Figure 10. Performance of ultrasound scoring according to various other unvalidated 

criteria.......... .......................................................................................................................51 

Figure 11. Performance of Doppler ultrasound resistance index................................................56 
x

Figure 12. Performance of Doppler ultrasound pulsatility index ...............................................57 

Figure 13. Performance of Doppler ultrasound velocity indices ................................................58 

Figure 14. Performance of Doppler ultrasound for intratumoral blood flow .............................60 

Figure 15. Performance of combined ultrasound morphology and color Doppler.....................62 

Figure 16. Performance of CA-125 ............................................................................................68

Figure 17. Performance of RMI model of Jacobs et al. (1990) in development set and 

 subsequent validation studies using cutoff score of 200........................................................79 

Figure 18. Performance of RMI2 model of Tingulstad et al. (1996) in development 

 set and subsequent validation studies using cutoff score of 200 ...........................................80 

Figure 19. Performance of model of Tailor et al. (1999) in development set and 

 subsequent validation studies.................................................................................................81 

Figure 20. Performance of various other scoring systems in development and validation 

 studies in separate populations...............................................................................................83 

Figure 21. Performance of various other unvalidated models ....................................................84 

Figure 22. Performance of unvalidated simple combination rules in postmenopausal 

 women only...........................................................................................................................85 

Figure 23. Performance of unvalidated simple combination rules in mixed pre- and 

postmenopausal populations ..................................................................................................86 

Figure 24. Schematic of Markov or stochastic model of ovarian cancer natural history .........119 

Figure 25. Alternative model of ovarian cancer history ...........................................................119 

Figure 26. Model predictions of ovarian cancer incidence (black triangles) compared 

 to SEER incidence rates.......................................................................................................119 

Tables 

Table 1. Age-adjusted annual U.S. incidence and mortality per 100,000 women 

 by race and ethnicity, 1992-2002...........................................................................................10 

Table 2. Results of abstract screening and full-text review........................................................23 

Table 3. Included full-text articles by research question ............................................................24 

Table 4. Model variables.............................................................................................................31 

Table 5. Prevalence of tumor types in screening studies............................................................34 

Table 6. Case series and retrospective medical record reviews..................................................34 

Table 7. Sensitivity and specificity of pelvic examination in detecting the presence 

 of an adnexal mass.................................................................................................................38 

Table 8. Sensitivity and specificity of pelvic examination in discriminating benign from 

malignant adnexal masses......................................................................................................40 

Table 9. Detailed description of ultrasound scoring systems .....................................................44 

Table 10. Sensitivity and specificity of ultrasound morphology ................................................46 

Table 11. Ultrasound morphology assessment comparing pre- and postmenopausal 

 status............ .......................................................................................................................52 

Table 12. Sensitivity and specificity of Doppler studies ............................................................55 

Table 13. Study characteristics of simple Doppler visualization................................................59 

Table 14. Doppler studies stratified by menopausal status.........................................................61 

Table 15. 3D versus 2D ultrasound.............................................................................................63 

Table 16. Sensitivity and specificity of other imaging modalities..............................................65 
xi

Table 17. Comparison of MRI, CT, FDG-PET, and ultrasound........................................... 65 

Table 18. CA-125 results stratified by menopausal status.................................................... 69 

Table 19. Population-based screening studies ...................................................................... 71 

Table 20. Effect of classification of LMP tumors as malignant or benign on diagnostic 

 test characteristics ............................................................................................................ 73 

Table 21. Pooled sensitivity and specificity estimates ......................................................... 74 

Table 22. Performance of other scoring systems at initial derivation and subsequent 

 replication in another population ..................................................................................... 82 

Table 23. Studies of followup regimens for benign-appearing lesions ................................ 88 

Table 24. Morbidity in series of patients undergoing surgical management of adnexal 

masses.......... ................................................................................................................. 94

Table 25. Estimated U.S. discharges for exploratory laparotomy and diagnostic 

laparoscopy with discharge diagnoses consistent with adnexal mass, with mortality 

and complication rates ..................................................................................................... 96

Table 26. Estimates for key model parameters.....................................................................100 

Table 27. Predicted outcomes of ultrasound plus Doppler or CA-125 testing to determine 

surgical management in a hypothetical cohort of 100,000 postmenopausal women.......101 

Table 28. Predicted outcomes of serial testing or parallel testing with ultrasound plus 

Doppler or CA-125 testing to determine surgical management in a hypothetical 

cohort of 100,000 postmenopausal women .....................................................................102 

Table 29. Estimated numbers of tests, missed cancers, and surgeries for each strategy ......103 

Table 30. Estimated numbers of tests, missed cancers, and surgeries for each strategy 

 in 1,100 women with known adnexal mass and underlying prevalence of ovarian 

 cancer 10%.......................................................................................................................103 

Table 31. Key input parameters and ranges for the Schapira model ....................................105 

Table 32. Key assumptions and data sources used to derive values for parameters in 

 the Urban model...............................................................................................................106 

Table 33. Inputs and outputs of ovarian cancer models........................................................111 

Appendixes

Appendix A: Exact Search Strings 

Appendix B: List of Excluded Studies 

Appendix C: Sample Data Abstraction Forms 

Appendix D: Evidence Tables 

Appendix E: Peer Reviewers 

The Appendixes and Evidence Tables cited in this report are provided electronically at 

http://www.ahrq.gov/downloads/pub/evidence/pdf/adnexal/adnexal.pdf

1

Executive Summary 

Introduction 

Ovarian cancer is the leading cause of cancer death from gynecologic malignancies in the 

United States, with an annual incidence of over 25,000 and an annual mortality of approximately 

14,000. Cancer incidence increases dramatically with age. 

 The high case-fatality rate has largely been attributed to the fact that most ovarian cancers 

are diagnosed in advanced stages (Stage III, where the cancer has spread beyond the pelvis to 

organs of the upper abdominal cavity, and Stage IV, where the cancer has spread outside of the 

peritoneal cavity), when survival is poor. Stage I cancer (limited to the ovaries) has a survival 

rate of over 90 percent. Thus, there has long been an emphasis on early detection of ovarian 

cancer in the belief that detection in early stages will lead to decreases in morbidity and 

mortality. The detection of a mass in the area of the ovaries and fallopian tubes (the uterine 

adnexae) raises the possibility of ovarian cancer, which necessitates further study to rule out 

malignancy. 

There are two main clinical routes by which an adnexal mass may be detected: (1) women 

with symptoms may have an adnexal mass detected as part of their evaluation for those 

symptoms, either by physical exam or radiographic imaging; (2) the mass may be detected 

during bimanual pelvic examination or radiologic imaging as part of a routine health 

maintenance examination. 

For the purposes of this evidence report, we define an adnexal mass as an enlarged structure 

in the uterine adnexa that can either be palpated on a bimanual pelvic examination or visualized 

using radiographic imaging. 

There are a number of conditions that can be associated with an adnexal mass. These include 

malignancies arising from the ovary and fallopian tube, or metastatic disease from another site 

(such as the breast or gastrointestinal tract), as well as a wide range of benign conditions. For the 

purposes of this evidence report, “management” of the adnexal mass refers to the process by 

which a mass is ultimately classified as benign or malignant. 

The clinical significance of discriminating benign from malignant masses differs depending 

on the clinical setting in which the mass is initially detected. For women with symptoms, in 

whom surgical management may be appropriate whether or not the mass is malignant, the main 

reason to discriminate between benign and malignant lesions is to facilitate referral and 

management by clinicians who have specialized training and experience in managing ovarian 

malignancy, with improved outcomes. For asymptomatic women, discriminating benign from 

malignant disease is important both to ensure appropriate management in the setting of 

malignancy, but also to avoid unnecessary diagnostic procedures, including surgery, in women 

with asymptomatic, nonmalignant conditions. 

The prevalence of malignancy may differ between women with symptomatic and 

asymptomatic masses, which may in turn affect the positive and negative predictive value of a 

test, and, potentially, sensitivity and specificity as well. Prevalence also varies with age and with 

family history. 

This report focuses on the evidence relevant to establishing the most appropriate way to 

distinguish benign from malignant adnexal masses in both symptomatic and asymptomatic 

women. A key consideration throughout the report will be the underlying likelihood of 
2

malignancy in the populations studied, and the impact of this prevalence on the interpretation of 

the results of the reviewed studies. The results of this report are intended primarily to (a) provide 

a resource for clinicians and policymakers developing guidelines on management of adnexal 

masses, and (b) provide a resource for researchers and funding agencies in identifying gaps in 

our knowledge and research priorities. 

Methods 

Working with the Agency for Healthcare Research and Quality (AHRQ), the Centers for 

Disease Control and Prevention (CDC), and members of the technical expert panel, we 

developed seven questions to be addressed, using an analytic framework which incorporated 

prior probability of disease, test results, and outcomes of diagnostic surgery. 

We searched MEDLINE® (1966-September 2004) and the Cochrane Database of Systematic 

Reviews. Searches of these databases were supplemented by reviews of reference lists contained 

in all included articles and in relevant review articles and meta-analyses. The searches yielded a 

total of 1,023 citations. Pairs of readers reviewed each abstract and selected 445 articles for full 

text review. Specific inclusion criteria were developed for each question, and both readers were 

required to agree on inclusion. 

We developed tables to abstract each article, and quality criteria for each question. For 

studies of diagnostic tests, 2-by-2 tables were constructed for each included article, and 

sensitivity, specificity, and positive and negative predictive values, with 95 percent confidence 

intervals (CIs) for each, were calculated. If not provided, we also calculated 95% CIs for articles 

about prevalence and adverse event rates during diagnostic surgery. For diagnostic tests, pooled 

estimates of sensitivity and specificity were calculated using a random-effects model. 

We performed three supplemental analyses. First, we used the Nationwide Inpatient Sample 

(NIS), a nationally representative database containing discharge data from approximately 20 

percent of U.S. hospitals. Using International Classification of Diseases, Ninth Revision (ICD9) codes and the provided corrections for sample weighting, we estimated the number of cases of 

women 15 and older undergoing diagnostic laparoscopy and exploratory laparotomy in 2000 and 

2001 for diagnoses consistent with an adnexal mass. Mortality and morbidity rates for each type 

of procedure within each diagnosis were also estimated. 

Second, we performed a simple decision model based on serial or parallel testing using the 

pooled sensitivity and specificity of various tests to predict outcomes. 

Finally, we used a previously developed Markov model of the natural history of ovarian 

cancer to explore the implications of alternative possible pathways in the development of 

advanced disease – specifically, that some cancers limited to the ovaries (Stage I) may spread to 

the upper abdomen (Stage III) without first spreading to other pelvic organs (Stage II). 

Results 

Question 1: What is the prevalence of various tumor types among women with an adnexal 

mass, stratified by cancer status (malignant vs. benign), age, menopausal status, and size of 

tumor?

In a large screening study in Kentucky the prevalence of malignant masses was 0.09 to 0.18 

percent, and of benign masses 0.8 to 1.8 percent. In 16 case series, the prevalence of malignancy 
3

ranged from 0 to 57 percent, reflecting differences in the referral patterns of the centers where 

the surgery was performed. The prevalences of specific types of masses also varied widely 

within studies. Six studies did not report the proportion of women who were postmenopausal, 

and none of them described whether patients were symptomatic or asymptomatic, or the type of 

evaluation they had undergone prior to surgery. 

Question 2: What are the sensitivity, specificity, and reliability of the bimanual pelvic 

examination?

Pooled sensitivity in five studies for detection of an adnexal mass was 0.45, and pooled 

specificity 0.90. For distinguishing a benign from a malignant mass, pooled sensitivity in 10 

studies was 0.72, specificity 0.92. When only screening studies were included, pooled sensitivity 

was 0.58, specificity 0.98. 

Question 3: Among women with a palpable adnexal mass on exam or a mass identified by 

ultrasound/imaging, what is the sensitivity/specificity of various evaluation modalities including 

ultrasound (transvaginal ultrasound, transabdominal ultrasound, color Doppler, twodimensional [2D] vs. three-dimensional [3D] ultrasound), computer tomography (CT) scan, 

magnetic resonance imaging (MRI) scan, and CA-125 levels for distinguishing benign from 

malignant masses? 

A total of 153 articles were included. For morphologic appearance on ultrasound, pooled 

sensitivities for specific scoring systems ranged from 0.82 to 0.91, and specificities from 0.68 to 

0.81. For Doppler ovarian blood flow studies, pooled (a) sensitivity and (b) specificity were: 

resistive index (a) 0.72 , (b) 0.90; pulsatility index (a) 0.80, (b) 0.73; maximum systolic velocity 

(a) 0.74, (b) 0.81; presence of vessels (a) 0.88, (b) 0.78. The combination of morphology and 

Doppler had pooled sensitivity of 0.86 and specificity of 0.91. 

Pooled (a) sensitivities and (b) specificities of other imaging modalities were: MRI (a) 0.91, 

(b) 0.88; CT (a) 0.90, (b) 0.75; and positron emission tomography using an 18-

Fluorodeoxyglucose tracer (FDG-PET) (a) 0.67, (b) 0.79. 

Pooled sensitivity and specificity for CA-125 at a threshold of 35 U/mL were 0.78 and 0.78, 

respectively. In studies that compared performance by menopausal status, both sensitivity and 

specificity were substantially better in postmenopausal women. 

Characterization of the patient population with respect to presence or absence of symptoms, 

or previously performed tests, was uniformly poor among studies. 

Question 4: What is the accuracy of explicit scoring systems which incorporate various 

combinations of imaging findings, patient risk factors, and/or CA-125 levels for detecting 

malignancy? Have these scoring systems been applied to a population of women before 

laparoscopy or laparotomy? 

We identified 36 studies. Existing validated scoring systems were all developed in mixed 

pre- and postmenopausal populations. The highest demonstrated specificity obtained with these 

scoring systems appears to be in the range of 90 to 95 percent, and, at this range of specificity, 

the sensitivity appears to be in the range of 65 to 80 percent. Performance was consistently 

worse in validation studies (done to confirm the performance of the scoring system) than in 

development studies. Many of the studies were applied to patients immediately prior to surgery, 

but the clinical presentation and prior testing were not described. 

Question 5: Among women with suspected benign masses on initial investigation, what are 

the sensitivity and specificity of monitoring with periodic CA-125 and/or interval ultrasound 

examinations for detecting malignant masses? How does the interval of testing/definition of 

change affect sensitivity and predictive value? 
4

Nine studies were identified, and, because of variable definitions and methods, no definitive 

conclusions could be drawn. In one large study of over 15,000 postmenopausal women, no 

cancers were ultimately diagnosed in a unilocular cyst less than 10 cm (2,763 women) over a 

mean followup of 6.3 years, although three cancers developed after resolution of the cyst or in 

the contralateral ovary. 

Question 6: Among women with adnexal masses, what are the morbidity and mortality from 

diagnostic surgery (laparoscopy or laparotomy)? At what point does the risk of surgery 

outweigh the risk of detecting malignancy? 

In 15 series totaling 4,915 patients, there were three deaths. Morbidity rates were also low. 

Comparative studies suggest lower morbidity with laparoscopy, but there is potential 

confounding, even in randomized studies. None of the included studies provided sufficient 

clinical detail to determine whether risks differed based on ultimate diagnosis. 

In the NIS, both morbidity and mortality were highest in cases with a cancer diagnosis, but 

available codes prevented direct comparisons. In addition, because outpatient laparoscopic 

procedures were not included, both numerators and denominators are likely to be 

underestimated. 

Question 7: What are the estimated trade-offs resulting from various strategies for 

evaluation of the adnexal mass?

Given the summary findings, we were unable to construct comprehensive models to estimate 

the likely outcomes of different strategies. In a preliminary model, serial testing with the best 

imaging study (morphology plus Doppler), followed by CA-125, resulted in fewer missed 

cancers and fewer surgeries than either test alone in postmenopausal women. Parallel testing 

incorporated into a scoring system resulted in slightly fewer missed cancers, but more surgeries 

and twice as many tests. 

Because comprehensive models should ultimately include the natural history of ovarian 

cancer and the possible effects of screening, we identified three articles that simulated this 

natural history. All three assumed that ovarian cancer necessarily progresses through all four 

stages. Using a similarly structured model, we were able to generate estimated incidence and 

stage distribution similar to reported data by allowing some Stage I cancers to progress directly 

to Stage III. By reducing the available detection time for Stage I cancers, this would adversely 

affect the potential effectiveness of screening. 

Discussion 

Limitations of the Literature 

The main limitation in the literature was the failure to adequately describe relevant patient 

characteristics, including the presence or absence of symptoms, and variable reporting of 

menopausal status. Inadequate sample size, lack of blinding, and failure to account for observer 

variability were also common limitations. 

Limitations of the Report 

The report did not include non-English publications. We did not include non-U.S. studies in 

our review of the prevalence of different types of adnexal mass. Given the heterogeneity of 
5

studies, pooled estimation of sensitivity and specificity may not be appropriate. The NIS does 

not include outpatient procedures, and our coding algorithm may have missed some 

complications. 

Future Research 

Research priorities include: a minimal consensus data set on key patient characteristics (with 

results presented stratified by those characteristics); better estimates of prevalence and surgical 

outcomes using data sources that capture inpatient and outpatient encounters, such as Medicare 

or health maintenance organizations; better characterization of patient characteristics in all 

studies; better evidence on the value of the pelvic exam as part of routine health maintenance; 

and development of additional models for simulating the natural history of ovarian cancer and 

evaluating screening, diagnosis, and treatment strategies. 

Conclusions 

Developing an effective and efficient algorithm for the evaluation of any condition requires 

good evidence on the prevalence of the condition at the first diagnostic encounter, and the 

sensitivity and specificity of the potential diagnostic tests to be used. Unfortunately, the 

overwhelming majority of the literature we reviewed did not provide sufficient detail on 

important patient characteristics to allow estimation of the outcomes of different diagnostic 

strategies, either in the context of detecting adnexal masses or distinguishing benign from 

malignant masses. 

All of the diagnostic tests and scoring systems we evaluated exhibited a trade-off between 

sensitivity and specificity – studies of a given test that reported higher sensitivity had lower 

specificity, and vice versa. The bimanual pelvic examination has low sensitivity for both 

detection of adnexal masses and discriminating benign from malignant masses, raising doubts 

about its utility as a screening test in asymptomatic women. In pooled analysis, the combination 

of ultrasound morphology and Doppler blood flow had the best combination of sensitivity and 

specificity, with MRI comparable. In a preliminary model, serial testing with imaging followed 

by CA-125 was both more sensitive and more specific than either test alone; parallel testing 

using both tests incorporated into the Risk of Malignancy Index resulted in fewer missed cancers 

(greater sensitivity) but more surgeries (lower specificity), with twice as many tests. 

Studies of surgical management suffered from the same limitations in terms of description of 

patient characteristics, making estimation of the risks of false positive diagnostic testing 

impossible. 

Ultimately, evaluation of potential strategies for reducing morbidity and mortality from 

ovarian cancer may require use of simulation models, a technique that has proven helpful in 

evaluating prevention strategies for other cancers. Because the natural history of ovarian cancer 

is relatively unknown, testing of alternative models is critical. Although a few sophisticated 

models exist, development of additional models would be helpful, especially in the context of 

evaluating results from ongoing trials of screening. If any of these trials show a benefit from 

screening, then the need for better evidence on the diagnostic evaluation of adnexal masses will 

become even more critical. 

EVIDENCE REPORT 

9 

Chapter 1. Introduction 

Ovarian Tumors 

Cancer of the ovaries is the leading cause of cancer death from gynecologic malignancies in 

the United States, with an annual incidence of over 25,000 and an annual mortality of 

approximately 14,000.1 Cancer incidence increases dramatically with age, being relatively rare 

prior to age 50 (Figure 1). 

Figure 1. U.S. ovarian cancer incidence by age and race, 1992-2002 

Source: Surveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov).2
10 

Ovarian cancer incidence varies by race and ethnicity. Both incidence and mortality are 

highest for white women (Table 1). 

Table 1. Age-adjusted annual U.S. incidence and mortality per 100,000 women by race and ethnicity, 1992-

2002†

White AfricanAmerican Asian/Pacific 

Islander 

Native 

American 

Hispanic 

Incidence 15.1 10.3 10.4 8.9 11.9 

Mortality 9.3 7.6 4.8 5.1 6.2 

† Source: Surveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov).2

 

Malignant tumors of the ovary can either arise in the ovary (primary ovarian cancer) or be the 

result of metastasis from another site, such as the breast or colon. Primary ovarian tumors, 

whether benign or malignant, can arise from three broad types of cells: the cells on the surface 

(epithelial cells); the cells that form eggs (germ cells); and the cells surrounding the eggs, 

including the cells that produce ovarian hormones (sex cord-stromal cells). Epithelial tumors are 

the most common type, accounting for 60 percent of all ovarian tumors and up to 90 percent of 

primary cancers. Sex-cord-stromal tumors account for 10 to 15 percent of all tumors, while 

germ cell tumors account for 25 percent of tumors. In general, sex cord-stromal tumors and 

germ cell tumors are relatively more common in younger premenopausal women. Thus, 

although ovarian cancer is relatively rare in younger women, when it does occur it is more likely 

to be a non-epithelial cancer than cancers in postmenopausal women.3

Within the broad classification of epithelial, sex cord-stromal, and germ cell tumors, tumors 

are further classified by the individual cell types from which they are derived. For example, the 

most common epithelial tumors are serous and mucinous tumors, the most common sex-cord 

stromal tumors are fibromas (arising from the connective tissue surrounding eggs), and the most 

common germ cell tumors are teratomas. Within each histological class, tumors can be benign 

or malignant, based on their ability to metastasize.3

Some epithelial tumors are classified as “borderline” or “low malignant potential” (LMP) 

tumors. These are tumors in which there is no invasion into the ovarian stroma, but for which 

histologic evidence of proliferation exists (increased cell division, changes in the appearance of 

the cell nucleus). There is controversy over whether these tumors represent pre-invasive cancer, 

and, if untreated, would go on to become a cancer, or whether they represent a subtype of tumor 

that has a relatively small chance of becoming a cancer.3

 In estimating the diagnostic accuracy 

of tests for determining whether a mass is benign or malignant, whether LMP tumors are 

classified as benign or malignant can have an effect on the estimates of test performance, as we 

will discuss later in the report. 

Ovarian cancer spreads primarily by dissemination throughout the peritoneal cavity; common 

sites of metastasis are the small and large bowel, the omentum, the liver, and the diaphragm. 

Spread to retroperitoneal lymph nodes is also common. 

Treatment for ovarian cancer consists of surgical removal of the ovaries, fallopian tubes, and 

uterus (if present), along with as much metastatic disease as possible; if there is no obvious 

spread beyond the ovaries, the lymph nodes are sampled to determine if there has been lymphatic 

metastasis. Surgery is followed by chemotherapy, with responsiveness to chemotherapy 

depending on the amount of tumor left after surgical removal and the cell type of tumor, among 

other factors.3
11 

The high case-fatality rate observed in ovarian cancer has largely been attributed to the fact 

that most ovarian cancers are diagnosed in advanced stages (Stage III, where the cancer has 

spread beyond the pelvis to organs of the upper abdominal cavity, and Stage IV, where the 

cancer has spread outside of the peritoneal cavity), when survival is poor. Stage I cancer (limited 

to the ovaries) has a survival rate of over 90 percent. Thus, there has long been an emphasis on 

early detection of ovarian cancer, in the belief that detection in early stages will lead to decreases 

in morbidity and mortality, just as cervical cancer screening has resulted in substantial reductions 

in morbidity and mortality from cervical cancer. The detection of a mass in the area of the 

ovaries and fallopian tubes (the uterine adnexae) raises the possibility of ovarian cancer, which 

necessitates further study to rule out malignancy. 

This evidence report was prepared by the Duke Evidence-based Practice Center, in 

partnership with the Centers for Disease Control and Prevention (CDC) and the Agency for 

Healthcare Research and Quality (AHRQ). The purpose of the report is to provide followup data 

regarding key issues identified at two conferences sponsored by CDC, one in November 2000 on 

broad issues in preventing morbidity and mortality from ovarian cancer,4

 and one in May 2002 

on the use of ultrasound in the diagnosis of ovarian cancer.5

 

Definition of an Adnexal Mass 

For the purposes of this report, we define an adnexal mass as an enlarged structure in the 

uterine adnexa which can either be palpated on a bimanual pelvic examination or visualized 

using radiographic imaging. The normal ovary is approximately 3 cm in length, decreasing in 

size after menopause.6 In terms of physical examination, the precise size definition used in the 

literature is quite variable and, in practice, may also vary depending on the ease with which the 

examination is performed, the patient’s body habitus, the examiner’s experience, the time taken 

during the exam, and the presence of other abnormalities such as uterine fibroids. Historically, 

because of the decrease in size after menopause, any palpable mass in a postmenopausal woman 

has been considered abnormal (the “palpable postmenopausal ovary syndrome”).7 As discussed 

below, some masses may ultimately prove to not be ovarian in origin. 

The definition of an abnormal structure on radiologic imaging is also quite variable. Small 

fluid-filled cysts are quite common in both pre- and postmenopausal women. For the purposes 

of this report, we consider any structure observed during radiologic imaging that prompts 

additional evaluation (such as measurement of serologic markers or further imaging) as a mass. 

 

Detection of an Adnexal Mass 

There are three main clinical routes by which an adnexal mass may be detected. First, 

women with symptoms may have an adnexal mass detected as part of their evaluation for those 

symptoms, either by physical exam or radiographic imaging. Because ovarian cancer often 

presents with vague abdominal symptoms, we would consider any evaluation for symptoms to be 

in symptomatic women. Second, the mass may be detected as part of a routine health 

maintenance examination. Finally, it is possible that an asymptomatic mass could be detected 

during imaging done for another indication. In premenopausal women, the most likely scenario 

where this would occur would be during ultrasound evaluation during pregnancy. Another 

common scenario in peri- or postmenopausal women would be evaluation for uterine bleeding; 
12 

because uterine bleeding is not a common symptom of ovarian cancer, a finding of an adnexal 

mass during evaluation for bleeding could be considered as an incidental finding. Because 

malignancy is rare during pregnancy, and because the technical considerations for both diagnosis 

and management are different, the most appropriate management of masses detected during 

pregnancy, especially if detected serendipitously by ultrasound, is outside of the scope of this 

report. 

We did not identify any literature that would allow an estimate of the proportions of women 

with adnexal masses presenting by each route; as we will discuss, this is a major deficiency of 

the literature. The proportions are likely to vary by setting, referral patterns, patient thresholds 

for seeking care, physician thresholds for diagnostic tests, and other factors. For example, one 

gynecologic oncologist estimated that well over half of the referrals for evaluation in a large 

health maintenance organization were for incidentally detected masses (W. Kinney, personal 

communication). 

Types of Adnexal Mass 

Conditions that can present as an adnexal mass include: 

• Benign primary ovarian tumors – epithelial, sex cord-stromal, and germ cell; 

• Borderline and malignant ovarian tumors – epithelial, sex cord-stromal, and germ cell; 

• Metastatic malignant tumors – most commonly breast and gastrointestinal tract; 

• Masses arising from the fallopian tube – most commonly benign, including hydrosalpinx 

(a large, fluid-filled fallopian tube) and pyosalpinx (an infected, pus-filled fallopian 

tube); primary fallopian tube malignancies can occur, but are relatively rare. 

• Masses arising from the uterus – most commonly benign leiomyomas (fibroids); 

• Masses arising from the gastrointestinal tract – diverticula of the colon, large colonic 

tumors, tumors of the appendix; 

• Masses arising from the urinary tract – pelvic kidneys, diverticula of the ureter; 

• Masses arising from remnants of embryological development; 

• Endometriosis; 

• Pelvic inflammatory disease; 

• Cysts arising from normal ovarian functions, such as development of eggs (follicular 

cysts) and ovulation (corpus luteum cysts). 

Management of the Adnexal Mass 

With such a wide range of potential causes, and with a wide range of appropriate therapeutic 

options, precise diagnosis of a mass, especially in symptomatic women, is important. Once 

diagnosed, a mass may be managed in a variety of ways, ranging from observation to surgical 

removal and chemotherapy. However, a review of the test characteristics of various methods for 

obtaining precise diagnoses of specific conditions, and of the range of medical and surgical 

treatment options for each condition, is beyond the scope of this report. For our purposes, 

“management” of the adnexal mass refers to the process by which a mass is ultimately classified 

as benign or malignant. 
13 

Importance of Discriminating Benign 

from Malignant Masses 

The clinical significance of discriminating benign from malignant masses differs depending 

on the clinical setting in which the mass is initially detected. 

In women who initially present with symptoms, diagnosis of the underlying cause of the 

mass is important since it may help define available treatment options. Although medical 

therapy may relieve symptoms in some cases, surgical management is the treatment of choice for 

many conditions. Because surgery may ultimately be the most appropriate management for 

symptomatic adnexal masses, the main reason to discriminate between benign and malignant 

lesions is to facilitate referral and management by clinicians with specialized training and 

experience in managing ovarian malignancy, with improved outcomes.8-10 

The other main group of women with adnexal masses consists of those without symptoms 

who have a mass detected through either physical examination or imaging. No organization 

currently recommends routine screening with serum markers or imaging for ovarian cancer.11,12 

The U.S. Preventive Services Task Force gives screening (including serum markers, imaging, or 

pelvic examination) a “D” recommendation (fair evidence against screening).13 However, 

because an annual pelvic examination continues to be recommended by professional 

organizations such as the American College of Obstetricians and Gynecologists (ACOG),11,14

many asymptomatic women may have an adnexal mass detected during a periodic health 

maintenance examination. In this setting, discriminating benign from malignant disease is 

important not only to ensure appropriate management in the setting of malignancy, but also to 

avoid unnecessary diagnostic procedures, including surgery, and anxiety in women with 

asymptomatic, nonmalignant conditions. In some cases, there may be a rationale for removing 

certain asymptomatic benign lesions, including prevention of malignant transformation; 

prevention of ovarian torsion (a condition where the ovary twists and occludes its blood supply, 

causing abdominal pain and possibly resulting in loss of ovarian function); prevention of rupture, 

which might lead to acute symptoms or a worse prognosis (for example, in the case of 

endometriosis); prevention of more advanced or complicated surgery for a larger mass or more 

extensive pathologic process after the development of symptoms; and, for premenopausal 

women, possible enhancement of fertility. A review of the evidence (or lack of evidence) 

supporting these rationales is beyond the scope of this report. 

Significance of Clinical Presentation in Evaluation of 

Management Strategies 

 As discussed above, the results of tests used to distinguish benign from malignant disease 

have different implications depending on whether the patient is symptomatic or asymptomatic. 

However, clinical presentation also has implications for interpretation of test results. 

 Diagnostic or screening tests are most commonly characterized by their sensitivity and 

specificity. The sensitivity of a test is the probability that, given the underlying presence of the 

disease, the test result will be positive; 100 percent minus the sensitivity is commonly called the 

false negative rate. The specificity of the test is the probability that, given the underlying 

absence of disease, the test result will be negative; 100 percent minus the specificity is 
14 

commonly called the false positive rate. In an ideal evaluation, the sensitivity and specificity of 

the test are independent of the underlying probability, or prevalence, of disease. 

 Clinically, the more common scenario is that the clinician is aware of the test result and 

needs to know the probability of the presence or absence of disease. In this setting, the positive 

and negative predictive values of the test are more important. 

 The negative predictive value of a test is the probability that, given a negative test result, the 

patient truly does not have disease. It is a function of three parameters: the pretest probability of 

the disease, the sensitivity of the test, and the specificity of test: 

(1 - Prevalence) * Specificity 

[(1 - Prevalence) * Specificity] + [Prevalence * (1 - Sensitivity)] 

As can be seen in the equation, the negative predictive value is much more dependent on test 

sensitivity than test specificity. Negative predictive value will be high when test sensitivity is 

high, and when prevalence is low (i.e., disease is rare). 

 Similarly, the positive predictive value is the probability that, given a positive test result, the 

patient actually has the disease. It is also a function of prevalence, sensitivity, and specificity: 

Prevalence * Sensitivity 

(Prevalence * Sensitivity) + [(1 - Prevalence) * (1 - Specificity)] 

Positive predictive value is high when a test has high specificity, or when prevalence is high 

(disease is common). 

For any given test, the positive predictive value will be higher and the negative predictive 

value lower when used in populations where the disease is common compared to populations 

where the disease is rare, while the positive predictive value will decrease and the negative 

predictive value increase as the disease becomes less common. This effect of prevalence on 

predictive values is independent of test sensitivity and specificity. The significance of the 

prevalence of disease in the population in which test characteristics are being evaluated is even 

more critical because, under some types of study design, disease prevalence can also affect 

estimates of sensitivity and specificity.15

 Therefore, variations in the prevalence of malignancy among women with different clinical 

presentations will affect at least predictive values, and possibly sensitivity and specificity 

estimates. The prevalence of ovarian cancer clearly rises with age, so age and/or menopausal 

status are important considerations in evaluating management strategies in both the symptomatic 

and asymptomatic patient with an adnexal mass. 

 The prevalence of malignancy among asymptomatic women with an adnexal mass will be a 

function of the underlying prevalence or incidence of malignancy and the test characteristics of 

the initial test used to detect the mass. Evaluation of the different screening tests and strategies 

for early detection of ovarian cancer is beyond the scope of this report, especially since there are 

at least three large trials still ongoing.16-18 However, in order to properly interpret the results of 

tests performed in asymptomatic women with pelvic masses, some estimate of the underlying 

probability of malignancy among these women is needed. Since many of these women are likely 

identified through a bimanual pelvic examination, deriving this estimate requires an assessment 

of the sensitivity and specificity of the pelvic examination. Symptomatic patients may be more 

likely to have an underlying adnexal malignancy, especially among postmenopausal women.19 
15 

In any series of women with adnexal masses, the proportion of women who are symptomatic and 

asymptomatic will likely determine the prevalence, and thus the predictive values of the 

diagnostic tests used to evaluate the mass. 

Summary 

In summary, this report focuses on the evidence relevant to establishing the most appropriate 

way to distinguish benign from malignant adnexal masses in both symptomatic and 

asymptomatic women. A key consideration throughout the report will be the underlying 

likelihood of malignancy in the populations studied, and the impact of this prevalence on the 

interpretation of the results of the reviewed studies. The results of this report are intended 

primarily to (a) provide a resource for clinicians and policymakers developing guidelines on 

management of adnexal masses, and (b) provide a resource for researchers and funding agencies 

in identifying gaps in our knowledge and research priorities. 

17

Chapter 2. Methods 

This section of the report describes the basic methodology used to develop the evidence 

report, including topic assessment and refinement, analytic framework, literature search 

strategies and results, literature screening and grading process and criteria, data abstraction and 

analysis methods, and quality control procedures. 

Topic Assessment and Refinement 

The Centers for Disease Control and Prevention (CDC) and the Agency for Healthcare 

Research and Quality (AHRQ) originally identified five key questions to be addressed by the 

report, focused on management of adnexal masses in peri- and postmenopausal women. The 

Duke research team clarified and refined the overall research objectives and key questions by 

first consulting with the two study sponsors, AHRQ and CDC, at which time two questions were 

added, and then by convening a panel of national experts who would serve as advisors to the 

project. These experts were selected to represent relevant specialties including radiology, 

obstetrics-gynecology, and gynecologic oncology, as well as national professional societies, 

including the American College of Obstetricians and Gynecologists (ACOG), the Society of 

Gynecologic Oncologists (SGO) and the American College of Radiology (ACR). Members of 

the technical expert panel were: 

Susan Ascher, MD; Department of Radiology, Georgetown University Hospital; 

Washington, DC (ACR) 

Michael L. Berman, MD; Division of Gynecologic Oncology, UCI Medical Center; 

Orange, CA (SGO) 

Barry B. Goldberg, MD; Department of Radiology, Thomas Jefferson University 

Hospital; Philadelphia., PA (ACR) 

Edward E. Partridge, MD; Department of Obstetrics and Gynecology, University of 

Alabama, Birmingham; Birmingham, AL (American Cancer Society) 

George F. Sawaya, MD; Department of Obstetrics and Gynecology, University of 

California, San Francisco; San Francisco, CA 

 Howard T. Sharp, MD; University of Utah Hospitals and Clinics; Salt Lake City, UT 

 (ACOG) 

 Stanley Zinberg, MD, MS; ACOG; Washington, DC 

As a result of an initial conference call with the technical experts, AHRQ, and CDC, the 

Duke research team modified the key research questions originally proposed in the Task Order in 

two fundamental ways: (1) The questions were expanded to include women of all ages, and (2) 

Question 6 would include laparotomy data, where available. After review of a draft version of 
18

the report by the technical experts and additional reviewers, the order of the questions was also 

changed to allow a more logical flow. 

The key questions addressed by this report are: 

Question 1: What is the prevalence of various tumor types among women with an adnexal 

mass, stratified by cancer status (malignant vs. benign), age, menopausal status, and size of 

tumor? 

 Question 2: What are the sensitivity, specificity, and reproducibility of the bimanual pelvic 

examination? 

Question 3: Among women with a palpable adnexal mass on exam or a mass identified by 

ultrasound/imaging, what is the sensitivity/specificity of various evaluation modalities including 

ultrasound (transvaginal ultrasound, transabdominal ultrasound, color Doppler, two-dimensional 

[2D] vs. three-dimensional [3D] ultrasound), computer tomography (CT) scan, magnetic 

resonance imaging (MRI) scan, and cancer antigen 125 (CA-125) levels for diagnosing 

malignant masses? 

 Question 4: What is the accuracy of explicit scoring systems which incorporate various 

combinations of imaging findings, patient risk factors, and/or CA-125 levels for detecting 

malignancy? Have these scoring systems been applied to a population of women before 

laparoscopy or laparotomy? 

 Question 5: Among women with suspected benign masses on initial investigation, what are 

the sensitivity and specificity of monitoring with periodic CA-125 and/or interval ultrasound 

examinations for detecting malignant masses? How does the interval of testing/definition of 

change affect sensitivity and predictive value? 

Question 6: Among women with adnexal masses, what are the morbidity and mortality from 

diagnostic surgery (laparoscopy or laparotomy)? At what point does the risk of surgery 

outweigh the risk of detecting malignancy? 

 Question 7: What are the estimated trade-offs resulting from various strategies for evaluation 

of the adnexal mass? 

Analytic Framework 

Based on the original proposal and discussions with CDC, AHRQ, and the technical expert 

panel, we developed the following analytic framework to structure our review and synthesis 

(Figure 2). 
19

Figure 2. Analytic framework for evidence report (numbers refer to key questions) 

Adnexal Mass

Symptoms

Asymptomatic

Suspected

Benign Mass

Suspected

Malignancy

Confirmed

Malignancy

False Positive

False Negative

Confirmed

Benign Mass

Cost &

Utilization

Morbidity

Mortality

Symptoms

QOL

Premenopausal

Women

Postmenopausal

women

PelvicExam

Imaging

Imaging

or

biomarker

Scoring

System

F/U

Testing

Harms of

diagnostic

surgery

2

7

1 3

4

56
20

Comments on this analytic framework are as follows: 

• Separate consideration of age or menopausal status is important, since several factors that 

may affect the probability that a given adnexal mass is malignant may vary with age 

and/or menopausal status: the underlying incidence of various conditions that result in an 

adnexal mass, the frequency of contact with clinicians, the type and length of followup, 

and the prevalence of other conditions that may cause symptoms similar to those caused 

by ovarian malignancy or other symptomatic pelvic pathology. Race/ethnicity may also 

play a role, both in the relative likelihood of malignancy and the likelihood of other 

conditions and contact with clinicians. 

• A variety of conditions, both benign and malignant, can cause a mass in the adnexa. The 

underlying prevalence of each type of condition, along with the sensitivity and specificity 

of the initial diagnostic test, will determine the proportion of patients with a given test 

result who are truly disease-free, or who truly have disease. The evidence on the 

prevalence of these conditions is reviewed in Question 1. 

• Women can present with an adnexal mass in one of two ways – through presentation with 

symptoms and subsequent detection of a mass through a physical examination, or through 

detection of a mass in an asymptomatic woman during physical examination or an 

imaging study. The ultimate probability of malignancy may vary based on how an 

adnexal mass is initially detected, since the prevalence of malignancy at this stage will 

drive the positive and negative predictive values of all subsequent tests. Because many 

women will initially have their masses detected through a bimanual pelvic examination, 

we review the evidence on the sensitivity and specificity of this component of the 

physical examination in Question 2. 

• After the initial diagnosis of an adnexal mass, the choice of the next test will provide a 

revised estimate of the probability of a given disease. Although determining this 

probability is important in the symptomatic patient so that she may receive appropriate 

therapy, it is even more important in the asymptomatic patient, who runs the risk of 

undergoing unnecessary surgery for a benign condition if the test is falsely positive. 

Question 3 addresses the sensitivity and specificity of tests commonly used as “next step” 

diagnostic procedures. 

• Frequently, a combination of various test results and patient characteristics can provide 

better discrimination between diseased and non-diseased, or benign and malignant, than 

any single test parameter. Question 4 addresses the performance of various multivariate 

scoring systems in discriminating benign from malignant masses. 

• Because 100 percent sensitivity is difficult to achieve, some tests will be falsely negative. 

One strategy to minimize the consequences of a false negative test would be to monitor 

the patient with a specified test or tests, at a specified frequency, for a specified duration. 

Question 5 addresses the evidence for the effectiveness of such an approach, and which 

combination of test, test frequency, and duration of followup offers optimal performance. 

• The ultimate diagnosis of ovarian malignancy requires surgical exploration, either 

through laparoscopy or laparotomy. Although an adverse outcome of surgery is not 

desirable under any circumstances, patients who undergo surgery because of a 

symptomatic mass have the possibility of improvement in symptoms, while, for patients 

who ultimately prove to have an ovarian malignancy, surgical management with adequate 

staging and reduction in tumor bulk appears to improve outcomes. However, for patients 
21

with some asymptomatic benign masses, the benefits of surgery may be less clear while 

providing substantial risks. Question 6 addresses the risks of diagnostic surgery, both 

laparoscopy and laparotomy, for women with adnexal masses. 

• Finally, estimating the benefits, harms, and costs of various management strategies, 

including screening, for ovarian cancer is complex. Synthesizing the wide range of data 

and incorporating uncertainty, as well as missing data, can often be done using simulation 

models. Question 7 presents an initial attempt at summarizing the likely outcomes of 

several different diagnostic strategies. Because modeling the natural history of ovarian 

cancer will ultimately be important for comprehensive analyses of different screening and 

diagnostic strategies, we also review existing models for the natural history of ovarian 

cancer with special attention paid to underlying assumptions. 

Literature Search and Review 

Sources 

The primary sources of literature were MEDLINE® (1966-September 2004) and the 

Cochrane Database of Systematic Reviews. Searches of these databases were supplemented by 

reviews of reference lists contained in all included articles and in relevant review articles and 

meta-analyses. 

Search Strategies 

The basic search strategy used the National Library of Medicine’s Medical Subject Headings 

(MeSH) key word nomenclature developed for MEDLINE® and was adapted for use in the other 

databases. The searches were limited to the English language. The texts of the three major 

search strategies are given in Appendix A.* The searches yielded a total of 677 citations, whose 

records are maintained in a ProCite20 database. 

Abstract and Full-text Screening 

Paired researchers from the Duke research team independently reviewed a set of abstracts 

and classified each as “include” or “exclude” according to study-specific criteria, which they 

developed. An abstract was included if at least one of the paired reviewers recommended that it 

be included. A total of 445 abstracts were included for the further “full-text review” stage. 

Interrater reliability for include/exclude decisions was tested by having 10 pairs of readers 

review 138 abstracts. Agreement was good to excellent (kappa 0.66 to 0.95). 

At the full-text review stage, the paired researchers independently reviewed a set of the 

articles, and indicated a decision to “include” or “exclude” the article for the data abstraction 

stage. When a pair of reviewers arrived at a different opinion about whether to include an 

article, they were asked to reconcile the difference. Detailed inclusion and exclusion screening 

criteria were developed by research question and are listed below. 

 

* Appendixes cited in this report are provided electronically at 

http://www.ahrq.gov/downloads/pub/evidence/pdf/adnexal/adnexal.pdf.
22

Full-text Screening Criteria 

Initially, the patient population was limited to peri- and postmenopausal women, and only 

articles that provided data specifically by age or menopausal status were included. After initial 

discussion with the expert panel, the search was expanded to include premenopausal women. 

Question 1. Background clarifications were as follows: 

(1) The search should be limited to (a) screening studies and (b) case series of women 

with an undiagnosed mass (not just women who went to laparoscopy/path diagnosis). 

(2) Pathology list: 

a. Benign 

 i. Uterine leiomyoma 

 ii. Nonneoplastic cysts, such as: 

 1. Follicular (functional) cysts 

 2. Corpus luteal (functional) cysts 

 3. Theca lutein cysts 

 4. Simple cysts 

 5. Peritoneal inclusion cysts 

 6. Paraovarian cysts 

 7. Hemorrhagic cysts 

 8. Endometrial cyst 

 iii. Polycystic ovary disease 

 iv. Cystic teratoma (dermoid cyst) 

 v. Hydrosalpinx, 

 vi. Cystadenoma 

 vii. Fibroma 

b. Malignant ovarian neoplasms 

 i. Adenocarcinoma 

 ii. Others 

c. Tumors of low malignant potential 

Screening criteria for Question 1 were: 

(1) undiagnosed mass (regardless of whether symptomatic or asymptomatic; detected by 

palpation or ultrasound imaging); 

(2) exclude if n < 50; if n ≥ 50, write n on decision sheets; 

(3) histology diagnosis; 

(4) screened women without mass (case series or cohort) or women with adnexal mass 

(case series). 

Question 2. Screening criteria were as follows: 

(1) comparison of bimanual pelvic examination to a reference standard; 

(2) n > 20; 

(3) able to construct 2-by-2 table for test characteristics. 

Question 3. Screening criteria were as follows: 

(1) undiagnosed mass (regardless of whether symptomatic or asymptomatic; detected by 

palpation or ultrasound imaging) or screening population; 

(2) disease status distinguishes malignant from non-malignant; 

(3) must have 20 or more subjects; 
23

(4) disease status must be verified by histology or negative surgery 

(laparoscopy/laparotomy); 

(5) test is ultrasound, CT, MRI, PET, serum CA-125, or bimanual pelvic exam; 

(6) able to construct 2-by-2 table for test characteristics. 

Question 4. Screening criteria were as follows: 

(1) patients with cancer; 

(2) studies with scoring, risk score, combined modality approach; 

(3) assesses predictive value of two or more variables (radiographic, patient 

characteristics or CA-125) using multivariable model; 

(4) screening studies; 

(5) n ≥ 50. 

Question 5. Screening criteria were as follows: 

(1) n ≥ 50; 

(2) histology or followup interval = at least 9 months; 

(3) outcome = continued negative test with no clinical evidence of developing ovarian 

cancer. 

Question 6. Screening criteria were as follows: 

(1) procedure = operative laparoscopy for adnexal mass, with or without biopsy; 

(2) addresses complications of procedure (morbidity or mortality); 

(3) n ≥ 100 for morbidity. 

Question 7. Screening criterion was as follows: article described mathematical or computer 

model of natural history of ovarian cancer. 

 Summaries of the results of the abstract screening and full-text review are provided in Tables 

2 and 3. A list of excluded articles by reason for exclusion is found in Appendix B.*

Table 2. Results of abstract screening and full-text review 

Articles identified 1,023 

 

Abstracts reviewed 1,023 

 Included 445 

 Excluded 578 

 

Full-text articles reviewed 445†

 Included 204 

 Excluded 269 

† The combined number of included (204) and excluded (269) articles exceeds the total 445 reviewed at the full-text 

level because 28 articles were considered excluded for one question, but included for another question. 

 

* Appendixes cited in this report are provided electronically at 

http://www.ahrq.gov/downloads/pub/evidence/pdf/ adnexal/adnexal.pdf.
24

Table 3. Included full-text articles by research question 

Question Number of articles 

Question 1: Prevalence of tumor types 20 

Question 2: Bimanual pelvic examination 14 

Question 3: Single modality tests 153 

Question 4: Explicit scoring systems 36 

Question 5: Monitoring women with suspected benign masses 9 

Question 6: Surgical morbidity and mortality 24 

Question 7: Modeling diagnostic strategies 4 

Total number of included articles 204†

† Some articles were included for more than one question.

Data Abstraction and Development 

of Evidence Tables 

The Duke research team developed and piloted evidence table formats for abstracting data to 

answer each of the seven research questions (see Appendix C*). Based on clinical expertise, a 

pair of researchers was assigned to one of the seven research questions to abstract the data from 

the eligible articles. One of the paired researchers abstracted the data into the evidence tables, 

and the second researcher over-read the article and accompanying evidence table to check for 

accuracy and completeness. The completed evidence tables are provided in Appendix D.* 

Quality Assessment Criteria 

At the data abstraction stage, the researcher was asked to evaluate each included article for 

factors affecting internal and external validity. The quality assessment criteria varied by 

question and are listed below. Researchers were instructed to assign a + or - to each item, and 

provide a brief rationale for each decision. 

Quality criteria were as follows: 

Question 1: What is the prevalence of various tumor types among women with an adnexal 

mass, stratified by cancer status (malignant vs. benign), age, menopausal status, and size of 

tumor? 

• Size of population from which sample drawn. Rationale: Ideally, data on prevalence 

would come from population-based studies; alternatively, a precise description of the 

population served by a given center (for case series) allows comparison to other studies. 

Credit given for description. 

• Number of cases. Rationale: Small numbers, especially in the denominator, decrease the 

precision of the estimate of proportion/prevalence. 

• Patient selection. Rationale: The process by which patients come to undergo surgery 

may affect the prevalence of underlying disease, or the proportion of different types. For 

example, if one group of patients was more likely to undergo medical treatment for 

certain types of adnexal findings (such as oral contraceptives for possible functional 

 

* Appendixes cited in this report are provided electronically at 

http://www.ahrq.gov/downloads/pub/evidence/pdf/ adnexal/adnexal.pdf.
25

cysts), the distribution of types of masses would be different than in a group less likely to 

undergo medical therapy prior to surgery. Studies were given credit if this process were 

described. 

• Application of reference standard. Rationale: If either all or a random sample of test 

negative subjects do not undergo the reference standard test, significant overestimation of 

test sensitivity can occur. Studies given credit if all patients underwent reference 

standard; alternative standards (such as pre-defined followup) were allowed for screening 

studies.15,21

Question 2: What are the sensitivity, specificity, and reliability of the bimanual pelvic 

examination?

• Reference standard. Rationale: Histology or, at the least, intraoperative visualization, is 

the recognized reference standard for ovarian or other adnexal pathology. Studies given 

credit if all subjects underwent this reference standard (documented followup acceptable 

in screening studies). 

• Verification bias. Rationale: If either all or a random sample of test negative subjects do 

not undergo the reference standard test, significant overestimation of test sensitivity can 

occur. Studies given credit if all patients underwent reference standard; alternative 

standards (such as predefined followup) were allowed for screening studies. 

• Test reliability/variability. Rationale: Inter- and intraobserver variability can, at least, 

affect the precision of estimates of test characteristics (if random), or can bias results in 

one direction or the other (if systematic). Studies given credit if test reliability/variability 

were measured, other studies measuring it were referenced, or if it was discussed as an 

issue. 

• Sample size. Rationale: Small sample sizes limit the precision of estimates, particularly 

for test characteristics, which are proportions. Studies given credit if sample size 

discussed, or if study over 100 subjects. 

• Statistical tests. Rationale: Inappropriate use of statistical tests (e.g., use of parametric 

tests for nonparametric data) or inappropriate interpretation of results (concluding no 

difference for underpowered studies) can lead to invalid conclusions about a study. 

Studies given credit if no examples of inappropriate use identified. 

• Blinding. Rationale: Awareness of other relevant information (such as clinical history 

or, in the case of retrospective studies where images are reviewed outside of the clinical 

setting, the ultimate diagnosis) can lead to biased interpretation of results. Studies given 

credit if blinding explicitly described. 

• Definition of +/- on screening test. Rationale: The ability to replicate a study, or to 

compare results between studies, depends on a description of the criteria for defining a 

positive test. Studies given credit if definition provided, or reference for definition 

provided. 

Question 3: Among women with a palpable adnexal mass on exam or a mass identified by 

ultrasound/imaging, what is the sensitivity/specificity of various evaluation modalities including 

ultrasound (transvaginal ultrasound, transabdominal ultrasound, color Doppler, 2D vs. 3D 

ultrasound), CT scan, MRI scan, and CA-125 levels for diagnosing malignant masses? 

• Reference standard 

• Verification bias 

• Test reliability/variability 

• Sample size 
26

• Statistical tests 

• Blinding 

• Definition of +/- on screening test 

Rationale for these criteria is the same as for Question 2. 

Question 4: What is the accuracy of explicit scoring systems which incorporate various 

combinations of imaging findings, patient risk factors, and/or CA-125 levels for detecting 

malignancy? Have these scoring systems been applied to a population of women before 

laparoscopy or laparotomy? 

• Reference standard. Rationale: Histology or, at the least, intraoperative visualization, is 

the recognized reference standard for ovarian or other adnexal pathology. Studies given 

credit if all subjects underwent this reference standard (documented followup acceptable 

in screening studies). 

• Verification bias. Rationale: If either all or a random sample of test negative subjects do 

not undergo the reference standard test, significant overestimation of test sensitivity can 

occur. Studies given credit if all patients underwent reference standard; alternative 

standards (such as pre-defined followup) were allowed for screening studies. 

• Test reliability/variability. Rationale: Inter- and intra-observer variability can, at least, 

affect the precision of estimates of test characteristics (if random), or can bias results in 

one direction or the other (if systematic). Studies given credit if test reliability/variability 

were measured, other studies measuring it were referenced, or if it was discussed as an 

issue. 

• Sample size. Rationale: Small sample sizes limit the precision of estimates, particularly 

for test characteristics, which are proportions. In the setting of multivariate models, study 

power is limited by the number of cases in the data set. Studies given credit if sample 

size discussed. 

• Statistical tests. Rationale: Inappropriate use of statistical tests (e.g., use of parametric 

tests for nonparametric data) or inappropriate interpretation of results (concluding no 

difference for underpowered studies) can lead to invalid conclusions about a study. 

Studies given credit if no examples of inappropriate use identified. 

• Blinding. Rationale: Awareness of other relevant information (such as clinical history 

or, in the case of retrospective studies where images are reviewed outside of the clinical 

setting, the ultimate diagnosis) can lead to biased interpretation of results. Studies given 

credit if blinding explicitly described. 

• Definition of +/- on screening test. Rationale: The ability to replicate a study, or to 

compare results between studies, depends on a description of the criteria for defining a 

positive test. Studies given credit if definition provided, or reference for definition 

provided. 

• Explicit validation method. Rationale: A scoring system will often perform differently 

when tested in a data set other than the one in which it was developed. Studies given 

credit if the method for validating the system was explicitly described or referenced. 

Question 5: Among women with suspected benign masses on initial investigation, what are 

the sensitivity and specificity of monitoring with periodic CA-125 and/or interval ultrasound 

examinations for detecting malignant masses? How does the interval of testing/definition of 

change affect sensitivity and predictive value? 

• Reference standard 

• Verification bias 
27

• Test reliability/variability 

• Sample size 

• Statistical tests 

• Blinding 

• Definition of +/- on screening test 

Rationale for these criteria is the same as for Question 2. 

Question 6: Among women with adnexal masses, what are the morbidity and mortality from 

diagnostic surgery (laparoscopy or laparotomy)? At what point does the risk of surgery 

outweigh the risk of detecting malignancy? 

• Size of population from which sample drawn 

• Number of cases 

• Patient selection 

• Application of reference standard 

Rationale for these criteria is the same as for Question 1. 

Question 7: What are the estimated trade-offs resulting from various strategies for evaluation 

of the adnexal mass? 

For this question, we examined published models of ovarian cancer and qualitatively 

assessed the underlying assumptions and evidence for them. 

Additional Analyses 

Test Characteristics and Confidence Intervals 

For test characteristics, a Microsoft Excel® spreadsheet was developed which calculated 

appropriate test characteristics (sensitivity, specificity, negative predictive value, positive 

predictive value) for individual studies if studies provided enough data to input (a) values for 

individual cells of a 2-by-2 table, (b) the prevalence of disease and values for sensitivity and 

specificity, or (c) sufficient data to solve for two equations involving sensitivity, specificity, or 

predictive values. Ninety-five percent confidence intervals were automatically estimated using 

the approximate formula for proportions: 

p ± 1.96* p * (1− p)/ N , where p = point estimate of proportion, N = total sample size. 

Prevalence and Event Rates and Confidence Intervals 

For Questions 3 and 6, prevalence of different mass types, and morbidity and mortality rates, 

were also calculated using the above formula. For studies where the numerator of a particular 

proportion was 0, the upper bound was estimated using the formula: 

p + 2.56* p * (1− p)/ N , where p = 2/(N + 2). 
28

Estimation of Pooled Sensitivity and Specificity 

For Questions 2, 3, and 4, we used two complementary methods for assessing diagnostic test 

performance: (1) summary receiver operating characteristic (ROC) analysis; and (2) 

independently combined sensitivity and specificity values. We calculated pooled sensitivity and 

specificity estimates, along with 95 percent confidence intervals and summary ROC curves, 

using Meta-Stat 0.6, a shareware program for performing meta-analyses of diagnostic tests.22 In 

this software, logits of sensitivity and specificity values are pooled, using a random-effects 

model weighted by the inverse of the variance.23

We combined the sensitivity and specificity values of the tests across studies using a randomeffects model to estimate the average values. A random-effects model incorporates both the 

within-study variation (sampling error) and between-study variation (true treatment-effect 

differences) into the overall treatment estimate. It gives a wider confidence interval than the 

fixed-effect model (which considers only within-study variability) when estimates are based on 

heterogeneous results. 

When each is combined separately, sensitivity and specificity tend to underestimate the true 

test sensitivity and specificity; however, they can provide an indication of the approximate test 

operating point for most of the studies. 

Summary ROC curves are a potentially useful graphical summary of the diagnostic test 

performance data. In brief, each study provides a pair of sensitivity and specificity values to the 

analysis. After logistic transformation of data, a linear model is fitted to the observed studies 

using regression analysis. This best-fit model can then be transformed back to ROC space and 

plotted as curve. A summary ROC curve can be thought of as an ROC curve that describes joint 

changes in sensitivity and specificity with changes in cutoff values. The ideal position of an 

ROC curve is near the upper left corner. The area under the curve (AUC) is another summary 

measure of the degree of discrimination of a test. 

The summary ROC method assumes that the variability in the reported sensitivity and 

specificity values from different studies is due to different cutoff values (explicit or implicit) 

being applied.24 However, the summary ROC curve can summarize studies whose variability 

may be due to other sources of variation, since the summary ROC curve no longer ties specific 

cutoff values to specific intervals of the curve. One can think of a summary ROC curve as an 

overall estimate of the discrimination ability of a test. 

When there is little variability in the test results – i.e., when studies appear to be operating at 

similar thresholds and report similar results – summary ROC analysis provides little additional 

information. In this case, separately averaged sensitivity and specificity values across studies 

will give similarly useful summary information. However, where there is substantial variability 

in test results, the separately averaged sensitivity and specificity values tend to have wide 

confidence intervals and have means that do not characterize any of the studies. In this case, 

SROC curves provide a more suitable analysis framework. 

Estimates of National Rates of Surgery for Adnexal Mass 

The Nationwide Inpatient Sample (NIS) is a public access database maintained by AHRQ. 

The NIS represents a stratified sample of approximately 20 percent of all discharges from U.S. 

hospitals; data for the year 2000 contain administrative discharge data from hospitals in 28 

states, while 2001 contains data from 33 states.25 Weights are provided in order to allow 
29

estimation of national data based on this sample. We used data from 2000 and 2001 to provide 

supplemental data on the frequency of diagnostic laparoscopy and exploratory laparotomy for 

Question 6. Because previous work has shown that administrative data may lack sufficient 

clinical detail to compare outcomes,26 we did not attempt to directly compare complication rates 

between these procedures, or between diagnoses. 

The search was limited to women 15 years and older, who had one of the following 

International Classification of Diseases, Ninth Revision (ICD-9) diagnostic codes: 183.x 

(malignant neoplasm of the ovary and other uterine adnexa), 220.x (benign neoplasms of the 

ovary); 620.x (ovarian cysts); 752.11 (para-ovarian cysts); 614.0, 614.1, 614.2, 614.6 (adnexal 

masses secondary to pelvic inflammatory disease); 789.33, 789.34, 789.39 (abdominal masses 

arising in the left or right lower quadrant, or other nonspecified site); and V655 (normal findings 

after diagnostic evaluation). 

In order to avoid overestimation of complication rates due to other procedures, we then 

excluded patients who had an ICD-9 diagnosis code for hysterectomy (68.x). Procedures were 

then classified as laparoscopy only (54.21), laparoscopy with conservative ovarian surgery 

(65.3x, 65.4x, 65.5x, 65.6x), laparoscopy with oophorectomy (65.0x, 65.2x), or laparotomy 

(54.11) alone, with conservative ovarian surgery (same codes), or with oophorectomy (same 

codes). 

A discharge status of “Dead” indicated in-hospital mortality. Complications of surgery or 

hospitalization were indicated by diagnosis codes of E870 through E876. 

Model of Natural History of Ovarian Cancer 

We used a Markov state-transition model to explore the impact of alternate assumptions 

about the natural history of ovarian cancer. The original model was developed as a graduate 

school project by Karen Hoffman, MD, and further refined in collaboration with two of the 

authors of this report (Drs. Kulasingam and Myers). 

 The model simulates a cohort beginning at age 40 distributed across cancer stages. Subjects 

progress from no cancer through the stages of ovarian cancer to death. Each cycle is 12 months 

long. The original model design is illustrated in Figure 3; subsequent modifications include 

removal from the at-risk population by undergoing oophorectomy for another cause, and 

allowing some Stage I cancers the possibility of progressing directly to Stage III. Model 

variables and the ranges over which they were varied are outlined in Table 4. Probability of 

progressing from no cancer to Stage I cancer varies by age and is based on age-adjusted ovarian 

cancer incidence rates. Because the probability of progression (or duration of time within a 

stage) is unknown, probability of progression from Stage I to II, from Stage II to III, and from 

Stage III to Stage IV was adjusted to reflect incidence distribution across stages. Within the 

model, subjects may die from causes other than ovarian cancer. The probability of dying from a 

cause other than ovarian cancer varies by age and was constructed from CDC National Vital 

Statistics reports and Surveillance, Epidemiology, and End Results (SEER) data.27,28 Probability 

of clinical diagnosis is based on the annual report of the International Federation of Gynecology 

and Obstetrics (FIGO).29 Five-year survival rates gathered by SEER 1992-98 were used to 

predict probability of dying from ovarian cancer.27 SEER localized disease corresponds to Stage 

I cancer, regional disease corresponds to Stage II cancer, and distant disease corresponds to 

Stage III/IV ovarian cancer. The model was constructed in DATA 4.0.30
30

Figure 3. Schematic of natural history model 

DeadOtherCause

MortCaAdj[Age]

DeadOtherCause

Cancer Survivor

# Cancer Survivor

Cancer Survivor

0

DeadLap

0

DeadOtherCause

0

DeadCancer

0

LaporotomyDeath

pLapDeath DeadLap

Survive

# Cancer Survivor

DieOvarianCancer

pDieStageIV DeadCancer

SurvivorStageIV

#

ClinicallyDiagnosed

pClinDxStageIV

StageIV

# StageIV

Dead

pStageIVtoDead DeadCancer

ClinicallyMissed

#

Alive

#

DeadOtherCause

MortCaAdj[Age]

DeadOtherCause

StageIV

2.93396E-05

LaporotomyDeath

pLapDeath DeadLap

Survive

# Cancer Survivor

DieOvarianCancer

pDieStageIII

DeadCancer

SurvivorStageIII

#

ClinicallyDiagnosed

pClinDxStageIII

StageIII

# StageIII

StageIV

pStageIIItoStageIV StageIV

ClinicallyMissed

#

Alive

#

DeadOtherCause

MortCaAdj[Age]

DeadOtherCause

StageIII

9.98248E-05

LaporotomyDeath

pLapDeath DeadLap

Survive

# Cancer Survivor

DieOvarianCancer

pDieStageII

DeadCancer

SurvivorStageII

#

ClinicallyDiagnosed

pClinDxStageII 

StageII

# StageII

StageIII

pStageIItoStageIII StageIII

ClinicallyMissed

#

Alive

#

DeadOtherCause

MortCaAdj[Age]

DeadOtherCause

StageII

0.000151352

LaporotomyDeath

pLapDeath DeadLap

Survive

# Cancer Survivor

DieOvarianCancer

pDieStageI

DeadCancer

SurvivorStageI

#

ClinicallyDiagnosed

pClinDxStageI

StageI

# StageI

StageII

pStageItoStageII StageII

ClinicallyMissed

#

Alive

#

DeadOtherCause

MortCaAdj[Age]

DeadOtherCause

StageI

0.000187902

No Cancer

# NoCancer

StageI

tCompInc[Age] StageI

Alive

#

DeadOtherCause

MortCaAdj[Age] DeadOtherCause

NoCancer

0.999531581

No Screen

Age=StartAge+_stage

Abbreviations for probabilities are described in Table 4, below. 
31

Table 4. Model variables 

Variable description Model abbreviation of 

variable 

Value Range 

varied 

pClinDxStageI 0.261 

pClinDxStageII 0.446 

pClinDxStageIII 0.837 

Probability of clinical diagnosis for each stage (I, II, III, or IV) if 

no screening test or if screening produces a false negative 

pClinDxStageIV 0.950 

Calibrated 

Probability of dying from diagnostic exploratory laporotomy pLapDeath 0.00023 0.00 to 

0.0010 

pDieStageI 

 0.051 

Not varied 

pDieStageII 

0.187 

Not varied 

pDieStageIII 

0.691 

Not varied 

Probability of dying from each stage of cancer, based on 5-

year survival rates 

pDieStageIV 

 0.691 

Not varied 

Probability of developing Stage I cancer, based on ovarian 

cancer incidence rates 

tCompInc Varies with 

age 

Probability of dying from a cause other than ovarian cancer tMortCaAdj Varies with 

age 

Peer Review Process 

We employed internal and external quality-monitoring checks through every phase of the 

study to reduce bias, enhance consistency, and verify accuracy. Examples of internal monitoring 

procedures include: three progressively stricter screening opportunities for each article (abstract 

screening, full-text article review, data abstraction review); involvement of three individuals 

(two clinicians and copy editor) in each data abstraction; agreement of at least two clinicians on 

all included studies. 

Our principle external quality-monitoring device was the peer-review process. Nominations 

for peer reviewers were solicited from several sources, including a technical expert panel and 

interested federal agencies. The list of nominees was forwarded to the Agency for Healthcare 

Research and Quality (AHRQ) for vetting and approval. A final list of peer reviewers is 

provided in Appendix E.*

 

* Appendixes cited in this report are provided electronically at 

http://www.ahrq.gov/downloads/pub/evidence/pdf/ adnexal/adnexal.pdf.

33

Chapter 3. Results 

Question 1: Prevalence of Tumor Types 

Question 1 is: What is the prevalence of various tumor types among women with an adnexal 

mass, stratified by cancer status (malignant vs. benign), age, menopausal status, and size of 

tumor? 

 

Approach 

We included studies in the U.S. population with more than 50 women and limited the 

literature search to screening studies and case series where results were provided for all women 

with an undiagnosed mass, not just those with subsequent positive additional tests.21 Studies of 

adnexal mass in which the gold standard is applied only to those with positive tests results would 

underestimate the prevalence of disease and cause a substantial bias. 

Results 

Twenty articles met the inclusion criteria and are described in the Evidence Table 1 

(Appendix D*).31-50

Detailed prevalences for specific tumor types are provided in Evidence Table 1. The 

included studies can be divided into two groups. The first group includes four reports from a 

large screening study in Kentucky (Table 5). The prevalence of malignancy ranged from 0.09 to 

0.18 percent. In postmenopausal women, the prevalence of malignancy was 0.09 to 0.18 percent, 

borderline tumors were not reported, and the prevalence of benign tumors was 0.08 to 1.3 

percent. In a population that included either postmenopausal women or those with a family 

history of breast, ovarian, or colorectal cancer, the prevalence of malignancy was 0.10 to 0.11 

percent, of borderline tumors 0.02 percent, and of benign tumors 1.1 to 1.2 percent. 

The most common malignant tumor types include primary ovarian carcinoma, such as serous 

and mucinous cystadenocarcinoma, granulosa cell tumors, and undifferentiated adenocarcinoma. 

Borderline tumors were less common, such as serous low malignant potential (0.02 percent). 

The most common benign tumors were serous cystadenoma (0.4 to 0.7 percent), paratubal cyst 

(0.1 to 0.16 percent), endometrioma (0.03 to 0.3 percent), and mature teratoma (0.02 to 0.08 

percent). 

 

* Appendixes cited in this report are provided electronically at 

http://www.ahrq.gov/downloads/pub/evidence/pdf/ adnexal/adnexal.pdf.
34

Table 5. Prevalence of tumor types in screening studies* 

Study N % Menopausal Malignant Borderline Benign 

DePriest et 

al.,199336 3,220 100; most had 

positive family history 

of breast, ovarian, or 

colorectal cancer 

0.09% Not reported 1.3% 

DePriest et 

al.,199734 6,470 Either menopausal or 

had positive family 

history of breast 

(30%), ovarian (24%), 

or colorectal cancer 

(15%) 

0.11% Not reported 1.2% 

Modesitt et al., 

200340 15,106 100 0.18% Not reported 0.8% 

Van Nagell et al., 

200049 14,469 Either menopausal or 

had positive family 

history of breast 

(34%), ovarian (23%), 

or colorectal cancer 

(23%) 

0.1% 0.02% 1.1% 

*Note: All four publications represent the same screening study at different times.

The majority of U.S. studies with histological diagnosis of all masses (n = 16) were case 

series of women with undiagnosed adnexal mass undergoing laparotomy (Table 6). The 

prevalence of malignancy ranged from 5.7 to 57.5 percent, the range of borderline tumors was 

1.4 to 11.2 percent, and the prevalence of benign tumors was 40 to 100 percent. All tumor types 

were over-represented because patients had an undiagnosed adnexal mass, and the clinical 

presentation was not well described in the majority of studies. Most studies included both 

premenopausal women and postmenopausal women and did not provide results separately. The 

one study that included only postmenopausal women41 found only benign tumors. 

Table 6. Case series and retrospective medical record reviews 

Study Denominator Location Age, 

menopausal 

status, race 

Malignant Borderline Benign 

Childers et 

al.,199632 138 AZ 52 13.8% Not reported 86.2% 

Dottino et 

al.,199937 160 NY 52.2 

53% post 

91% white 

8.1% 5% 86.9% 

Fleischer et al., 

199638 62 TN 50 

>50% post 

50% Not reported 50% 

Lin et al., 

199339 80 NY 56 

76% post 

90% white 

57.5% 2.5% 40% 

Parker et al., 

199441 61 Multi-site 65 

100% post 

None None 100% 

Roman et al., 

199742 226 CA 20% post 11.5% 7.5% 81% 

Schneider et 

al., 199343 55 AZ 53 

60% post 

25.5% 3.6% 70.9% 
35

Study Denominator Location Age, 

menopausal 

status, race 

Malignant Borderline Benign 

Scoutt et al., 

199444 109 CT 40 20.2% Not reported 79.8% 

Shen-Gunther 

et al., 200245 125 OK/NV 58 

82% white 

44.8% 9.6% 45.6% 

Smikle et al., 

199546 195 TX 40% post 13.3% Not reported 86.7% 

*Chalas et al., 

199231 241 NY Not reported 50.2% 7.5% 42.3% 

Cohen et al., 

200133 71 IL 22-80 

44% post 

18.3% 1.4% 80.3% 

DePriest et al., 

199335 121 KY 3-74 

49% post 

10.7% Not reported 89.3% 

Troiano, 199747 144 CT 45 

29% post 

11.8% 2.1% 86.1% 

Twickler et al., 

199948 244 TX 38.6 5.7% 6.6% 87.7% 

Vasilev et al., 

198850 182 CA Not reported 8.2% 1.6% 90.1% 

*Retrospective chart review

Discussion 

Estimating the age-specific prevalence of specific adnexal tumor types from the available 

literature is difficult. The best data come from a series of reports from a large screening study; 

overall prevalence of masses was 1 to 2 percent, with benign masses outnumbering malignant by 

4- to 10-fold. Because patients with negative screening test results did not undergo definitive 

diagnostic procedures in these studies, the prevalence estimates are dependent on the sensitivity 

of the screening tests used (and the completeness of followup among test negatives). In addition, 

there is a potential bias in that premenopausal women enrolling in the screening study were at 

higher risk than average because of family history; in addition, postmenopausal women may 

have been more likely to enroll because of concerns based on family history, vague symptoms, 

or other reasons which would affect relative prevalence compared to the general population. 

Estimates of prevalence in studies with 100 percent histologic diagnosis are inevitably biased 

by the clinical factors that determine which patients ultimately undergo surgery. These can 

include the presence and nature of symptoms (patients with symptoms referable to a mass would 

likely undergo surgery sooner than those with asymptomatic masses, all other things being 

equal); other findings (for example, the presence of ascites); patient anxiety; the diagnostic 

algorithms used (for example, the duration of followup for persistence); and the nature of the 

practice (malignancies will be more frequent in a gynecologic oncology practice compared to a 

general gynecology practice). 

As mentioned previously, we did not include studies from outside the United States. Given 

differences in ethnic backgrounds (affecting genetic risks), observed differences in cancer 

incidence, and differences in clinical practice between countries, and the almost universal failure 

of studies to describe the clinical history leading to the diagnosis of adnexal mass, inclusion of 

these studies would not have allowed a more precise estimate of prevalence of different types of 

adnexal masses in the U.S. population. 
36

Summary 

In four reports from a large U.S. screening study, the prevalence of adnexal masses detected 

by ultrasound among postmenopausal women was 0.8 to 1.3 percent, and the prevalence of 

malignancy 0.09 to 0.18 percent (i.e., 9 to 18 per 10,000). Prevalence of different pathologies 

varies widely among case series. There are no data on the relative prevalence of different 

pathologies among women with asymptomatic masses compared to women with symptomatic 

masses. 

Question 2: Bimanual Pelvic Examination 

Question 2 is: What are the sensitivity, specificity, and reliability of the bimanual pelvic 

examination? 

Approach 

Articles were sought which evaluated the ability of the bimanual examination to detect 

adnexal masses, and/or to discriminate benign from malignant masses. Preference was given to 

studies where there was histological confirmation of the diagnosis, but an alternative reference 

standard (such as followup) was allowed for screening studies. Data allowing calculation of 

sensitivity and specificity had to be provided. 

Our rationale for including the pelvic examination was based on its role in the initial 

evaluation of adnexal masses. Some asymptomatic women will have a mass detected as part of a 

“routine” physical examination; others will have a mass detected as part of an examination 

performed because of symptoms. The postexamination probability of malignancy is a function 

of the prevalence of cancer and the sensitivity and specificity of the bimanual examination; these 

probabilities, in turn, will affect the positive and negative predictive values of additional tests 

such as cancer antigen 125 (CA-125) and imaging studies. Because the pelvic examination will 

be the first test performed, either as a screening test or as a diagnostic test, knowledge of its test 

characteristics is important for evaluating subsequent diagnostic tests. 

Results of Literature Search and Screening 

We identified 14 studies that met the inclusion criteria.42,51-63 Nine studies provided data on 

discrimination between benign and malignant masses,42,51,53-57,62,63, four on the ability of the 

bimanual examination to detect any adnexal mass,52,59-61 and one provided data on both 

discrimination between benign and malignant and ability to detect masses.58 All 14 studies are 

summarized in Evidence Table 2 (Appendix D*). 

 

* Appendixes cited in this report are provided electronically at 

http://www.ahrq.gov/downloads/pub/evidence/pdf/ adnexal/adnexal.pdf.
37

Study Characteristics 

Types of data incorporated. Two of the studies54,56 included history or clinical impression 

as part of the “test;” results were not provided separately for examination alone. 

Types of study population. Ten of the 14 studies were performed prior to surgery for an 

adnexal mass, while four were from screening studies.51,52,57,58

Reporting of study populations. Of the screening studies, Andolf et al.52 was performed in 

women over 40 considered at high risk of ovarian cancer because of symptoms or risk factors; 

Grover and Quinn57 was performed in asymptomatic volunteers 25 and older, but described 

menopausal status; Adonakis et al.51 was performed in women over 45; and Jacobs et al.58 was 

done entirely in a postmenopausal population. 

Seven of the 11 preoperative studies reported menopausal status, but only two reported on 

test characteristics specifically by menopausal status.55,56 None reported race/ethnicity, and none 

reported the clinical route by which patients had come to surgery (detection of an asymptomatic 

mass, symptoms, etc.). 

Methodology. The methodological quality of the included studies was as follows: 

Reference standard. Of the preoperative studies, all but one42 had operative confirmation of 

findings. Ultrasound was used as the reference standard in the four screening studies, with 12-

month followup examinations or questionnaires. 

Verification bias. In the study by Roman et al.,42 26 women with non-palpable masses did 

not undergo definitive diagnosis. 

Test reliability. Only one study60 provided direct data on test reliability. Grover and 

Quinn,57 Ong et al.,59 Schutter et al.,63 and Buckshee et al.54 used a single examiner. The other 

studies did not address the issue of test reliability. 

Sample size. None of the reports had a priori sample size calculations. 

Use of appropriate statistical tests. All reports used appropriate techniques for calculating 

test characteristics. 

Blinding. Only two studies54,60 explicitly stated whether examiners were blinded to prior 

history or other findings. 

Definition of positive and negative test. Nine of 14 studies reported their definitions of a 

positive test, although the precision of the definitions was quite variable (from “a mass 5 cm or 

more in diameter” to “larger than normal”); others relied on “clinical impression.” 

 

 Results 

Table 7 and Figure 4 present the results of studies that evaluated the sensitivity of the 

bimanual examination for detecting an adnexal mass. The studies of Padilla et al.60,61 are 

particularly striking for the low sensitivity, since the examinations were performed under 

anesthesia, when, presumably, patient discomfort would not be a limiting factor. Both studies 

suggested a relationship between experience and accuracy; medical students performed worse 

than residents, who performed worse than attending physicians. Although these differences were 

not statistically significant, the studies were underpowered to detect significant differences. 

Obesity, defined as a body mass index greater than 30, had a significant negative impact on 

sensitivity, while increasing uterine size increased sensitivity, possibly by elevating the adnexae 

out of the pelvis. 
38

When sensitivity and specificity were combined separately using a random-effects model, the 

pooled sensitivity was 0.45 (95% confidence interval [CI], 0.28 to 0.68), and the pooled 

specificity was 0.90 (0.80 to 0.96). 

Table 7. Sensitivity and specificity of pelvic examination in detecting the presence of an adnexal mass 

Study N Sensitivity 

(95% CI) 

Specificity 

(95% CI) 

% with 

confirmed 

mass 

Notes 

Jacobs 

et al., 

198858

1,010 84.6% 

(65.0 to 100%) 

98.3% 

(97.5 to 99.1%) 

1.3% (0.1% 

malignant) 

Reference standard: ultrasound 

Screening study 

Andolf et 

al., 

199052

801 33.7% 

(26.5 to 41.0%) 

92.0% 

(89.9 to 94.1%) 

20% (0.1% 

malignant) 

Reference standard: ultrasound by 

midwife 

Screening in women considered at 

high risk for ovarian cancer; no ovarian 

cancers detected: 2 endometrial 

cancers, 1 LMP detected 

Padilla 

et al., 

200561

252 15.6% 

(8.1 to 23.0%) 

93.8% 

(90.1 to 97.5%) 

35.7% 

(unclear if 

any 

malignancies) 

Exam under anesthesia prior to 

surgery for pelvic mass; examiners 

blinded to radiology findings 

Likelihood of not detecting an adnexal 

mass increased with less experience 

(OR for resident 1.13, student 1.36 

compared to attending, although 95% 

CIs cross 1). 

Statistically significant increase in 

missed diagnosis if subject with BMI > 

30 (OR 2.57; 95% CI, 1.36 to 4.87), 

and significant decrease in presence 

of enlarged uterus (OR 0.48; 95% CI, 

0.25 to 0.93). 

Final diagnoses not presented, 

reasons for surgery not systematically 

presented 

Padilla 

et al., 

200060

140 

(82 

masses) 

Left adnexa 

(attending 

exam): 

32.7% 

(19.5 to 45.8%) 

Right adnexa 

(attending 

exam): 

21.2% 

(7.3 to 35.2%) 

Left adnexa 

(attending 

exam): 

88.5% 

(81.4 to 95.6%) 

Right adnexa 

(attending 

exam): 

78.7% 

(70.4 to 87.0%) 

58% (0 

malignancies) 

Exam under anesthesia prior to 

surgery for pelvic mass; examiners 

blinded to radiology findings; no clear 

relationship to experience 

Ong et 

al., 

199659

86 71.9% 

(60.9 to 82.9%) 

59.1% 

(38.5 to 78.6%) 

74.4% (0 

malignant) 

Pre-surgical exam 

Abbreviations: BMI = body mass index; CI = confidence interval; LMP = low malignant potential tumor; OR = odds 

ratio 
39

Figure 4. Performance of bimanual pelvic examination for detecting the presence of an adnexal mass 

Key to Figure 4: 1 = Jacobs et al., 1988;58 2 = Andolf et al., 1990;52 3 = Padilla et al., 2005;61 4 = Roman et al., 

1997;42 5 = Padilla et al., 2000;60 6 = Ong et al., 199659

Table 8 and Figure 5 show the test characteristics for discriminating benign from malignant 

masses. Using a random-effects model, pooled sensitivity was 0.72 (95% CI, 0.49 to 0.88) and 

specificity was 0.92 (0.80 to 0.97). When only the three screening studies were included, pooled 

sensitivity was 0.58 (95% CI, 0.21 to 0.88), pooled specificity 0.98 (0.97 to 0.98). 
40

Table 8. Sensitivity and specificity of pelvic examination in discriminating benign from malignant adnexal 

masses 

Study N Sensitivity 

(95% CI) 

Specificity 

(95% CI) 

% Malignant Notes 

Adonakis et 

al., 199651 2,000 66.7% 

(13.3 to 100%) 

97.2% 

(96.5 to 97.9%) 

0.15% Screening study; threshold 

of “abnormal or ambiguous 

exam;” CA-125 used in 

conjunction to proceed to 

ultrasound 

Grover et al., 

199557 2,623 0% 

(0 to 100%) 

98.5% 

(98.0 to 98.9%) 

0.05% Screening study; ultrasound 

and clinical followup 

Jacobs et al., 

198858 1,010 100% 

(0 to 100%) 

97.3% 

(96.3 to 98.3%) 

0.1% Screening study; followup 

with ultrasound 

Roman et al., 

199742 200 51.2% 

(36.3 to 66.1%) 

83.6% 

(77.8 to 89.4%) 

21% Results for 26 patients with 

non-palpable masses not 

included; no substantial 

difference based on 

menopausal status 

Buckshee et 

al., 199854 34 77.8 % 

(50.6 to 100%) 

88.9% 

(77.0 to 100%) 

25% One examiner; nonconsecutive patients prior 

to surgery 

Balbi et al., 

200153 72 90% 

(77.5 to 100%) 

74% 

(61.8 to 86.2%) 

31% 18 patients with “clearly 

benign masses” and 2 with 

“clearly malignant” 

excluded; clinical 

impression 

Finkler et al., 

198856 106 43.2% 

(27.3 to 59.2%) 

Premenopausal: 

16.7% 

(0 to 33.9%) 

Postmenopausal: 

68.4% 

(47.5 to 89.3%) 

90.8% 

(83.7 to 97.8%) 

Premenopausal: 

92.3% 

(85.1 to 99.6%) 

Postmenopausal: 

84.6% 

(65.0 to 100%) 

36% 

Premenopausal: 

26% 

Postmenopausal: 

59% 

“Clinical impression” 

included exam plus history; 

results not calculated for 

exam alone 

Schutter et al., 

199863 155 91.5% (84.4 to 

98.6%) 

73.9% (64.9 to 

82.9%) 

39% All postmenopausal; high 

prevalence of cancer; 

single examiner; 

inclusion/exclusion criteria 

not described 

Schutter et al., 

199462 222 92.6% 

(87.4 to 97.9%) 

63.0% 

(54.6 to 71.4%) 

43% Preoperative patients 

Dowd et al., 

199355 225 51.0% (41.7 to 

60.3%) 

Premenopausal: 

31% 

Postmenopausal 

59% 

87.0% (80.8 to 

93.2%) 

Premenopausal: 

95% 

Postmenopausal: 

75% 

49% Preoperative patients 

Abbreviations: CA-125 = cancer antigen 125; CI = confidence interval 
41

Figure 5. Performance of bimanual pelvic exam for distinguishing benign from malignant adnexal masses 

Key to Figure 5: 1 = Grover and Quinn, 1995;57 2 = Adonakis et al., 1996;51 3 = Jacobs et al., 1988;58 4 = Dowd et 

al., 1993;55 5 = Schutter et al., 1994;62 6 = Finkler et al., 1988;56 7 = Balbi et al., 2001;53 8 = Buckshee et al., 199854

For both types of studies, there appears to be a trend towards decreased specificity as 

prevalence increases, although the number of studies is small and the confidence intervals are 

wide. The extreme differences in sensitivity in the two largest studies (0 and 100 percent) 

prevent even a qualitative assessment of any relationship between prevalence and sensitivity. 

The two studies that stratified results by menopausal status55,56 found lower sensitivity and 

higher specificity for discriminating benign from malignant masses in premenopausal women 

compared to postmenopausal women (Table 8). 

Discussion 

Despite the common recommendation for routine pelvic examination, we found surprisingly 

little literature on its accuracy. Based on the literature we did identify, its sensitivity for 

detecting adnexal masses appears fairly low. Sensitivity for detecting normal adnexa is also low, 

as demonstrated in a recent study of examinations under anesthesia.64 Although sensitivity for 
42

distinguishing a malignant mass from a benign one is somewhat better, these results need to be 

interpreted with caution, since most of the studies were done in preoperative patients, who would 

already have a higher probability of having a malignancy. In the four large screening studies, 

there was a total of only five malignancies, with the bimanual detecting 0 percent, 66 percent, 

and 100 percent in the three individual studies where ovarian cancer was detected; the fourth had 

one case of a low malignant potential tumor and two endometrial cancers. Pooled sensitivity for 

the three screening studies that addressed discrimination between benign and malignant masses 

was considerably lower than for all studies combined (and was similar to the pooled sensitivity 

of the studies that examined the ability to detect any adnexal mass). 

Both types of studies show a trend toward decreased specificity as the prevalence of 

abnormality increases – this may reflect a greater degree of suspicion on the part of the 

examiner, based on other findings, and a greater likelihood of calling an examination abnormal. 

This is supported by the finding of the two studies which stratified results by menopausal status, 

which found higher sensitivity and lower specificity in postmenopausal women compared to 

premenopausal women.55,56 Because examiners were unblinded, and were likely aware of the 

higher prevalence of malignancy among postmenopausal women, they may have been more 

likely to assign a diagnosis of malignancy among those patients. Future studies need to pay 

stricter attention to blinding examiners to other information. In theory, this bias should also 

result in higher sensitivity as prevalence increases, although, because of the small number of 

studies, the small numbers of subjects in most studies, and the diametrically opposed findings of 

the two largest studies, we were unable to recognize any relationship. 

In the two studies that addressed the effect of experience on test characteristics,60,61 there 

appeared to be a relationship between increasing experience and increased sensitivity (specificity 

did not change); however, even attending physicians achieved a sensitivity of only 28 percent. 

Based upon the available literature, the bimanual examination does not appear to be a sensitive 

test for detecting the presence of adnexal masses and appears to have limited ability to 

discriminate benign from malignant masses. Although specificity was somewhat better, positive 

predictive values will still be quite low in low prevalence settings, as discussed under Question 

7. This will, in turn, lower the positive predictive value of diagnostic tests performed in patients 

referred on the basis of a pelvic examination. These tests are discussed in detail in the next 

section. 

Question 3: Single Modality Tests 

Question 3 is: Among women with a palpable adnexal mass on exam or a mass identified by 

ultrasound/imaging, what is the sensitivity/specificity of various evaluation modalities including 

ultrasound (transvaginal ultrasound [TVUS], transabdominal ultrasound, color Doppler, twodimensional [2D] versus three-dimensional [3D] ultrasound), computer tomography (CT) scan, 

magnetic resonance imaging (MRI) scan, and CA-125 levels for distinguishing benign from 

malignant masses? 

Approach 

This section considers the various evaluation modalities that are described in the literature 

and would be available to a clinician to aid in the work-up of an adnexal mass after it has been 
43

diagnosed. We focused our search on articles whose primary reference standard was 

histopathology. Ideally this reference standard would be applied to all test negatives. However, 

we accepted a repeat negative test (such as imaging) conducted at least 6 months later as an 

acceptable alternative. We did include some studies that were from population-based screening 

samples, and these will be considered in a separate section below. The evaluation modalities 

investigated can be divided into several general categories. Imaging studies will be divided by 

technological mode (ultrasound, MRI, etc.). Ultrasound studies will be divided into those that 

evaluate adnexal morphology (either by an explicit scoring system or by descriptive standards), 

those that measure vascular flow in the mass (Doppler), and those that evaluate these modalities 

in combination. Serum studies will focus primarily on CA-125, as this is the most common 

marker in both the literature and in clinical practice. However, other serum markers will be 

discussed as well. Finally, the studies for which it was possible to stratify by menopausal status 

will be discussed where appropriate. 

Results of Literature Search and Screening 

Two hundred and five articles were identified for abstraction. Of these, 153 met the 

inclusion criteria and were abstracted into Evidence Table 2 (Appendix D*

).31,33-36,39,42-44,46,47,49-

56,58,62,63,65-195

Ultrasound Morphology 

Conventional grey scale ultrasonography is the most common imaging modality used to 

differentiate benign from malignant adnexal masses. Especially with the advent of highfrequency transvaginal probes, the quality of the images allows description of the gross anatomic 

features of the lesion. This is, however, limited by the great variability of macroscopic 

characteristics of both benign and malignant masses. Furthermore, the technique is operator 

dependent. To overcome these limitations, morphologic scoring systems have been developed. 

Such scoring systems are based on specific ultrasound parameters each with several scores 

according to determined features and with a cutoff value to categorize masses as either malignant 

or benign. 

Table 9 describes the details of the most commonly used scoring systems. Briefly, the 

following scores are suggestive of malignancy: Sassone159 greater than 9, DePriest36 greater than 

or equal to 5, Ferrazzi93 greater than 9, and for Lerner131 greater than or equal to 3. Although the 

development of all the scoring systems was motivated to improve the reproducibility of 

morphological measurements, only the scoring system by Lerner et al. based the categories on a 

multivariate logistic analysis. 

 

* Appendixes cited in this report are provided electronically at 

http://www.ahrq.gov/downloads/pub/evidence/pdf/ adnexal/adnexal.pdf.
44

Table 9. Detailed description of ultrasound scoring systems 

Scoring 

system

Score 

Sassone et al., 

1991159 

Morphology 1 2 3 4 5 

Inner wall 

structure 

Smooth Irregularities ≤

3 mm 

Papillarities > 3 

mm 

Not applicable, 

mostly solid 

- 

Wall thickness 

(mm) 

Thin (≤ 3) Thick (> 3) Not applicable, 

mostly solid 

- - 

Septa (mm) None Thin (≤ 3) Thick (> 3) - 

Echogenicity Sonolucent Low 

echogenicity 

Low 

echogenicity 

with ochogenic 

core; mixed 

echogenicity 

- High 

echogenicity 

 

DePriest et al., 

199336 

Morphology 0 1 2 3 4 

Cystic wall 

structure 

Smooth (< 3 

mm thick) 

Smooth (> 3 

mm thick) 

Papillary 

projection (< 3 

mm) 

Papillary 

projection (≥ 3 

mm) 

Predominately 

solid 

Volume (cm3) < 10 10-50 > 50-200 > 200-500 > 500 

Septum 

structure 

No septa Thin septa (< 3 

mm) 

Thick septa (3 

mm to 1 cm) 

Solid area (≥ 1 

cm) 

Predominately 

solid 

 

Ferrazzi et al., 

199793 

Morphology 1 2 3 4 5 

Wall ≤ 3 mm > 3 mm - Irregular, 

mostly solid 

Irregular, not 

applicable 

Septa None ≤ 3 mm > 3 mm 

Vegetations None - - ≤ 3 mm > 3 mm 

Echogenicity Sonolucent Low 

echogenicity 

- With echogenic 

areas 

With 

heterogeneous 

echogenic 

areas, solid 

 

Lerner et al., 

1994131 

Morphology 0 1 2 3 

Wall structure Smooth or 

small 

irregularities < 

3 mm 

- Solid or not 

applicable 

Papillarities ≥ 

3 mm 

Shadowing Yes No - - 

Septa None or thin (< 

3 mm) 

Thick (≥ 3 mm) - - 

Echogenicity Sonolucent or 

low-level echo 

or echogenic 

core 

- - Mixed or high 

Reproducibility of tests. Timmerman et al.196 evaluated the subjective assessment of 

ultrasonographic images for discriminating between malignant and benign masses. Three 

hundred consecutive patients were evaluated with TVUS by six different operators, and both 
45

diagnostic accuracy and interassessor agreement were calculated. The operators had varied 

experience in TVUS – from approximately 300 to 15,000 scans. The two most experienced 

operators agreed 92 percent of the time. The accuracy of the least experienced operators ranged 

from 82 to 87 percent (p = 0.0001). Overall, 65 percent of all the masses were correctly 

classified by all six operators. Interassessor agreement was greater between the most 

experienced operators as well (kappa = 0.852). When comparing experienced with less 

experienced operators, the kappa ranged from 0.581 to 0.737. This is similar to the kappa 

reported by Yamashita et al.192 among five operators, 0.62 (± 0.02) with TVUS. Interassessor 

agreement was not calculated between the less experienced operators. None of the included 

articles described operator experience, and only a few addressed interobserver variability. 

Although operator experience appears to correlate with accuracy, the specialty training of the 

unltrasonographer does not. In a meta-analysis of both morphologic and color Doppler tests in 

the evaluation of adnexal masses, Kinkel et al.197 found no difference between radiologists and 

gynecologists in the performance of ultrasound. 

TVUS versus abdominal ultrasound. Of the 122 articles that evaluated adnexal masses via 

ultrasound (through either ultrasound morphology or Doppler measurements), only five articles 

exclusively used transabdominal imaging.52,58,116,133,198 Fifty-nine articles used TVUS 

exclusively and 51 used a combination of TVUS and abdominal ultrasound. There were seven 

articles for which the ultrasound modality was unknown. In the majority of the articles that used 

a combination of TVUS and abdominal ultrasound, TVUS was the “method of choice.” The 

most common reasons cited for also including abdominal ultrasound were patient refusal of 

transvaginal scans, virginity, poor image quality, and very large masses. Although a few articles 

reported how many women had which type of ultrasound, none of the articles reported their 

results such as to permit a stratification by TVUS or abdominal ultrasound. We therefore elected 

to group all ultrasound studies together regardless of TVUS or abdominal imaging. 

Trials identified. We identified 69 articles comprising 73 ultrasound morphology 

assessments. Despite the availability of published scoring systems, most of the studies based 

their diagnoses on either descriptive assessments of adnexal masses or used a modified or unique 

scoring system. Only 13 studies explicitly used Sassone’s criteria, six used DePriest’s, and three 

used Ferrazzi’s, Finkler’s, Lerner’s, and Valentin’s respectively. When a scoring system other 

than an established criterion was used, it was not always clear how it had been developed or 

modified. Details of the tests and their evaluative performance are provided in Table 10. 

Assessments of adnexal morphology by ultrasound which were either a unique or modified or 

unclear scoring system are labeled “other” with a brief description when possible. It is also 

important to note that not all of the established scoring systems were employed using the original 

cutpoints. For example, Caruso et al.83 and Itakure et al.115 both used a cutpoint of > 7 for the 

DePriest scoring system, where the original description used ≥ 5. 
46

Table 10. Sensitivity and specificity of ultrasound morphology 

Scoring system Pooled 

sensitivity 

(95% CI) 

Pooled 

specificity 

(95% CI) 

Range of 

sensitivity in 

individual 

studies 

Range of 

specificity in 

individual 

studies 

References 

Sassone 0.86 

(0.79 to 0.91) 

0.77 

 (0.73 to 0.81) 

0.65 to 1.00 0.65 to 0.93 43,54,68,69,83,93,130,131,1

54,159,160,163,179,193,199

 

DePriest 0.91 

(0.84 to 0.95) 

0.68 

(0.49 to 0.82) 

0.88 to 1.00 0.40 to 0.81 35,36,69,83,93,115

Ferrazzi 0.87 

(0.80 to 0.92) 

0.81 

(0.62 to 0.91) 

0.84 to 0.87 0.67 to 0.88 69,75,93

Finkler 0.82 

(0.65 to 0.91) 

0.78 

(0.59 to 0.91) 

0.52 to 0.88 0.55 to 0.70 56,62,63

Other (note: 

significant 

heterogeneity in 

criteria used for 

diagnosis – see 

ROC curve) 

0.86 

(0.82 to 0.89) 

0.83 

(0.76 to 0.88) 

0.43 to 1.00 0.29 to 1.00 33,34,39,42,43,67,69,74,76-

80,87,90,95,97,101,102,104,

106,108,112,117,118,122,12

4-127,133-135,138-

140,142,144,146,147,155,16

1,166,168,169,171,180,181,1

85,187,188,192,195

Abbreviations: CI = confidence interval; ROC = receiver operating characteristic

Results. The results of pooled sensitivity and specificity using a random-effects model, 

along with the range of sensitivity and specificity reported in individual studies, are shown in 

Table 10. Included studies are shown in Figures 6-10. There was a great range in test results, 

especially in the studies not using established scoring systems. This most likely reflects the 

heterogeneity of the tests themselves. There was little concrete difference among the established 

scoring systems. Overall the tests achieved relatively higher levels of sensitivity and negative 

predictive value (NPV) in the diagnosis of malignancy than specificity or positive predictive 

value (PPV). With the exception of four studies, the NPV was above 0.80, with the majority of 

tests above 0.90. The PPV in the majority of studies was below 0.50. In general, there was a 

trade-off between sensitivity and specificity, both in the individual studies of a specific scoring 

system, and in pooled results of all studies of a scoring system – as sensitivity increases, 

specificity decreases. 
47

Figure 6. Performance of ultrasound scoring according to Sassone’s criteria (1991) 

Key to Figure 6: 1 = Lerner et al., 1994;131 2 = Ferrazzi et al., 1997;93 3 = Sawicki et al., 2001;160 4 = Rehn et al., 

1996;154 5 = Sassone et al., 1991;159 6 = Caruso et al., 1996;83 7 = Leeners et al., 1996;130 8 = Alcazar and LopezGarcia, 2001;68 9 = Alcazar et al., 2003;69 10 = Timor-Tritsch et al., 1993;179 11 = Zanetta et al., 1994;193 12 = Alcazar 

et al., 1996;199 13 = Schneider et al., 1993;43 14 = Buckshee et al., 1998;54 15 = Sengoku et al., 1994163
48

Figure 7. Performance of ultrasound scoring according to DePriest’s criteria (1993) 

Key to Figure 7: 1 = Ferrazi et al., 1997;93 2 = Caruso et al., 1996;83 3 = DePriest et al., 1993;35 4 = Alcazar et al., 

2003;69 5 = Itakura et al., 2003;115 6 = DePriest et al., 199336
49

Figure 8. Performance of ultrasound scoring according to Ferrazzi’s criteria (1997) 

Key to Figure 8: 1 = Ferrazzi et al., 1997;93 2 = Berlanda et al., 2002;75 3 = Alcazar et al., 200369 
50

Figure 9. Performance of ultrasound scoring according to Finkler’s criteria (1988) 

Key to Figure 9: 1 = Schutter et al., 1994;62 2 = Schutter et al., 1998;63 3 = Finkler et al., 198856
51

Figure 10. Performance of ultrasound scoring according to various other unvalidated criteria 

Key to Figure 10: 1 = DePriest et al., 1997;34 2 = Marchetti et al., 2002;140 3 = Tailor et al., 2003;171 4 = Ekerhovd et 

al., 2001;90 5 = Canis et al., 1997;80 6 = Wakahara et al., 2001;187 7 = Maggino et al., 1994;135 8 = Schelling et al., 

2000;161 9 = Roman et al., 1997;42 10 = Brown et al., 1998;77 11 = Granberg et al., 1990;101 12 = Hermann et al., 

1987;108 13 = Kurjak and Predanic, 1992;125 14 = Tingulstad et al., 1996;180 15 = Stein et al., 1995;168 16 = Torres et 

al., 2002;181 17 = Manjunath et al., 2001;139 18 = Ma et al., 2003;134 19 = Valentin et al., 2001;185 20 = Franchi et al., 

1995;95 21 = Merce et al., 1998;146 22 = Davies et al., 1993;87 23 = Morgante et al., 1999;147 24 = Benjapibal et al., 

2003;74 25 = Gadducci et al., 1988;97 26 = Buy et al., 1996;79 27 = Strigini et al., 1996;169 28 = Luxman et al., 1991;133

29 = Kurjak et al., 1994;127 30 = Huber et al., 2002;112 21 = Reles et al., 1997;155 32 = Mancuso et al., 2004;138 33 = 

Kurjak et al., 2000;124 34 = Alcazar et al., 2003;69 35 = Kurjak et al., 1992;126 36 = Komatsu et al., 1996;122 37 = 

Yamashita et al., 1995;192 38 = Sohaib et al., 2005166 39 = Cohen et al., 2001;33 40 = Medl et al., 1995;144 41 = Hata 

et al., 1992;106 42 = Schneider et al., 1993;43 43 = Weiner et al., 1992;188 44 = Jain = 1994117 45 = Buist et al., 199478

46 = Alcazar et al., 200367 47 = Lin et al., 199339 48 = Jain et al., 1993;118 = Bromley et al., 1994;76 50 = Zimmer et 

al., 2003195

Comparing the figures, studies using the Sassone criteria show greater variability in 

sensitivity compared to variability in specificity (Figure 6), while those using the DePriest 

criteria (Figure 7) show greater variability in specificity and a relatively narrow range of 

sensitivity. Figure 10, which depicts a variety of other studies, suggests trade-offs between 

sensitivity and specificity; different morphology methods for discriminating benign from 

malignant have different thresholds, resulting in the sensitivity/specificity trade-off. 
52

Three articles compared different scoring systems within the same study population. Caruso 

et al.83 examined 112 women with adnexal masses comparing Sassone, DePriest, and Valentin 

scores. All performed similarly, displaying a sensitivity and NPV of 1.00, a range of specificity 

of 0.61 to 0.75, and a range of PPV of 0.35 to 0.48. Alcazar et al.69 also compared the 

performance of Sassone, DePriest, and Ferrazzi. There were no significant differences between 

these scoring systems when receiver operating characteristic (ROC) curves were compared. The 

area under the curve (AUC) was 0.89 for Sassone, 0.92 for DePriest, and 0.90 for Ferrazzi. 

Ferrazzi et al.93 evaluated 261 masses collected in three different centers. They compared ROC 

curves for scores based on Sassone, Granberg, DePriest, and Lerner’s criteria and compared it 

with a scoring system they developed. The AUC ranged from 0.72 to 0.75 for the previously 

established systems. Their new scoring system (Ferrazzi) performed better, with an AUC of 0.84 

(p < 0.0001). However, subsequent comparisons have not reaffirmed its superior functioning. 

When the Ferrazzi scoring system was compared to both Sassone and DePriest,69 its performance 

was almost identical. 

In spite of different designs, all the scoring systems performed similarly when compared 

within the same study population. It has been suggested that the poor performance of scoring 

systems with regard to their PPV is due to the misclassification of dermoid tumors.197 Dermoids 

share many of the features that are characterized as “malignant” in scoring systems. The Alcazar 

study proposes a scoring system that was developed in part to correct this. Although this scoring 

system does perform well in its initial application, it has not been independently verified. The 

authors conclude, “a completely reliable differentiation of malignant masses cannot be obtained 

by sonographic imaging alone.”69

Stratification by menopausal status. Of the 69 articles identified that addressed the 

assessment of adnexal morphology by ultrasound, only 13 contained data that either directly 

reported test characteristics by menopausal status or contained enough information to enable the 

stratification of results. Six were studies in a 100 percent postmenopausal patient population. 

Seven were studies that allowed comparison by menopausal status within the study population. 

They are presented in Table 11. The only significant difference in test performance appears to 

be in regards to the PPV. With the exception of Roman et al.,42 the PPV is slightly higher in 

postmenopausal women. This likely reflects the higher prevalence of ovarian malignancy after 

menopause. Aside from the PPV, the performance of ultrasound in the morphological 

assessment of adnexal masses does not appear to be significantly changed by menopausal status. 

Table 11. Ultrasound morphology assessment comparing pre- and postmenopausal status 

Study Scoring Premenopausal Postmenopausal 

System 

Sens Spec PPV NPV Sens Spec PPV NPV 

Finkler et al., 

198856 Finkler 0.50 0.96 0.50 0.77 0.78 0.92 0.94 0.75 

Franchi et al., 

199595 Descriptive 0.73 0.86 0.44 0.95 0.89 0.75 0.82 0.83 

Guerriero et al., 

2002105 Descriptive 0.98 0.89 0.44 1.00 1.00 0.51 0.52 1.00 

Reles et al., 

1997155 Modified score 1.00 0.79 0.46 1.00 0.87 0.89 0.77 0.94 

Roman et al., 

199742 Descriptive 0.93 0.92 0.66 0.99 0.81 0.62 0.54 0.86 

Schelling et al., 

2000161 Descriptive 0.91 0.84 0.29 0.99 1.00 0.73 0.62 1.00 
53

Study Scoring Premenopausal Postmenopausal 

System 

Sens Spec PPV NPV Sens Spec PPV NPV 

Alcazar et al., 

200369 Sassone 

DePriest 

Ferrazzi 

Alcazar 

1.00 

1.00 

1.00 

1.00 

0.88 

0.80 

0.84 

0.96 

0.50 

0.38 

0.43 

0.75 

1.00 

1.00 

1.00 

1.00 

0.61 

1.00 

0.82 

1.00 

0.88 

0.82 

0.82 

0.94 

0.81 

0.82 

0.79 

0.93 

0.73 

1.00 

0.85 

1.00 

Menon et al., 

2000145 Descriptive - - - - 1.00 0.94 0.24 1.00 

Schutter et al., 

199462 Finkler - - - - 0.88 0.64 0.65 0.88 

Bromley et al., 

199476 Unique scoring - - - - 0.91 0.52 0.52 0.92 

Schutter et al., 

199863 Finkler - - - - 0.86 0.70 0.65 0.89 

Luxman et al., 

1991133 Descriptive - - - - 0.93 0.55 0.45 0.95 

Kuriak et al., 

1992126 Unique scoring - - - - 0.48 0.98 0.93 0.78 

Abbreviations: NPV = negative predictive value; PPV = positive predictive value; Sens = sensitivity; Spec = 

specificity

Ultrasound Doppler Studies 

Color Doppler scanning allows the assessment of tumor vascularity. Malignant neoplasms 

have active blood vessel creation (angiogenesis) compared to normal or benign neoplasms due, 

in part, to their increased metabolic activity. Overall, malignancies display an increased 

vascularity with decreased peripheral blood flow resistance and increased blood flow velocity 

compared with benign tissue.152,200 Doppler signal analysis can separate high-resistance and 

low-resistance vessels and has therefore been investigated as a separate test modality, as well as 

in combination with ultrasound morphological evaluation in the evaluation of adnexal masses. 

The most common flow criteria are the resistance index (RI), the pulsatility index (PI), and 

the maximum systolic velocity. RI is defined as the difference between peak systolic and 

maximum enddiastolic flow velocity, divided by peak systolic flow velocity. Usually the lowest 

measured RI from a series of measurements is reported from different arteries. PI is defined as 

the difference between peak systolic and enddiastolic flow velocity, divided by the timeaveraged flow velocity. The maximum systolic velocity is the maximum flow recorded in any 

visualized artery. 

In order to make a measurement of either RI or PI or maximum systolic velocity, an artery 

must be identified on ultrasound. The inability to identify an artery in the mass means that the 

test cannot be performed. Therefore, not every individual included in the study population is 

captured with the assessment of these color Doppler modalities. Another limitation of these 

measurements is that the range observed in malignant masses overlaps with that observed in 

benign masses. For example, in Lin et al.,132 discussed in more detail below, the RI for 

malignant masses ranged from 0.23 to 0.82. Although they did not report a range for the benign 

masses, there were eight benign tumors with a RI < 0.4. This overlap limits the effectiveness of 

any threshold and, perhaps, contributes to the different thresholds reported in the literature. 

Reproducibility of tests. Timmerman et al.196 (discussed above under ultrasound 

morphology) included Doppler measurements in its analysis of interobserver variability and 

experience. In short, operators with more experience (300 versus 15,000 scans) had greater 
54

accuracy (92 percent versus 82 to 87 percent, p = 0.0001). Interassessor agreement was also 

greater between the most experienced operators (kappa = 0.852) compared with the less 

experienced operators (range 0.581 to 0.737). None of the articles evaluating color Doppler 

described operator experience, nor did any address interobserver variability specifically in 

regards to Doppler measurement. 

Trials identified. Fifty-six articles were identified that described color Doppler analysis, 

comprising a description of 65 tests. Thirty-two articles evaluated RI, 20 PI, and six the 

maximum systolic velocity. These are the most common flow criteria measured in the literature 

and presumably in clinical practice as well. Other Doppler parameters were described in the 

literature sometimes in conjunction with either RI or PI or maximum systolic velocity but were 

not included in this table. The other articles included 10 that involved the visualization of flow 

within the mass,70,71,104,105,119,137,160,161,168,182 two that involved counting the total number of 

arteries (either > 4152 or > 3199), and one that measured the absence of a diastolic notch.137

Results. Table 12 details the test characteristics of RI, PI, and the maximum systolic 

velocity in the evaluation of an adnexal mass, again using pooled values from a random-effects 

model. For RI the range reported was from ≤ 0.8 to < 0.4, with < 0.4 being the most common. 

For PI the range was relatively narrower from < 1.5 to < 1.0 with the majority of studies using 

either ≤ 1.0 or < 1.0. The reported range was greatest in the assessment of maximum systolic 

velocity, where there were also the fewest studies from > 30 cm/second to > 10 cm/second. As 

the threshold for RI decreases from ≤ 0.8 to < 0.4, the sensitivity and NPV decrease, and the 

specificity and PPV increase. This is seen most clearly in studies that evaluated a series of RI 

cutpoints with the same study population.132,176

Lin et al.132 evaluated 370 women with adnexal masses who were scheduled for surgery at a 

single institution. They reported outcomes based on RI cutpoints of 0.4, 0.5, and 0.6. For RI < 

0.4, the sensitivity, specificity, PPV, and NPV were 0.69, 0.97, 0.89, and 0.91, respectively. For 

RI < 0.5, they were 0.79, 0.92, 0.77, and 0.93. And for < 0.6, they were 0.91, 0.86, 0.68, and 

0.98. The authors conclude that the 0.4 cutpoint yields the highest concordance rate between 

Doppler prediction and histopathologic diagnosis. This conclusion, however, is based more on 

clinical impression, as ROC curve analysis was not performed. 

The range of Doppler study performance is listed in Table 12 and shown in Figures 11-13. 

Overall there was great heterogeneity of performance results. The range of sensitivity was 

largest for RI. This range did not appear to be secondary to differences in RI thresholds; 

however, the < 0.4 threshold did appear to narrow specificity results. In spite of the large 

variation in thresholds described for maximum systolic velocity, the range of test characteristics 

was somewhat narrower than that for RI, probably because there were fewer studies identified 

that used this measurement. Again, there is a trade-off between sensitivity and specificity, 

although this appears greatest for maximum velocity. 
55

Table 12. Sensitivity and specificity of Doppler studies 

Doppler method Pooled 

sensitivity 

(95% CI) 

Pooled 

specificity 

(95% CI) 

Range of 

sensitivity 

in 

individual 

studies 

Range of 

specificity 

in 

individual 

studies 

References 

Resistance index 0.76 (0.68 

to 0.73) 

0.89 

(0.84 to 

0.92) 

0.19 to 1.00 0.53 to 1.00 43,68,70,75,76,79,81,86,88,95,106,107,1

17,124-

126,128,130,132,141,146,152,168,172,1

75,176,179,184,190,193,199,201

Pulsatility index 0.79 

(0.73 to 

0.83) 

0.74 

(0.64 to 

0.81) 

0.57 to 0.95 0.32 to 0.97 73,79,81,94,103,109,115,120,154,155,15

8,163,168,169,179,182,184,188,199,201

Maximum systolic 

velocity 

0.76 

(0.61 to 

0.86) 

0.83 

(0.66 to 

0.93) 

0.48 to 0.94 0.43 to 0.97 68,79,107,109,152,199
56

Figure 11. Performance of Doppler ultrasound resistance index 

Key to Figure 11: 1 = Kurjak et al., 1991;128 2 = Wu et al., 1994;190 3 = Lin et al., 1993;132 4 = DePriest et al., 1994;88

5 = Prompeler et al., 1996;152 6 = Tepper et al., 1995;176 7 = Kurjak and Predanic, 1992;125 8 = Valentin, 2000;184 9 = 

Stein et al., 1995;168 10 = Anandakumar et al., 1996;70 11 = Valentin, 1996201 12 = Franchi et al., 1995;95 13 = Merce 

et al., 1998;146 14 = Carter et al., 1995;81 15 = Takac, 1998;172 16 = Buy et al., 1996;79 17 = Leeners et al., 1996;130 18 

= Chou et al., 1994;86 19 = Hata et al., 1995;107 20 = Marret et al., 2004;141 21 = Kurjak et al., 2000;124 22 = Kurjak et 

al., 1992;126 23 = Timor-Tritsch et al., 1993;179 24 = Zanetta et al., 1994;193 25 = Tekay and Jouppila, 1992;175 26 = 

Alcazar et al., 1996;199 27 = Hata et al., 1992;106 28 = Schneider et al., 1993;43 29 = Berland et al., 2002;75 30 = 

Alcazar and Lopez-Garcia, 2001;68 31 = Jain, 1994;117 32 = Bromley et al., 199476
57

Figure 12. Performance of Doppler ultrasound pulsatility index 

Key to Figure 12: 1 = Rehn et al., 1996;154 2 = Guerriero et al., 1998;103 3 = Valentin, 2000;184 4 = Stein et al., 

1995;168 5 = Itakure et al., 2003;115 6 = Valentin, 1999;201 7 = Valentin, 1997182 8 = Carter et al., 199581 9 = Buy et al., 

1996;79 10 = Benjapibal et al., 2002;73 11 = Kawai et al., 1994;120 12 = Strigini et al., 1996;169 13 = Hillaby et al., 

2004;109 14 = Salem et al., 1994;158 15 = Timor-Tritsch et al., 1993;179 16 = Reles et al., 1997;155 17 = Alcazar et al., 

1996;199 18 = Fleischer et al., 1992;94 19 = Weiner et al., 1992;188 20 = Sengoku et al., 1994163
58

Figure 13. Performance of Doppler ultrasound velocity indices 

Key to Figure 13: 1 = Prompeler et al., 1996;152 2 = Buy et al., 1996;79 3 = Hillaby et al., 2004;109 4 = Alcazar et al., 

1996;199 5 = Alcazar and Lopez-Garcia, 200168

Table 13 compares the characteristics of Doppler studies that did not use measurement or 

calculation of Doppler waveforms. They relied instead on either the presence of vascularity 

within the mass (yes/no) or on a direct count of vessels seen. These tests seem to perform as 

well as the RI or PI in terms of sensitivity, although specificity varies quite widely (Figure 13). 

Valentin182 measured both the PI (< 1.0) and the presence of color lakes visible on Doppler in the 

same study population. Of 151 patients, PI was measured in 135, indicating that for 16 

individuals, no artery was visualized within the mass. The sensitivity reported for the PI was 

0.83, specificity 0.34, PPV 0.20, and NPV 0.91. Simply documenting the presence or absence of 

visible color lakes on Doppler yielded a sensitivity of 0.88, a specificity of 0.67, a PPV of 0.33, 

and a NPV of 0.97. Not only did the direct visualization test perform better, but because its 

outcome was a simple binary outcome (present or absent), the results included the entire study 

population (n = 151). Prompeler et al.152 measured RI, maximum systolic velocity, as well as the 

number of arteries visualized in the mass. Their data for the simple counting of arteries also 

performs as well if not better than the calculated tests such as RI or PI. In a random-effects 
59

model, pooled sensitivity for the presence or absence of blood flow within a mass was 0.88 (95% 

CI, 0.80 to 0.92) and pooled specificity 0.78 (95% CI, 0.65 to 0.87) 

Table 13. Study characteristics of simple Doppler visualization 

Study 

(N) 

Test Sensitivity Specificity 

Prompeler et al., 1996152 

(212) 

Total number of arteries > 4 

(postmenopausal women only) 

0.82 0.92 

Valentin, 1997182 

(151) 

Color lakes visible on Doppler 0.88 0.67 

Maly et al., 1995137 

(102) 

Demonstrable blood vessels 0.95 0.30 

Schelling et al., 2000161 

(257) 

Central vascularity on Doppler in solid 

component 

0.93 0.94 

Stein et al., 1995168 

(170 masses) 

Internal flow within solid component or 

septation 

0.77 0.69 

Guerriero et al., 2002105 

(826 masses) 

Arterial flow visualized in an echogenic 

structure or irregular solid portion 

0.95 0.92 

Anandakumar et al., 199670

(146) 

“Continuously fluctuating” vessels with 

turbulent flow 

0.77 0.68 

Antonic and Rakar, 199571

(71) 

Color flow present 0.89 0.47 

Guerriero et al., 2005104

(424) 

Color flow present in “echogenic structure” 1.00 0.91 

Juhasz et al., 1990119

(147) 

Color flow present in mass 0.96 0.84 
60

Figure 14. Performance of Doppler ultrasound for intratumoral blood flow 

Key to Figure 14: 1 = Guerriero et al., 2005;104 2 = Schelling et al., 2000;161 3 = Prompeler et al., 1996;152 4 = Stein et 

al., 1995;168 5 = Valentin, 1997;182 6 = Maly et al., 1995;137 7 = Anandakumar et al., 1996;70 8 = Antonic and Rakar, 

199571

Stratification by menopausal status. Out of a total of 56 studies identified that evaluated 

color Doppler, only 11 contained data that either directly reported test characteristics by 

menopausal status or contained enough information to enable the stratification of results. Two of 

these studies were in a 100 percent postmenopausal population, and nine enabled comparison by 

menopausal status within the same study population (Table 14). When comparing test 

performance within the same study population stratified by menopausal status, the PPV of the 

test is significantly increased in the postmenopausal group. In Salem et al.,158 the PPV increased 

only from 0.20 in the premenopausal group to only 0.47 in the peri- and postmenopausal group. 

This may be a reflection of how they defined peri- and postmenopause (which was not clearly 

stated by the authors). After stratifying the reported results by age (> 45), the PPV is 0.73. This 

increase in PPV among postmenopausal women appears to be greater in the context of Doppler 

studies than that observed with ultrasound morphology. This finding differs from the one metaanalysis on the subject. Kinkel et al.197 did a systematic review of both ultrasound morphology 

and Doppler in the detection of malignant masses. Although they noted a difference in outcomes 
61

dependent on menopausal status, this difference did not reach statistical significance. 

Interestingly, there was a difference in terms of Doppler test performance by year of publication 

with better results demonstrated by earlier studies (p = 0.005), a result that was independent of 

sample size. 

Table 14. Doppler studies stratified by menopausal status 

Study Premenopausal Postmenopausal 

(N) 

Test 

Sens Spec PPV NPV Sens Spec PPV NPV 

Franchi et al., 

199595

(129) 

RI < 0.65 0.82 0.72 0.31 0.96 0.86 0.75 0.82 0.83 

Guerriero et al., 

2002105

(826 masses) 

Arterial flow visualized in 

echogenic structure or 

irregular solid portion 

0.94 0.96 0.67 1.00 0.96 0.77 0.69 0.97 

Reles et al., 

1997155

(98) 

PI ≤ 1.1 0.80 0.67 0.36 0.93 0.93 0.83 0.76 0.91 

Schelling et al., 

2000161

(257) 

Presence of central 

vascularization on Doppler 

0.91 0.94 0.53 0.99 0.93 0.92 0.84 0.97 

Prompeler et 

al., 1996152

(212) 

Total number of arteries > 

4 

RI > 0.5 

Maximum systolic velocity 

> 30cm/s 

0.85 

0.84 

0.92 

0.71 

0.47 

0.65 

0.36 

0.23 

0.33 

0.96 

0.94 

0.98 

0.82 

0.82 

0.76 

0.82 

0.69 

0.88 

0.76 

0.66 

0.82 

0.86 

0.84 

0.84 

Strigini et al., 

1996169

(109) 

PI < 1 0.83 0.73 0.21 0.98 0.85 0.81 0.73 0.90 

Salem et al., 

1994158

(109 masses) 

PI < 1 1.00 0.84 0.20 1.00 0.73 0.71 0.47 0.88 

Szpurek et al., 

2004170

(464) 

Doppler subjective index ≥

4 

0.82 0.93 0.79 0.94 0.92 1.00 1.00 0.82 

Kurjak et al., 

1992126

(83) 

RI < 0.41 

randomly separate vessels 

- 

- 

- 

- 

- 

- 

- 

- 

0.96 

0.90 

0.95 

0.98 

0.90 

0.96 

0.98 

0.95 

Bromley et al., 

199476

(33) 

RI < 0.6 - - - - 0.66 0.81 0.67 0.81 

Antonic and 

Rakar, 199571

(71) 

Presence of color flow 1.00 0.36 0.11 1.00 0.87 0.79 0.81 0.85 

Guerriero et al., 

1998103

(192 masses) 

PI ≤ 1 0.86 0.46 0.08 0.98 0.88 0.52 0.66 0.81 

Abbreviations: NPV = negative predictive value; PI = pulsatility index; PPV = positive predictive value; RI = 

resistance index; Sens = sensitivity; Spec = specificity

Combined Ultrasound Morphology and Doppler 

A limiting feature of ultrasound morphologic assessments has been felt to be the high rate of 

false positive test results.196 Color Doppler, in contrast, has displayed a slightly higher PPV, 

especially in the earlier studies.197 There have, therefore, been attempts to combine ultrasound 

morphology and Doppler studies in a single test. 
62

Trials identified. Of all the articles that investigated the use of either ultrasound 

morphology or color Doppler in the evaluation of an adnexal mass, nine articles containing a 

total of 13 tests described a combination ultrasound morphology and Doppler 

modality.65,79,91,100,123-125,130,201 

Results. There is a large range in the reported study performance (sensitivity ranges from 

0.71 to 0.98, specificity from 0.6 to 1.0. The relevant studies are shown in Figure 15; all but two 

had both sensitivity and specificity above 0.80. Pooled sensitivity in a random-effects model 

was 0.89 (95% CI, 0.81 to 0.93) and pooled specificity 0.91 (0.80 to 0.96). Both of these values 

were higher than the pooled values for any morphology or Doppler method alone. 

Figure 15. Performance of combined ultrasound morphology and color Doppler 

Key to Figure 15: 1 =Kurjak and Predanic, 1992;125 2 =Valentin, 1999;201 3 =Kurjak and Kupesic, 1999;123 4 =Buy et 

al., 1996;79 5 =Leeners et al., 1996;130 6 =Grab et al., 2000;100 7 =Fenchel et al., 2002;91 8 =Kurjak et al., 2000;124 9 = 

Alcazar and Castillo, 200565

Stratification by menopausal status. There were two studies that analyzed combined 

ultrasound morphology and Doppler in 100 percent post menopausal patient populations. Kurjak 

et al.126 reported a combined sensitivity, specificity, PPV, and NPV of 0.90, 0.94, 0.90, and 0.94, 

respectively. Their combined test consisted of RI < 0.41 and an ultrasound morphology scoring 
63

system unique to them. Veunto et al.186 in a population-based screening study reported a 

sensitivity, specificity, PPV, and NPV of 1.00, 0.83, 0.006, and 1.00, respectively. Given that 

these two studies are of greatly different design, it is hard to compare them directly. Comparing 

Kurjak et al. to the range of combined ultrasound and Dopper studies, it appears that in the 

postmenopausal group, the test has a better performance. However, this test performance may 

reflect patient selection criteria for the study that was not clearly explained. Combination 

modalities as a screening tool for ovarian cancer had a high false positive rate (as seen in the 

PPV of 0.006186). 

3D Versus 2D Ultrasound 

We identified five studies that analyzed 3D ultrasound. Four are listed in Table 15. The 

fifth, by Cohen et al.,33 was not included because it compared 2D ultrasound with 2D plus some 

component of a 3D exam (possibly 3D Doppler) that was not clearly stated in the article. 

Overall, 3D ultrasound appears superior to 2D especially in regards to sensitivity and PPV 

performance. We were unable to stratify these results by menopausal status. Test reliability and 

variability were not addressed specifically in terms of 3D ultrasound. 

Table 15. 3D versus 2D ultrasound 

Study 

(number of 

persons) 

Test Sensitivity Specificity PPV NPV 

Alcazar et al., 

200367

(41 masses) 

2D 

3D 

Presence of one of the following fulfilled 

criteria for mass: > 3 mm wall, > 3 mm 

septum, > 3 mm papillary projections, solid 

areas or echogenicity 

0.90 

1.00 

0.61 

0.78 

0.68 

0.81 

0.88 

1.00 

Kurjak and 

Kupesic, 1999123

(120) 

2D 

3D 

Both used a unique scoring system that 

included Doppler measurements 

0.91 

1.00 

0.97 

0.99 

0.77 

0.92 

0.99 

1.00 

Kurjak et al., 

2000124

(90) 

2D morphology 

2D Doppler 

2D combined 

3D morphology 

3D Doppler 

3D combined 

Both used a unique scoring system for 

morphological assessment. Doppler for 2D 

was RI ≤ 0.42, for 3D it was “complex” 

“chaotic” vessel arrangement 

0.67 

0.89 

0.89 

0.78 

0.89 

1.00 

0.94 

0.95 

0.98 

0.98 

0.98 

0.99 

0.55 

0.67 

0.80 

0.78 

0.80 

0.90 

0.96 

0.99 

0.99 

0.98 

0.99 

1.00 

Alcazar and 

Castillo, 200565

(69 masses) 

2D 

3D 

Presence of at least one of the following 

fulfilled criteria for “complex mass”: >3mm 

wall, > 3 mm papillary projection, solid areas 

or purely solid echogenicity 

Doppler flow in mass also used in test but 

unclear how 

0.98 

0.98 

0.88 

0.79 

0.94 

0.90 

0.96 

0.95 

Abbreviations: 2D = two-dimensional; 3D = three-dimensional; NPV = negative predictive value; PPV = positive 

predictive value
64

Other Imaging Modalities 

Although ultrasound remains the most common imaging modality in the evaluation and 

diagnosis of adnexal masses, newer technologies such as MRI, CT, and positron emission 

tomography (PET) have been studied as well. These modalities may not be as readily available 

to the clinician as ultrasound, and there is less literature devoted to them than to ultrasound; 

however, they are included in this review because of growing interest both clinical and research 

in their use. Further, despite refinements in ultrasound morphology scoring systems or Doppler 

measurements, the overall performance of ultrasound in the evaluation of the adnexal mass may 

be relatively fixed by the technology itself. Therefore it is necessary to investigate other imaging 

modalities and see how they compare with ultrasound. 

Reproducibility of tests. Unlike ultrasound, MRI, CT, and PET images are not operator 

dependent in terms of obtaining the images. There is, however, the potential for interobserver 

variability in their analysis. There are no standardized morphological scoring systems for any 

imaging modality other than ultrasound. We identified two articles that directly addressed the 

issue of test reproducibility for either MRI and/or CT in the evaluation of adnexal masses. Buist 

et al.,78 however, reported a series of 64 women who were evaluated by both MRI and CT and 

reviewed by two different radiologists. They reported a kappa value for the interobserver 

reliability for distinguishing between benign and malignant disease of 0.28 for CT and 0.41 for 

MRI. Yamashita et al.192 also calculated kappa values for interobserver variability among five 

radiologists. They showed far greater agreement: for precontrast MRI, kappa = 0.71 (± 0.02); 

for contrast-enhanced MRI, kappa = 0.73 (± 0.02). 

Trials identified. We identified 17 articles comprising 22 tests. There were 15 articles for 

MRI, three for CT, and three for PET and one that used a combined CT/MRI test. There were 

two articles that investigated nuclear medicine technologies in the evaluation of adnexal masses. 

These, however, were not included in the review given the experimental nature of such tests at 

this time. The PET studies were all performed also using tracer 18-Fluorodeoxyglucose (FDG) 

with the test measuring uptake of FDG in the lesion. 

Results. The results of MRI, CT, and PET modalities are summarized in Table 16. All of 

the articles describing CT and PET and most of the articles describing MRI either used 

descriptive criteria for differentiating malignant from benign appearing lesions or did not report 

the criteria used. Only two articles for MRI used a scoring system, slightly different from each 

other, which increases the difficulty in comparing studies. To date, there are no standardized 

scoring systems for any imaging modality other than ultrasound. 

The range of test performance of MRI, CT, and PET are shown in Table 16. Table 17 

includes, for comparison, the test performance for ultrasound morphology, color Doppler (all the 

modalities), and ultrasound morphology and Doppler combined. Tian et al.177 was excluded 

from this table because there was no description how CT and MRI were combined for a single 

test result (in series versus in parallel). Overall the sensitivity for MRI, CT, and PET are similar 

to that of combined ultrasound morphology and Doppler and less heterogenous than either 

modality separate. The specificity, however, is equivalent to either test separate and wider than 

the tests combined, with the exception of FDG-PET. However, the comparatively narrow range 

of both CT and PET results could be secondary to the relatively few studies that use these 

modalities. There is a large range of results for PET PPVs and a small range for CT, again 

possibly reflecting the paucity of studies. The range of NPVs for MRI is comparable to that for 

combined ultrasound morphology and Doppler and better than either CT or PET. Overall MRI 
65

appears similar in performance to combined ultrasound. More research is needed to accurately 

assess the performance range of CT and PET. 

Table 16. Sensitivity and specificity of other imaging modalities 

Imaging 

modality 

Pooled 

sensitivity 

(95% CI) 

Pooled 

specificity 

(95% CI) 

Range of 

sensitivity in 

individual 

studies 

Range of 

specificity in 

individual 

studies 

References 

MRI 0.91 (0.86 to 

0.94) 

0.87 (0.83 to 

0.90) 

0.67 to 1.00 0.77 to 1.00 44,78,91,100,106,111,112,118,121,122

,129,144,156,166,192

CT 0.90 

(0.83 to 0.94) 

0.75 

(0.36 to 0.94) 

0.86 to 0.96 0.35 to 0.89 39,78,129

FDG-PET 0.67 

(0.52 to 0.79) 

0.79 

(0.70 to 0.85) 

0.58 to 0.78 0.76 to 1.00 91,100,121

Abbreviations: CI = confidence interval; CT = computed tomography; FDG = 18-Fluorodeoxyglucose; MRI = 

magnetic resonance imaging; PET = positron emission tomography

Another way to compare imaging modalities is by looking at studies that compare imaging 

modalities within the same study population. These are listed in Table 17. There may be a small 

benefit in performance of MRI over ultrasound, especially in terms of PPV. There is no 

evidence to support the superiority of any single modality, although FDG-PET appears inferior 

to the rest. 

Table 17. Comparison of MRI, CT, FDG-PET, and ultrasound 

Study 

(N) 

Test Sensitivity Specificity PPV NPV 

Medl et al., 

1995144

(73) 

Ultrasound morphology (descriptive) 

MRI descriptive 

0.81 

0.97 

0.73 

0.83 

0.79 

0.88 

0.76 

0.96 

Yamashita et al., 

1995192

(72 women 80 

masses) 

Ultrasound morphology (unique score) 

MRI precontrast 

MRI contrast enhanced 

0.89 

0.78 

0.91 

0.84 

0.93 

0.93 

0.63 

0.79 

0.81 

0.96 

0.93 

0.97 

Fenchel et al., 

200291

(99) 

Ultrasound combined morphology and 

Doppler 

MRI 

FDG-PET 

0.92 

0.83 

0.58 

0.60 

0.83 

0.76 

0.24 

0.40 

0.25 

0.98 

0.97 

0.93 

Jain et al., 

1993118

(32) 

Ultrasound morphology (descriptive) 

MRI 

1.00 

0.67 

0.60 

1.00 

0.18 

1.00 

1.00 

0.97 

Kawahara et al., 

2004121

(38) 

MRI descriptive 

FDG-PET 

0.91 

0.78 

0.87 

1.00 

0.91 

1.00 

0.87 

0.75 

Komatsu et al., 

1996122

(82) 

Ultrasound morphology (unique score) 

MRI descriptive (n = 59) 

1.00 

0.91 

0.46 

0.88 

0.57 

0.91 

1.00 

0.88 

Lin et al., 199339

(80) 

Ultrasound morphology (descriptive) 

CT descriptive 

0.83 

0.86 

0.50 

0.36 

0.58 

0.74 

0.79 

0.56 

Buist et al., 

199478

(64) 

CT reviewer a 

CT reviewer b 

MRI reviewer a 

MRI reviewer b 

Ultrasound morphology (NR) 

0.96 

0.89 

0.96 

0.96 

0.89 

0.44 

0.83 

0.33 

0.94 

0.44 

0.72 

0.89 

0.68 

0.96 

0.71 

0.89 

0.83 

0.86 

0.94 

0.73 

Grab et al., 

2000100 Ultrasound combination morphology 

and Doppler 

0.92 

0.83 

0.60 

0.84 

0.23 

0.42 

0.98 

0.97 
66

Study 

(N) 

Test Sensitivity Specificity PPV NPV 

(101) MRI descriptive 

FDG-PET 

0.58 0.80 0.28 0.93 

Hata et al., 

1992106

(63) 

Ultrasound (NR) 

MRI score 

0.85 

0.67 

0.69 

0.97 

0.68 

0.95 

0.86 

0.80 

Huber et al., 

2002112

(93) 

Ultrasound morphology (descriptive) 

MRI descriptive 

0.85 

0.89 

0.73 

0.86 

0.87 

0.93 

0.71 

0.79 

Reuter et al., 

1998156

(65) 

Ultrasound morphology (descriptive) 

MRI descriptive 

1.00 

1.00 

0.66 

0.78 

0.40 

0.50 

1.00 

1.00 

Sohaib et al., 

2005166

(72) 

Ultrasound morphology (descriptive) 

MRI descriptive 

1.00 

0.97 

0.40 

0.84 

0.53 

0.80 

1.00 

0.97 

Abbreviations: CT = computed tomography; FDG = 18-Fluorodeoxyglucose; MRI = magnetic resonance imaging; NR 

= not reported; PET = positron emission tomography

Only two studies compared pre- and postcontrast enhancement with MRI.111,192 Contrast 

enhancement improved evaluative performance in both studies, particularly sensitivity. In 

Hricak et al. the sensitivity increased from 0.87 to 0.95, specificity from 0.75 to 0.79, PPV from 

0.78 to 0.83, and NPV 0.84 to 0.94.111 These results are similar to those of Yamashita et al.192 in 

Table 17. 

Stratification by menopausal status. None of the studies describing MRI, CT, or PET 

reported results either by menopausal status or in data that would allow menopausal status to be 

stratified. 

Serum Markers: CA-125 

The concept of using tumor markers as either screening or diagnostic tests for ovarian cancer 

is dependent upon identifying an abnormal level of a particular marker in serum, reflecting a 

systemic effect of disease in the ovary. The most extensively investigated ovarian cancer 

associated antigen is CA-125. This antigen is recognized by a murine monoclonal antibody 

produced using an ovarian cancer cell line as an immunogen. Elevated levels are detected in 

approximately 80 percent of ovarian carcinomas at the time of diagnosis;136,167 however, elevated 

serum levels have also been reported in a variety of benign conditions, potentially affecting 

specificity. In addition, CA-125 is not as commonly elevated in non-epithelial ovarian cancers. 

Because these stromal and germ cell tumors are proportionately more common in premenopausal women, the sensitivity of CA-125 may it is not as sensitive in premenopausal 

women.3

 

Reproducibility of tests. Only one study included specific information regarding the interand intra-assay coefficients of variation.66 They were < 7.5 percent and < 5.3 percent, 

respectively. The sensitivity of the assay in this study was < 5 U/ml. 

Trials identified. We identified 66 studies that investigated the use of CA-125 as a serum 

marker in the evaluation of an adnexal mass. One study was a population-based screening study 

that employed CA-125 as part of the screening triage.51 Forty-six studies in total used 35 U/ml 

as a threshold – in 37 it was the only threshold used, whereas in five, both 35 U/ml and another 

threshold were reported for the same patient population. There were 24 studies that reported a 

threshold other than 35 U/ml ranging from >20 U/ml to >100 U/ml. In addition to the five 
67

studies that reported 35 U/ml and an additional level, there were four other studies that reported 

two threshold levels within the same study population. All but one of the studies were case 

series. Although there were a few studies that compared CA-125 results from operative cases 

with normal controls, only the data from the operative series were included in the 2-by-2 tables. 

The clinical presentation of the cases was rarely described. Some of the series were drawn from 

oncology clinics 

Results. At the most commonly used threshold of 35 U/mL, the pooled sensitivity of CA125 for discriminating benign from malignant lesions was 0.78 (95% CI, 0.75 to 0.81), and the 

pooled specificity 0.78 (95% CI, 0.71 to 0.82). Individual study sensitivities ranged from 0.45 to 

1.0, and specificities from 0.46 to 0.99; see Figure 16, where the trade-off between sensitivity 

and specificity resulting from different thresholds is clearly seen. Not including the one 

screening study in this series,51 the studies ranged in size from 52 to 429 individuals. Unlike 

ultrasound morphology assessments, the range of CA-125 performance is not influenced by the 

heterogeneity of evaluative modalities. However, the results of performance have, overall, a 

similarly broad range. This most likely reflects heterogeneity of study populations. As very few 

studies actually reported how patients were diagnosed with masses, it is impossible to accurately 

stratify these results by patient characteristics. As with ultrasound measurements (both 

morphology and Doppler), the narrowest range of CA-125 test performance was with NPV, 

making this, perhaps, the most reliable part of the test itself. 
68

Figure 16. Performance of CA-125 

Key to Figure 16: 1 = Adonakis et al., 1996;51 2 = Woolas et al., 1995;189 3 = Gadducci et al., 1992;98 4 = Wakahara 

et al., 2001;187 5 = Maggino et al., 1994;135 6 = Dowd et al., 1993;55 7 = Schutter et al., 2002;162 8 = Patsner and 

Mann, 1988;151 9 = Roman et al., 1997;42 10 = Schutter et al., 1994;62 11 = Gadducci et al., 1991;99 12 = Chen et al., 

1988;85 13 = Vasilev et al., 1988;50 14 = Timmerman et al., 1999;178 15 = Hogdall et al., 2000;110 16 = Malkasian et 

al., 1988;136 17 = Torres et al., 2002;181 18 = Schutter et al., 1998;63 19 = Manjunath et al., 2001;139 20 = Troiano et 

al., 1997;47 21 = Chalas et al., 1992;31 22 = Mancuso et al., 2004;138 23 = Gadducci et al., 1988;97 24 = Finkler et al., 

1988;56 25 = Tay and Chua, 1994;174 26 = Soper et al., 1990;167 27 = Smikle et al., 1995;46 28 = Hurteau et al., 

1995;113 29 = Asif et al., 2004;72 30 = Einhorn et al., 1986;89 31 = Hillaby et al., 2004;109 32 = Alcazar et al., 1999;66 33 

= Balbi et al., 2001;53 34 = Antoni and Rakar, 1995;71 35 = Hata et al., 1992;106 36 = O’Connell et al., 1987;148 37 = 

Schneider et al., 1993;43 38 = Weiner et al., 1992;188 39 = Tian et al., 2000;177 40 = Berlanda et al., 2002;75 41 = 

Sengoku et al., 1994163

The only screening study identified for CA-125 in our literature search51 included 2000 

women. The sensitivity in this study was 1.00, specificity 0.99, PPV 0.17, and NPV 1.00. Few 

of the other studies achieved this degree of sensitivity, specificity, or NPV, although overall the 

PPV was higher. In the presence of an adnexal mass, the false negative rate increases compared 

with a screened population reflecting the fact that benign gynecologic disease can cause 

elevation of CA-125. 

The most common threshold other than 35 U/ml was 65 U/ml. Most of the studies using 65 

U/ml as a threshold were from Asia. The probable heterogeneity of study populations makes 
69

comparisons between these levels limited. Looking at the studies that reported results for 

different levels of CA-125 for within the same study population,87,98,134,136,147,148,162,167,180 in the 

higher threshold measurement, the specificity and PPV are higher, the sensitivity is lower, and 

the NPV is only slightly lower. 

Stratification by menopausal status. Of the 59 studies we identified that examined CA125, only nine contained data that either directly reported test characteristic by menopausal status 

or contained enough information to enable the stratification of results. One study was conducted 

exclusively in a postmenopausal population.63 The studies are listed in Table 18. 

The incidence of ovarian cancer is higher in postmenopausal women relative to benign 

gynecologic conditions, which also increase CA-125 levels. This should translate into a greater 

accuracy of CA-125 test performance in this population. Indeed, all test parameters except NPV 

are both higher and the range narrower in postmenopausal women. The lowest PPV was 0.73, 

with the remaining above 0.85, which is significantly higher than the range of PPV observed in 

studies that did not stratify their results by menopausal status. The NPV is lower in the 

postmenopausal population, despite the higher sensitivity, because of a greater prevalence of 

cancer in this population. CA-125 is consistently more helpful in discriminating benign from 

malignant lesions in postmenopausal women compared with premenopausal women. 

Table 18. CA-125 results stratified by menopausal status 

Study Threshold Premenopausal Postmenopausal 

Sens Spec PPV NPV Sens Spec PPV NPV 

Malkasian et al., 

1988136 > 100 

> 35 

0.60 

0.60 

0.95 

0.73 

0.67 

0.29 

0.93 

0.91 

0.77 

0.81 

0.97 

0.91 

0.98 

0.94 

0.72 

0.74 

Gadducci et al., 

199696 > 65 0.67 0.91 0.67 0.91 0.80 1.00 1.00 0.69 

Gadducci et al., 

199298 > 64 0.50 0.26 0.05 0.86 0.81 0.86 0.88 0.78 

Franchi et al., 

199595 > 39 0.73 0.64 0.24 0.94 0.77 0.85 0.87 0.74 

Patsner and 

Mann, 1988151 > 35 0.63 0.78 0.66 0.76 0.77 0.81 0.85 0.72 

Dowd et al., 

199355 > 35 0.74 0.73 0.60 0.84 0.86 0.82 0.90 0.76 

Finkler et al., 

198856 > 35 0.50 0.69 0.35 0.81 0.84 0.92 0.94 0.80 

Schutter et al., 

199863 > 35 -- -- -- -- 0.69 0.84 0.73 0.81 

Antonic and 

Rakar, 199571 > 35 0.67 0.92 0.40 0.97 0.87 0.93 0.93 0.87 

Abbreviations: CA-125 = cancer antigen 125; NPV = negative predictive value; PPV = positive predictive value; Sens 

= sensitivity; Spec = specificity

Other Serum Markers 

The fact that CA-125 is < 35 U/ml in 20 percent of women with early stage ovarian cancer, 

has motivated research into other serum based tests. We identified 13 articles that described a 

total of 17 different sera studies in women with an adnexal mass. Some studies investigated the 

performance of other tumor-associated antigens such as tumor-associated glycoprotein 72 (TAG72) or CA-19-9. Although most of the tumor-associated antigens achieved specificities of 
70

approximately 0.82 to 0.92, the sensitivity, PPV, and NPV were overall lower than those 

reported for CA-125. Two studies investigated carcinoembryonic antigen (CEA),114,157 and 

although they employed slightly different thresholds, the sensitivity reported in both (0.16 and 

0.22) are so poor as to lead both authors to conclude that assessment of CEA in the evaluation of 

an adnexal mass is not helpful. Roman et al.42 investigated whether the addition of human 

chorionic gonadotropin (hCG), alpha-fetoprotein (AFP), and lactate dehydrogenase (LDH) to 

CA-125 improved the test performance. In their series the sensitivity of CA-125 alone was 0.67, 

the specificity was 0.71, PPV 0.35, and NPV 0.90. The addition of the other three tests did not 

change the test results very much. The combined test (defined as any of the markers positive) 

sensitivity was 0.72, its specificity was 0.70, PPV 0.36, and NPV 0.94. AFP, hCG, and LDH do 

not appear to improve the diagnostic performance of CA-125. 

Gadducci et al. investigated the role of D-Dimer in a series of 121 women with adnexal 

masses.96 The sensitivity for D-Dimer alone was 0.91, the specificity was 0.83, the PPV 0.82, 

and the NPV 0.92 – making D-Dimer one of the best performing tests identified in our review. 

Stratifying by menopausal status showed a greater performance in premenopausal women where 

the sensitivity, specificity, PPV and NPV were 1.00, 0.91, 0.75, and 1.00 respectively (n = 57). 

For postmenopausal women they were 0.89, 0.65, 0.85, and 0.72, respectively. Chalas et al. 

investigated the role of elevated platelets in 241 women.31 The specificity and PPV were similar 

to that reported for D-Dimer (0.84 and 0.83, respectively), but the sensitivity and NPV were 

significantly lower (0.56 and 0.59). These two studies are intriguing, but the results need to be 

established in future studies to better assess their possible contribution to the evaluation of 

adnexal masses. 

Aside from D-Dimer, none of the studies contained information making stratification by 

menopausal status possible. In conclusion, none of the sera markers investigated in this review 

appears to perform better than CA-125, with the possible exception of D-Dimer in the 

premenopausal population. 

Population-based Studies 

Almost all of the studies identified were case series. There were, however, 13 populationbased screening studies included in this review. They are listed in Table 19. Although all of the 

women included in these studies did not have a diagnosis of an adnexal mass at the time of 

enrollment, these studies are included here because they highlight some important issues about 

test performance. The strongest studies from a methodological perspective were those by 

Marchetti et al.,140 Vuento et al.,186 DePriest et al.,34 Adonakis et al.,51 and Tailor et al.171 

Marchetti, Vuento, Tailor and DePriest all used ultrasound as a screening modality. In all of 

these studies, the PPV was low, ranging between 0.006 to 0.07. Screening with CA-125 yielded 

a slightly higher PPV of 0.17.51 Tailor et al.171 offered followup screening within the same 

populations. In the first screening episode, which captured the total study population of 2,500 

women, the test characteristics were similar to those reported in the other screening studies. The 

test characteristics improved, however, with subsequent screening. Women who had a negative 

screen were offered either a 12- or 6-month repeat ultrasound (depending on individual risk 

factors). Nine hundred and ninety-eight women received a second ultrasound screening. For this 

subset, the PPV improved to 0.21. For women screened greater than two times, the PPV was 

0.25. However, not all women offered additional screening returned for the ultrasound. This 

potential bias was not discussed by the authors, and it is unclear how it may have influenced the 
71

performance of repeat screening. The three studies by Kurjak et al. each had various biases that 

could have accounted for their markedly different reported test performances. One did not report 

followup on test negatives and therefore included no false negative in the series,126 another study 

population was an undescribed subset of a larger still incomplete screening series,127 and the last 

study did not describe inclusion criteria.128 Van Nagell et al.49 screened 14,469 women with 

ultrasound. They reported their results 12 months from the time of screening. However they 

note that four women were diagnosed with cancer greater than 12 months after screening. These 

women had all screened negative and were included in their analysis as true negatives. 

Reclassifying these individuals as false negatives changes the sensitivity from 0.81 to 0.68. 

Table 19. Population-based screening studies 

Study N Test Sensitivity Specificity PPV NPV 

Marchetti et al., 

2002140 4350 Ultrasound screening: criteria 

NR 

Operative cases only (n = 45) 

Assuming all negatives were 

truly negative (n = 4359) 

1.00 

1.00 

0.37 

0.96 

0.07 

0.01 

1.00 

1.00 

Menon et al., 

2000145 1027 Ultrasound 

Volume > 8.8 ml 

Abnormal morphology 

Complex morphology 

0.90 

1.00 

0.84 

0.94 

0.94 

0.97 

0.21 

0.24 

0.37 

1.00 

1.00 

0.98 

Vuento et al., 

1995186 1364 Combined ultrasound 

morphology and Doppler (PI 

< 1.0) 

1.00 0.88 0.006 1.00 

DePriest et al., 

199336 24/3220 Ultrasound morphology 

(DePriest) 

Operative cases only (n = 24) 

1.00 0.71 0.33 1.00 

Kurjak et al., 

1992126 83/1000 RI < 0.41 

Ultrasound morphology 

(unique score) 

Presence of random vessels 

Combined ultrasound and 

Doppler 

0.96 

0.48 

0.90 

0.90 

0.95 

0.98 

0.98 

0.94 

0.90 

0.93 

0.96 

0.90 

0.98 

0.78 

0.95 

0.94 

Kurjak et al., 

1994127 32/5013 Ultrasound “persistent mass” 

Ultrasound assuming all test 

negatives true negatives 

1.00 

1.00 

0.97 

0.99 

0.80 

0.80 

1.00 

1.00 

Kurjak et al., 

1991128 680/ 

8620 

RI < 0.4 0.96 0.99 0.98 1.00 

DePriest et al., 

199734 90/6470 Ultrasound morphology 

(DePriest) (n = 90) 

Assuming all test negatives 

true negatives (n = 6470) 

1.00 

0.86 

0.59 

0.99 

0.17 

0.07 

1.00 

1.00 

Adonakis et al., 

199651 2000/ 

2000 

CA-125 > 35 

PE “palpable mass” 

1.00 

0.67 

0.99 

0.97 

0.17 

0.03 

1.00 

1.00 

Andolf et al., 

199052 801 Combined ultrasound and 

BME (both positive for test to 

be positive) 

Ultrasound and BME criteria 

not well described 

1.00 0.94 0.11 1.00 

Jacobs et al., 

198858 1010 CA-125 > 30 U/ml 

BME 

Ultrasound (ovarian volume > 

8.8ml) (n = 58 for ultrasound) 

1.00 

1.00 

1.00 

0.97 

0.97 

0.74 

0.03 

0.04 

0.08 

1.00 

1.00 

1.00 

Tailor et al., 

2003171 2500 Ultrasound morphology 

(descriptive) 

0.86 0.97 0.07 1.00 
72

Study N Test Sensitivity Specificity PPV NPV 

N = 2500 

Ultrasound for second 

screening episode (n = 998) 

Ultrasound for >= third 

screening episode (n = 733) 

1.00 

1.00 

0.99 

0.99 

0.21 

0.25 

1.00 

1.00 

van Nagell et 

al., 200049 14469 Ultrasound (ovarian volume > 

20 cm3 for premenopausal 

women, > 10 cm3

 for 

postmenopausal women) 

0.81 0.99 0.09 1.00 

Abbreviations: BME = bimanual examination; CA-125 = cancer antigen 125; NR = not reported; PE = pelvic 

examination; PI = pulsatility index

Methodological Issues 

In reviewing the literature on evaluation modalities, numerous methodological problems 

consistently reduced our ability to draw conclusions about the performance of various tests both 

individually and in comparison with each other. Some of these problems concerned study 

design, others related to statistical issues. 

Patient population. With the exception of the 13 population-based screening studies, all of 

the articles were case series. Some were consecutive and others non-consecutive. Some were 

based on operative cases within a specific time frame at one or several institutions, whereas 

others were referral series, often located in oncology clinics. The path to diagnosis was almost 

never described, making it difficult to asses the generalizability of the results. Further, age was 

the only patient characteristic that was reliably documented. Other characteristics, such as 

family history, were almost never included. This has several implications. The 

overrepresentation of operative cases especially from academic facilities, likely overrepresents 

the prevalence of malignancy in the study populations when compared with the population of 

women with adnexal masses in general. It also exaggerates the performance of the evaluative 

modalities, especially in regards to sensitivity and PPV. Finally, it limits the generalizability of 

the evidence. 

Definition of malignant. There was inconsistency between studies regarding whether the 

malignant classification included any malignancy or whether it included only ovarian 

malignancies. The inclusion of all malignancies would exaggerate the test’s specificity and PPV 

at the expense of its sensitivity and NPV. From a practical standpoint, this difference may not be 

that problematic, as all malignancies are important. However, this classification bias increased 

the heterogeneity of test performance and limits generalizability. Finally, almost all of the 

articles that reported series containing tumors of low malignant potential (LMP) (also called 

borderline) classified these tumors as malignant. This changes the reported performance of the 

various evaluative modalities in these studies. There were three studies identified where 

stratification by LMP was possible. These are listed in Table 20. Classifying LMP tumors as 

malignant increases the specificity and PPV relative to classifying them as benign, while 

decreasing the specificity and NPV. Overall, PPV tended be somewhat low (even in populations 

with high prevalences of disease). The inclusion of LMP tumors into the malignant category 

inflated this measurement somewhat. Obviously, because of uncertainty about the natural 

history of LMP tumors, the most appropriate way of classifying them as part of diagnostic test 
73

evaluation is also uncertain. Given this uncertainty, ideally investigators would report results 

using alternative methods of classifying LMP tumors. 

Table 20. Effect of classification of LMP tumors as malignant or benign on diagnostic test characteristics 

Study Test LMP classified as malignant LMP classified as benign 

Sens Spec PPV NPV Sens Spec PPV NPV 

Roman et al., 

1998157 CEA 0.16 0.93 0.35 0.83 0.19 0.93 0.25 0.90 

Wakahara et al., 

2001187 Ultrasound 

morphology 

CA-125 

0.82 

0.45 

0.82 

0.86 

0.65 

0.74 

0.92 

0.63 

0.86 

0.77 

0.78 

0.61 

0.54 

0.37 

0.95 

0.90 

Timmerman et al., 

1999178 CA-125 0.80 0.82 0.63 0.91 0.77 0.79 0.56 0.91 

Abbreviations: CA-125 = cancer antigen 125; CEA = carcinoembryonic antigen; LMP = low malignant potential 

(tumors); NPV = negative predictive value; PPV = positive predictive value; Sens = sensitivity; Spec = specificity

Variability in test criteria. Of the 69 articles that evaluated ultrasound morphology, only 

31 used established scoring criteria; 38 used a novel method. This resulted in a great 

heterogeneity of tests for ultrasound morphology and contributed to the range in performance 

noted. Many of the studies employed purely descriptive analysis to arrive at a benign versus 

malignant diagnosis. This limits the reproducibility of those results. Many of the scoring 

systems and descriptive categories had never been independently verified, and the paucity of 

details regarding what constituted a positive test makes such verification impossible. In terms of 

ultrasound evaluation by color Doppler, there was also a range of reported thresholds. Some of 

the variability in test criteria reflects the limitations of ultrasound technology. However, such 

differences limited the comparability between studies. 

Masses as numerator. While most studies examined persons as the unit of 2-by-2 analysis, 

there were many studies that analyzed their data by masses. Even though the number of persons 

in the study was usually reported, it was often impossible to reconfigure the 2-by-2 table to refer 

to persons not masses. This was especially true in the radiology literature. This influenced the 

comparability between studies. 

Menopausal status. Most of the studies did describe the patient population in terms of age. 

We were able to calculate the proportion of menopausal patients in most studies. However, the 

results were rarely reported in a way that allowed stratification by menopausal status. Where 

stratification was possible, a difference in test performance was seen. The heterogeneity in test 

performances was magnified by the different proportions of pre- and postmenopause in the 

different study populations. 

Sample size. Few studies discussed sample size issues, potentially leading to inappropriate 

conclusions, especially regarding comparability of test characteristics. 

Failure to account for observer variability. No studies attempted to account for the effects 

of observer variation on the precision of estimates, although a few did calculate interobserver 

coefficients. For tests where the thresholds for normal and abnormal were based on either 

qualitative assessments (such as descriptions of ultrasound morphology) or quantitative measures 

(such as ultrasound morphology scores), this variability will have implications for the precision 

of sensitivity and specificity. 
74

Prevalence and predictive value. We did not limit our analysis of test characteristics to 

studies from the United States. As the incidence of ovarian cancer is different in different 

countries, this influences the range of predictive values reported in the literature. Locations with 

low disease prevalence will have low PPVs compared with higher prevalence areas. The 

heterogeneity of study locations influenced the range of reported test characteristics and 

somewhat limits the comparability of the results. 

Summary 

Table 21 summarizes the pooled sensitivity and specificity estimates for CA-125 and the 

various imaging modalities. 

Table 21. Pooled sensitivity and specificity estimates 

Diagnostic Test Pooled Sensitivity (95% CI) Pooled Specificity (95% CI) 

ULTRASOUND: MORPHOLOGY 

Scoring system: Sassone 0.86 

(0.79 to 0.91) 

0.77 

 (0.73 to 0.81) 

Scoring system: DePriest 0.91 

(0.84 to 0.95) 

0.68 

(0.49 to 0.82) 

Scoring system: Ferrazzi 0.87 

(0.80 to 0.92) 

0.81 

(0.62 to 0.91) 

Scoring system: Finkler 0.82 

(0.65 to 0.91) 

0.78 

(0.59 to 0.91) 

Other 0.86 

(0.82 to 0.89) 

0.83 

(0.76 to 0.88) 

ULTRASOUND: DOPPLER 

Resistive index 0.72 

(0.61 to 0.82) 

0.90 

(0.84 to 0.94) 

Pulsatility index 0.80 

(0.74 to 0.85) 

0.73 

(0.62 to 0.81) 

Maximum systolic velocity 0.74 

(0.56 to 0.86) 

0.81 

(0.59 to 0.83) 

Presence of vessels 0.88 

(0.80 to 0.92) 

0.78 

(0.65 to 0.87) 

MORPHOLOGY PLUS DOPPLER 0.86 

(0.79 to 0.91) 

0.91 

(0.80 to 0.97) 

MRI 0.91 

(0.86 to 0.94) 

0.87 

(0.83 to 0.90) 

CT 0.90 

(0.83 to 0.94) 

0.75 

(0.36 to 0.94) 

FDG-PET 0.67 

(0.52 to 0.79) 

0.79 

(0.70 to 0.85) 

CA-125 

(threshold > 35) 

0.78 

(0.75 to 0.81) 

0.78 

(0.71 to 0.82) 

Abbreviations: CA-125 = cancer antigen 125; CI = confidence interval; CT = computed tomography; FDG = 18-

Fluorodeoxyglucose; MRI = magnetic resonance imaging; PET = positron emission tomography

The use of established scoring systems in the evaluation of an adnexal mass by ultrasound 

morphology appears to perform slightly better than simple descriptive assessment. However, 

there does not appear to be a benefit of one scoring system over another. Based on small 

numbers of studies, 3D ultrasound shows some improvement over 2D. Although the pooled 
75

sensitivity and specificity of MRI was the highest of any imaging modality, its performance was 

less consistent in studies where it was directly compared to other modalities such as CT and 

ultrasound. 

Color Doppler assessment by RI, PI, and maximum systolic velocity are not superior to the 

more simple assessment of the presence or absence of arterial vessels within the mass. The 

efficacy of RI, PI, and maximum systolic velocity are hampered by the overlap in values of these 

measurements between benign and malignant masses. 

Combined ultrasound morphology and color Doppler assessments have higher sensitivity and 

specificity compared to either alone. Although ultrasound morphologic evaluation by a 

gynecologist appears to be as reliable as that performed by a radiologist, there was no evidence 

of Doppler measurements done outside of the context of a radiology referral. 

In postmenopausal women, an elevated CA-125 is useful for helping rule in ovarian cancer. 

Qualitatively, there was a consistent trade-off across all tests between sensitivity and 

specificity. 

The relatively low PPVs in all of the tests are particularly striking given that many of the 

included studies were done in preoperative patients; the likely “screening” done prior to a 

decision for surgery suggests that the PPV of a particular test in the initial evaluation of an 

adnexal mass is likely to be even lower. 

Question 4: Explicit Scoring Systems 

Question 4 is: What is the accuracy of explicit scoring systems which incorporate various 

combinations of imaging findings, patient risk factors, and/or CA-125 levels for detecting 

malignancy? Have these scoring systems been applied to a population of women before 

laparoscopy or laparotomy? 

Approach 

Explicit scoring systems were sought in the medical literature from among all studies of 

diagnostic assessment of adnexal or pelvic masses. We considered only scoring systems that 

combined data from more than one category of the following types of information: (1) imaging 

findings; (2) patient risk factors; and (3) laboratory data. Clinical prediction rules that utilized 

data entirely from only one category (for example, ultrasound based morphological indices56) are 

described as part of Question 3. 

Imaging findings could include: (1) ultrasound based tests, such as transabdominal or 

transvaginal 2D ultrasound or Doppler ultrasound; (2) radiographic tests, such as CT; or (3) other 

imaging studies, such as MRI or PET scans. 

Patient risk factors include menopausal status, age, or other risk factors. 

Laboratory data was primarily CA-125, but we recorded data on other serum tumor markers 

as well. 
76

Results of Literature Search and Screening 

We identified 36 studies that met the inclusion criteria.42,48,51-

53,55,62,63,66,72,86,87,97,103,105,116,134,135,138,139,147,169,178,180,181,185,202-211 These are described in Evidence 

Table 4 (Appendix D*

). 

Study Characteristics 

Scoring systems identified. The scoring systems were of several types. The most common 

were models developed using statistical modeling techniques such as logistic regression (or 

artificial neural networks) to develop estimates for predicted probability of malignancy. Such 

estimates were then used to construct clinical prediction rules (e.g., the Risk of Malignancy 

Index [RMI], which calculates a numeric score based on CA-125 level multiplied by a 

menopausal score and an ultrasound morphology score) and decision thresholds (e.g., for RMI, 

the most common threshold is 200). Other scoring systems used simple combinations of criteria 

based on individual modalities, which were then combined using Boolean and or or (e.g. CA125 > 65 U/ml and ultrasound morphology score > 10 points). Some models were validated in 

separate populations from the data set used to develop the scoring systems either described as 

part of its initial development, or in subsequent publications by the original developers or others. 

Types of data incorporated. The most common scoring systems used ultrasound, CA-125 

and menopausal status. Some type of ultrasound data was used in all 36 publications; studies 

varied with regard to the type of ultrasound technology that was used. All used 2D ultrasound to 

evaluate morphology, some using transabdominal and many using transvaginal probes. Studies 

that used Doppler ultrasound used a variety of parameters, including measures as simple as 

detection of flow, or as complex as specific indices derived from Doppler-measured flow rates, 

such as the RI or PI. Many described scoring rules based on combinations of features of 

morphology (Finkler score) or combined morphology and blood flow. 

CA-125 was a component of the scoring system in 30 reports; other serum tumor markers 

included CA-72-4, incorporated into two reports,53,63 and the markers AFP, LDH, and hCG, were 

used in one report.42 All studies that used these other serum markers also used CA-125. 

Menopausal status was incorporated into scoring systems of 19 reports. The definition of 

menopausal status varied across studies, and in a few cases age was used as a proxy for clinically 

determined menopausal status. Three studies included only postmenopausal women,62,63,135 and 

thus could not use this variable in the scoring system. 

Physical examination was a component of scoring systems in six reports.42,51-53,62,63

Type of study populations. Most study populations were case series assembled at the time 

of referral for surgery and collected either at the point of preoperative ultrasound imaging or 

preoperative surgical evaluation. No studies were based in primary care clinical populations. 

One study described evaluation of adnexal masses detected during an ovarian cancer screening 

program.51

Reporting of study populations. Menopausal status of the study populations was described 

in 28 of the 36 reports; three reports included only postmenopausal women.62,63,135

 

* Appendixes cited in this report are provided electronically at 

http://www.ahrq.gov/downloads/pub/evidence/pdf/ adnexal/adnexal.pdf.
77

Age was reported for the study population as a mean or median in 18 of 36 studies; it was 

reported in categories in one additional study. Symptom status was seldom described in the 

candidate reports. 

Race/ethnicity was not reported in any of the studies. 

Risk factors for ovarian cancer (besides menopausal status and age, describe above) were not 

reported, except in one study that reported the proportion of the study population that was 

nulliparous versus multiparous.138 

Methodology. The methodological quality of the included studies may be described as 

follows: 

Reference standard (handling of borderline). Some studies, particularly those assembled at 

the time of ultrasound investigation rather than surgery, encountered women with masses due to 

simple cysts with low risk of malignancy. Two studies allowed use of an operative report in lieu 

of histopathology as a reference standard,87,116 and one used clinical followup without surgery as 

an alternate reference standard.48

Verification bias. Fourteen studies failed to verify disease status for all or a significant 

sample of test-negative women. 

Test reliability. Only nine studies provided data on the reliability of test assessments. 

Sample size. Only 11 of the reports described a priori recruitment targets or sample size 

calculations. We excluded studies with fewer than 50 women; however, some studies report 

subgroup analyses with fewer than 50 women, for example, the subset of postmenopausal 

women in Strigini et al.169

Use of appropriate statistical tests. The majority of reports (n = 28) used appropriate 

statistical analysis of the diagnostic data; however seven reports reported inadequate analyses. 

Blinding. None of the reports described the use of techniques to blind investigators to the 

disease status of study patients. 

Definition of positive and negative test. Most studies (n = 24) provided a priori definitions of 

a positive and negative test result; studies failed to meet this criterion most often when no 

explicit threshold was set a priori, but it was set based on study data. 

Explicit validation method. Half of the reports (18/36) used some explicit validation method; 

many of the reports replicated previously described scoring systems in a new population. In 

many cases, these studies described new scoring systems which were not always validated. 

The most common validation method was replication in a separate population. Two studies 

used validation techniques within a single study population: one split-sample,209 and one 

bootstrap.205

Diagnostic Accuracy of Scoring Systems 

This section considers the diagnostic accuracy of the RMI (Jacobs 1990) and subsequent 

replications and refinements (RMI2, RMI3, Jacobs 1993, and Timmerman models). 

RMI. The first scoring system based on a statistical model was published in 1990;116 it has 

been replicated in 11 subsequent clinical populations.55,72,87,139,147,180,204,206-208,210 The diagnostic 

performance in these 12 studies is shown in Figure 17. 

The RMI is a clinical prediction rule based on ultrasound, CA-125, and menopausal status 

data defined as follows: 
78

RMI = U x M x CA-125 

where ultrasound (transabdominal) is scored 1 point for each of the following 

characteristics: multilocular cyst, evidence of solid areas, evidence of metastases, 

presence of ascites, and bilateral lesions. 

U = 0 for ultrasound score of 0 

 = 1 for ultrasound score of 1 

 = 3 for ultrasound score ≥ 2 

CA-125 = Serum CA-125 in U/ml 

Menopausal status 

M = 1 if premenopausal 

 = 3 if postmenopausal 

In the initial report, Jacobs et al.116 used the cutoff value of 200. At this cutpoint, sensitivity 

was 85 percent and specificity was 97 percent among a population of 143 women undergoing 

surgical investigation for an adnexal mass. The performance of the initial model (study 6 in 

Figure 17) has, in most studies, failed to be equaled in subsequent attempts at validation. Three 

of the subsequent 11 studies have similar performance (studies 7, 9, 10 in Figure 17).72,87,208 It is 

notable that these three studies have fewer quality features (n ≤ 4) than the other eight studies (n 

≥ 5 of 7 quality features). 

When sensitivity and specificity are combined separately using a random-effects model, the 

pooled sensitivity is 0.78 (95% CI, 0.72 to 0.84) and the pooled specificity is 0.90 (0.81 to 0.95). 
79

Figure 17. Performance of RMI model of Jacobs et al. (1990)116 in development set (study 6) and subsequent 

validation studies using cutoff score of 200 

Key to Figure 17: 1 = Tingulstad et al., 1996;180 2 = Timmerman et al., 1999;210 3 = Mol et al., 2001;207 4 = Lu et al., 

2003;206 5 = Manjunath et al., 2001;139 6 = Jacobs et al., 1990;116 7 = Davies et al., 1993;87 8 = Morgante et al., 

1999;147 9 = Obeidat et al., 2004;208 10 = Asif et al., 2004;72 11 = Aslam et al., 2000;203 12 = Dowd et al., 199355

RMI2. In 1996, Tingulstad et al.180 reported a refinement to the original RMI scoring 

system, commonly referred to as RMI2. RMI2 is defined identically to RMI except that new 

weights were used for the ultrasound and menopause components as follows: 

U = 1 for ultrasound score of 0-1 

 = 4 for ultrasound score ≥ 2 

M = 1 if premenopausal 

 = 4 if postmenopausal 

A cutoff value of 200 was also recommended for RMI2. Like the RMI, the RMI2 scoring 

system has been replicated.134,139,147,207 The original report of RMI2 found sensitivity of 0.8 and 

specificity of 0.92. Subsequent validation studies have performed no better. These validation 
80

studies all exhibited five or more quality features. The pooled sensitivity of all five studies is 

0.77 (0.71 to 0.82), and pooled specificity 0.89 (0.85 to 0.91). The summary ROC curve is 

shown in Figure 18. 

Figure 18. Performance of RMI2 model of Tingulstad et al. (1996)180 in development set (2) and subsequent 

validation studies using cutoff score of 200 

Key to Figure 18: 1 = Andersen et al., 2003;202 2 = Tingulstad et al., 1996;180 3 = Manjunath et al., 2001;139 4 = Ma et 

al., 2003;134 5 = Morgante et al., 1999;147 6 = Aslam et al., 2000203

RMI3. Subsequently, a further refinement to the RMI and RMI2 was reported by Tingulstad 

et al.211 This third scoring system is defined identically to RMI and RMI2 except that new 

weights were used for the ultrasound and menopause components as follows: 

U = 1 for ultrasound score of 0-1 

 = 3 for ultrasound score ≥ 2 

M = 1 if premenopausal 

 = 3 if postmenopausal 
81

A cutoff value of 200 was also recommended for RMI3. The RMI3 scoring system has been 

replicated in one additional study.139 The original report of RMI3 found sensitivity of 0.71 and 

specificity of 0.92, while the validation study reported very similar performance, with sensitivity 

of 0.74 (0.65 to 0.83) and specificity of 0.91 (0.83 to 0.99). 

Tailor and subsequent replications. Tailor et al.209 reported a scoring system based on an 

artificial neural network method that was based on a small population of 67 women total, 15 of 

whom had malignancies. Unlike the RMI family of systems described above, this system did not 

include CA-125, but considered age, menopausal status, and a variety of ultrasound 

morphological features and Doppler indices. While this system reported using 52 cases as a 

training set and 15 cases as a test set, the performance of the system was reported only for the 

study population as a whole: sensitivity 0.93 (95% CI, 0.81 to 1.0) and specificity 1.0 (0.94 to 

1.0). Subsequently four studies have replicated this system showing markedly poorer diagnostic 

performance (Figure 19) when applied to separate populations, consistent with over-fitting in the 

initial model development.185,203,204,207

Figure 19. Performance of model of Tailor et al. (1999)209 in development set (4) and subsequent validation 

studies 

Key to Figure 19: 1 = Mol et al., 2001;207 2 = Valentin et al., 2001;185 3 = Aslam et al., 2000;203 4 = Tailor et al., 

1999;209 5 = Aslam et al., 2000204
82

Twenty other scoring systems have been described, none of which has been as extensively 

replicated as the systems described above. Five of these other scoring systems have been 

validated in one other population as shown in Table 22; each of the systems was based on 

ultrasound morphology, CA-125, Doppler, and menopausal status. The models were: 

Timmerman LR1,178,210 Timmerman AAN1,178,207 Timmerman AAN2,178,207 Timmerman 

LR2,178,207 and Jacobs 1993.207,212 

Table 22. Performance of other scoring systems at initial derivation and subsequent replication in another 

population 

Initial Sensitivity (95% CI) Specificity (95% CI) 

description 

Subsequent 

validation Initial 

development 

Replication Initial estimate Replication 

Timmerman 

LR1210 Valentin 2001185 0.87 (0.79 to 0.97) 

0.62 

(0.44 to 0.80) 

0.92 

(0.87 to 0.97) 

0.79 

(0.68 to 0.90) 

Timmerman 

AAN1178 Mol et al. 2001207 0.94 (0.87 to 1.0) 

0.90 

(0.79 to 1.0) 

0.90 

(0.85 to 0.96) 

0.60 

(0.52 to 0.68) 

Timmerman 

AAN2178 Mol et al. 2001207 0.96 (0.90 to 1.0) 

(0.91 

0.90 

(0.79 to 1.0) 

0.94 

(0.89 to 0.98) 

0.46 

(0.38 to 0.54) 

Timmerman 

LR2178 Mol et al. 2001207 0.96 (0.90 to 1.0) 

0.90 

(0.79 to 1.0) 

0.86 

(0.79 to 0.92) 

0.56 

(0.48 to 0.64) 

Jacobs 1993212 Mol et al. 2001207 0.85 

(0.74 to 0.96) 

0.90 

(0.79 to 1.0) 

0.97 

(0.94 to 1.0) 

0.61 

(0.53 to 0.69) 

In each case, the initial diagnostic performance described by the system significantly 

degrades on replication in another population (Figure 20). 
83

Figure 20. Performance of various other scoring systems in development and validation studies in separate 

populations 

Arrows indicate change in performance estimate from development (start of arrow) to validation (end of arrow) for 

paired studies of each scoring system. 

Key to Figure 20: 1-4 = Timmerman et al., 1999;210 5-8 = Mol et al., 2001;207 9 = Jacobs et al., 1993;212 10 = Valentin 

et al., 2001185

Ten additional systems were described in seven reports.42,48,53,63,181,203,205 Most of these 

studies used logistic regression or artificial neural network modeling methods to derive a new 

model. One used bootstrap validation techniques,205 but none was validated in another study 

population. One of these studies203 reported on newly fitted logistic regression models created 

by forcing variables that were include in previously described scoring systems.178,209,213 Aslam et 

al.204 constructed three separate models based on each possible pairwise combination of the three 

previously described models. The diagnostic performance of these miscellaneous unvalidated 

models is shown in Figure 21. 
84

Figure 21. Performance of various other unvalidated models 

Key to Figure 21: 1 = Twickler et al., 1999;48 2-3 = Biagiotti et al., 1999;205 4 = Torres et al., 2002;181 5 = Schutter et 

al., 1998;63 6 = Balbi et al., 2001;53 7 = Roman et al., 199742

Thirteen further reports describe the diagnostic performance of simple rules for combining 

single test or single modalities into a decision rule.42,51,52,62,63,66,86,97,103,105,135,138,169 None of these 

criteria has been validated in another population. Each of these studies used dichotomous rules 

for two or more tests (or modalities) and then combined them using a simple rule like “malignant 

if any test positive” (Boolean or) or “malignant if all tests positive” (Boolean and). Some of the 

studies reported diagnostic performance of several different simple rules. 

Twelve of these studies used ultrasound and CA-125, five incorporated physical exam, two 

included other serum tumor markers42,63 and one used age over 50 years.138

Six of these studies reported results for postmenopausal women separately: in three studies, 

the entire study population was postmenopausal62,63,135 while three studies reported diagnostic 

performance for the postmenopausal subgroup separately.103,105,169 The diagnostic performance 

of 18 simple combination rules in these six studies is shown in Figure 22. 
85

Figure 22. Performance of unvalidated simple combination rules in postmenopausal women only 

Key to Figure 22: 1-4 = Maggino et al., 1994;135 5-8 = Schutter et al., 1998;63 9-11 = Schutter et al., 1994;62 12-13 = 

Strigini et al., 1996;169 14-17 = Guerriero et al., 1998;103 18-19 = Guerriero et al., 2002105

In contrast, the diagnostic performances of 17 simple combination rules in studies that 

include both premenopausal and postmenopausal women in the study population are shown in 

Figure 23. 
86

Figure 23. Performance of unvalidated simple combination rules in mixed pre- and postmenopausal 

populations

Key to Figure 23: 1-2 = Andolf et al., 1990;52 3-4 = Adonakis et al., 1996;51 5-9 = Mancuso et al., 2004;138 10 = 

Gadducci et al., 1988;97 11-12 = Chou et al., 1994;86 13 = Alcazar et al., 1999;66 14-15 = Roman et al., 1997;42 16-17 

= Strigini et al., 1996169

The results show a wide range of sensitivity and specificity. This variation reflects 

differences in decision thresholds (e.g., CA-125 > 35 U/ml versus CA-125 > 65 U/ml) and in the 

rules for combining tests (e.g., use of Boolean or versus and when combining results of two or 

more tests). 

Discussion 

No scoring systems were both developed and validated expressly for evaluating adnexal 

masses in postmenopausal women. Existing scoring systems that have been validated have all 

been developed in mixed pre- and postmenopausal populations. Those scoring systems that have 

been described in populations of postmenopausal women were neither rigorously developed 

(they consist of simple combination rules) nor validated in other populations. 
87

The highest demonstrated specificity obtained with these scoring systems appears to be in the 

range of 90 to 95 percent and, at this range of specificity, the sensitivity appears to be in the 

range of 65 to 80 percent. However, as suggested by the performance in the few populations of 

postmenopausal women studied, the same degree of sensitivity and specificity is unlikely to be 

possible. Reliable estimates of the diagnostic performance of scoring systems cannot be 

determined from these studies. 

This review of scoring systems demonstrates several important limitations of predictive 

models and has important implications for the clinical usefulness of these models and the future 

research in this area of inquiry. First, validation in an external population is critical to obtain 

accurate estimates of diagnostic performance, because all modeling techniques lead to 

overestimation of diagnostic performance in the data from which it was derived. This 

overestimation of diagnostic performance is clearly demonstrated by comparing the development 

and validation studies described for RMI, Tailor, and other scoring systems (Figures 17-20). The 

studies described here suffer from being relatively small for modeling; reliable variable selection 

and parameter estimation requires at least 10 to 15 cases (in this case, ovarian malignancies) for 

every term selected in a predictive model. Few, if any, met this statistical rule of thumb. This 

limitation is particularly apparent in the case of the Tailor model, where subsequent studies 

demonstrated a high degree of overestimation of the original model. Third, these studies used 

populations that were identified following referral for surgery in most cases, after some filtering 

had already occurred. Furthermore, these studies failed to describe the initial presentation 

(symptomatic or asymptomatic, palpable or non-palpable mass) of women eventually enrolled. 

Thus, the applicability of these studies to women in primary care, where an adnexal mass is often 

first noted, is uncertain. 

Question 5: Monitoring Women with 

Suspected Benign Masses 

Question 5 is: Among women with suspected benign masses on initial investigation, what 

are the sensitivity and specificity of monitoring with periodic CA-125 and/or interval ultrasound 

examinations for detecting malignant masses? How does the interval of testing/definition of 

change affect sensitivity and predictive value? 

Approach 

For each study we sought to identify a population of patients with a screening abnormality 

which was “probably benign” and which the authors felt did not meet criteria for immediate 

surgical intervention. We then attempted to define the outcomes of further testing in the defined 

population, including the results of subsequent testing and final clinical outcome as defined by a 

pathology report or extended clinical followup. The interpretation of results is limited by the 

narrow scope of Question 5. Specifically, it is often difficult to identify a subgroup of patients 

with a screening abnormality which could be defined as a “suspected benign lesion” within 

larger screening studies. Often, results are not stratified with respect to these sub-populations, 

making it difficult to calculate sensitivity and specificity of the followup testing. In addition, by 

definition, it is also difficult to estimate the “sensitivity” of a followup regimen. We assumed 
88

that this refers to detection of cancer as part of the followup regimen, and that women with 

cancer diagnosed outside of the followup were “false negatives.” 

Results 

We identified nine articles meeting the criteria for this question;40,127,135,145,214-218 these are 

summarized in Table 23, with details in Evidence Table 5 (Appendix D*

). Five were populationbased screening studies of asymptomatic, postmenopausal patients without known ovarian 

masses;40,127,145,214,217 one was a voluntary screening program.216 All addressed to some degree 

the use of interval ultrasound for detecting malignant masses. Although several used CA-125 as 

part of their followup, none reported any results based on the use of interval CA-125 in a 

population with adnexal lesions. None addressed the effects of changing the interval of testing 

on sensitivity and predictive value; the disparate nature of the studies prohibited any inferences 

on the effect of test interval on sensitivity. 

Table 23. Studies of followup regimens for benign-appearing lesions 

Study Population N Followup 

interval 

Length of 

followup 

Loss to 

followup 

True/false 

positives 

detected 

during 

followup 

Cancers 

missed 

Population-based studies (followup of “benign” masses identified in screening) 

Menon 

et al., 

200145

Followup of 

scans 

considered 

“equivocal” 

17 “Equivocal” 

scans followed 

every 6 weeks 

until clearly 

normal or 

abnormal; normal 

scans followed 

with CA-125 

every 3 months 

Median 

6.8 years 

Not reported 1 cancer/5 

benign 

lesions 

 0 (1 within 6 

weeks of 

initial test, 

before first 

followup 

scan) 

Modesitt 

et al., 

200340

Followup of 

simple cysts 

< 10 cm 

2,763 TVUS every 3-6 

months for 

simple cysts 

Mean 6.3 

years 

Not reported 7 cancers/0 

benign 

lesions 

3 cancers, 

none 

developed in 

the original 

cyst 

Schincaglia et 

al., 

1994217

Followup of 

postmenopausal 

ovaries > 9 

cc, or with 

simple cyst 

347 If cyst: followed 

with ultrasound 

every 6 months; 

if change, 

referred; others: 

referral if 

unchanged at 3 

and 6 months 

“At least” 

1 year 

Not 

reported, but 

all had “at 

least 1 year” 

2 cancers/96 

benign 

lesions 

None in 249 

not referred 

Kurjak 

et al., 

1994127

Followup of 

postmenopausal 

women with 

simple cyst 

> 2.5 cm but 

< 5 cm, 

resistive 

88 (of 

404 

with 

simple 

cysts) 

Repeat 

ultrasound every 

6 months 

6 months Not reported 1/17 with 

benign 

lesions 

0 

 

* Appendixes cited in this report are provided electronically at 

http://www.ahrq.gov/downloads/pub/evidence/pdf/ adnexal/adnexal.pdf.
89

Study Population N Followup 

interval 

Length of 

followup 

Loss to 

followup 

True/false 

positives 

detected 

during 

followup 

Cancers 

missed 

index ≥ 4.1) 

Castillo 

et al., 

2004214

Followup of 

postmenopausal 

women with 

simple cyst 

< 10 cm 

215 Repeat 

ultrasound and 

CA-125 in 3 

months, then 

every 6 months 

Median 27 

months 

30.6% 0/44 benign 

masses 

1 

Case series (clinical history prior to identification of mass not routinely described) 

Valentin 

and 

Akrawi, 

2002218

Followup of 

postmenopausal 

women with 

low score on 

ultrasound 

malignancy 

risk scale 

162 Repeat 

ultrasound 3, 6, 

9, and 12 

months, then 

every 12 months; 

test positive if 

increase in size 

or cyst more 

complex 

Median 3 

years 

0 (cancer 

and mortality 

tracked 

through 

registry) 

0 cancers/7 

patients 

underwent 

surgery for 

change 

0 

Maggino et 

al., 

1994135

Followup of 

postmenopausal 

women with 

cysts < 5 

cm, thin wall, 

no septae, 

no free fluid 

45 Details on 

followup strategy 

not reported 

Not 

reported 

4.4% 0/0 0 

Levine 

et al., 

1992216

Followup of 

voluntary 

screening of 

postmenopausal 

women with 

unilocular 

simple cyst 

32 Repeat 

ultrasound every 

3 months x 1 

year, then every 

6 months 

“Over half 

at least 

one year” 

22.2% 0/0 0 

Goldstein et 

al., 

1989215

Followup of 

postmenopausal 

women with 

simple cysts 

≤ 5 cm 

16 Repeat 

ultrasound 

(abdominal) 

Mean 29 

months 

6 (12% of 

original 48) 

0/2 with 

benign 

lesions 

0 

Abbreviations: CA-125 = cancer antigen 125; TVUS = transvaginal ultrasound

Menon et al.145 performed a large prospective screening study of 22,000 postmenopausal 

women older than 45 years. Initial screening consisted of CA-125; patients with CA-125 ≥ 30 

underwent endovaginal ultrasound evaluation. Results were interpreted as normal (ovarian 

volume < 8.8 ml/normal morphology), equivocal (volume < 8.8 ml, abnormal morphology), or 

abnormal (volume ≥ 8.8 ml). Normal morphology was defined as uniform hypoechogenicity and 

smooth outline. Abnormal morphology was defined as simple cysts or complex lesions. Patients 

with normal scans were triaged to repeat CA-125 every 3 months for a year and subsequently 

returned to yearly screening; median followup was 6.8 years, with loss to followup not reported. 

Patients with abnormal scans were referred to a gynecologist for consideration of surgical 

intervention. Patients with equivocal scans were triaged to repeat ultrasound at 6-week intervals 

until a scan could be classified as normal or abnormal. Of 741 patients who were triaged to 
90

ultrasound, 20 (2.7 percent) index cancers were identified. We focused on the group of patients 

with “equivocal” scans who were triaged to interval testing in an attempt to answer the study 

question. There were 17 equivocal scans. Of these, nine had simple cysts which were followed 

and did not result in a cancer diagnosis (true negatives). One patient died of pneumonia prior to 

her first repeat ultrasound, and one died of advanced ovarian cancer prior to her first repeat 

ultrasound; this cancer death could possibly be considered a false negative for the followup 

strategy, although it could also be considered a false negative from the original study since the 

death occurred within 6 weeks of the initial scan. Six patients were scheduled for surgery 

following an equivocal scan, presumably due to abnormal followup ultrasound. One of these had 

ovarian cancer (true positive), and the other five had benign disease (false positive). Because the 

number of equivocal scans was so small, and because the classification “equivocal” does not 

necessarily imply that the lesions were felt to be “suspected benign” as designated in Question 5, 

it is not possible to calculate the sensitivity and specificity of prolonged monitoring strategies 

using this study. The authors do not draw any conclusions regarding the appropriateness of 

interval testing. 

Modesitt et al.40 performed a large screening study of 15,106 asymptomatic women at least 

50 years old without a history of ovarian cancer. Patients were screened with TVUS. Criteria 

for abnormality were ovarian volume > 10 ml and any morphologic abnormality, including 

simple or complex cysts. Patients with abnormal TVUS were triaged to repeat TVUS in 4 to 6 

weeks, with Doppler flow ultrasound, CA-125 level, and tumor morphology indexing performed 

at the second visit. Patients with simple unilocular cysts which were considered likely benign 

were triaged to repeat TVUS every 3 to 6 months. Mean followup was 6.3 years. Two thousand 

and seven hundred and sixty-three (2,763) women were diagnosed with 3,259 unilocular cysts. 

Spontaneous resolution of unilocular cysts occurred in 2,261 (69.4 percent) of lesions. Ten 

patients subsequently developed ovarian cancer. Seven of these had additional abnormal areas 

which subsequently developed on TVUS (considered true positives because they were 

subsequently identified by interval testing). Two developed ovarian cancer after the cyst in 

question had resolved on sonographic followup (these might be considered false negatives). One 

patient developed cancer in the ovary opposite the cyst being followed (this might also be 

considered a false negative). Calculated on a per-patient basis, the sensitivity and specificity of 

followup testing in the population with a simple unilocular ovarian cyst are 70 percent (95% CI, 

41.6 to 98.4 percent) and 100 percent (99.9 to 100 percent), respectively. Because none of the 

unilocular cysts subsequently developed into a cancer, the sensitivity and specificity improve to 

100 percent (57.1 to 100 percent) and 100 percent (99.9 to100 percent), respectively, when 

calculated on a per-lesion basis. Followup time is a major strength of this study. The authors 

conclude that unilocular ovarian cysts are associated with a very low risk of malignancy and can 

be safely followed with serial ultrasound. 

Schincaglia et al.217 performed a screening study of 3,541 asymptomatic postmenopausal 

patients. All patients underwent transabdominal ultrasonography with assessment of ovarian 

volume and morphology. Patients were divided into four groups based on the results of the 

initial ultrasound. All patients with ovarian volume > 15 ml (Group 4) were referred for repeat 

“level II” ultrasonography for morphologic assessment and fine needle aspiration (FNA) when 

feasible. Patients with ovarian volume between 9 and 15 ml (Group 3) were triaged to followup 

ultrasound at 3 and 6 months. Patients with ovarian volume < 9 cm but a cystic appearance 

(Group 2) were triaged to followup ultrasound in 6 months. Patients with ovarian volume < 9 ml 

and homogeneous appearance (Group 1) were considered negative and had no further 
91

intervention. Clinical followup at 1 year and pathology results if surgery was performed were 

considered the reference standard. Two hundred and eighty-three (283) patients (Groups 2 and 

3) were deemed appropriate for followup using repeat ultrasound at 3- to 6-month intervals 

without the need for immediate referral for FNA/surgery. Of these 283 patients, 34 subsequently 

developed concerning ultrasound findings and were referred for a level II scan and/or possible 

FNA. The clinical results of this group of 34 are not given separately. Of the 249 who had nonconcerning followup scans, none developed cancer with followup of at least 1 year (“true 

negatives”). Therefore, the specificity of ultrasound followup is 100 percent (95% CI, 98.8 to 

100 percent) for patients with an initial abnormal but “probably benign” ultrasound. Sensitivity 

within this group cannot be calculated with the information given in the publication. The ability 

to answer Question 5 would be enhanced if specific outcomes of each of the four groups defined 

by the authors had been given. The study was also limited by the fairly short followup interval 

and the lack of prior or concurrent validation of the ultrasonographic groups defined in the study. 

Kurjak et al.127 screened 5,013 women 40 years old or older (30.6% postmenopausal), of 

whom 404 had simple cysts with a diameter between 2.5 and 5 cm and a resistive index greater 

or equal to 0.41. These women received a followup scan in 6 months. Investigators reported the 

results of 88 women for whom the 6-month scan results were available. The definition of change 

prompting further diagnosis was not explicitly described. Of the 88 women, 18 ultimately 

underwent surgery based on the findings at 6 months, with one cancer detected and 17 benign 

lesions. Results stratified by menopausal status were not provided. This study was limited by 

lack of details on clinical decision rules, and short followup. 

Castillo et al.214 screened 8,794 postmenopausal women; 215 had simple unilocular cysts less 

than 10 cm in diameter. Twelve percent of these masses were asymptomatic. These women 

underwent repeat ultrasound and CA-125 in 3 months, with subsequent followup studies every 6 

months. Progression was defined as an increase in diameter of 1 cm or more, regression as a 

decrease of 1 cm, and resolution as absence of the cyst at 2 consecutive visits 6 months apart. 

Median followup was 27 months. There was one interval ovarian cancer between studies, and 44 

women had benign masses removed. Although this study was among the highest quality studies 

in terms of reporting of relevant data, it is limited by the relatively small size and the high loss to 

followup (30.6%). 

The remaining four studies135,215,216,218 were all small (less than 200 patients), and of variable 

quality (Table 23). None reported any interval cancers in patients receiving followup, or cancers 

detected during followup. The study of Valentin et al.218 was notable for length of followup 

(median 3 years) and complete ascertainment of followup status using Swedish cancer and death 

registry data. 

 

Discussion 

There are limited data available to support a global definition of “probably benign” ovarian 

lesions or to support a specific method of interval testing to identify ovarian malignancy among 

patients in whom such lesions have been identified. For the most part, studies are limited by 

small size, variable length of followup, variable definitions of significant change and thresholds 

for intervention, and methods for followup. 

The question of how best to define and evaluate “sensitivity” of followup regimens is a 

difficult one. Several factors need to be considered. First, interval cancers presenting between 

the initial study and the first followup visit may well be considered false negatives of the initial 
92

study; alternatively, they may reflect a too-long followup interval. Second, given the lack of data 

on the natural history of ovarian cancer, it is unclear whether cancers developing in benignappearing lesions represent subclinical cancers present at the time of the initial diagnosis, or new 

cancers representing malignant transformation of a benign cyst. If the latter, then the ultimate 

success of any followup regimen may depend as much on the natural history of a given 

malignancy as on the sensitivity and specificity of the tests used for followup. Finally, cancers 

identified during followup should ideally have high survival rates (although whether such high 

survival rates would reflect the efficacy of the followup or the biology of cancers which are 

associated with benign-appearing cysts is unclear). The number of cancers identified in the 

reviewed studies was too small to draw any inferences about relative survival. 

Overall, only two interval cancers occurred during followup in the studies identified (one 

prior to the first followup scan), and 10 cancers were identified during followup. As noted, an 

additional three cancers developed after resolution of a cyst or in the contralateral ovary. The 

highest quality study40 provides good evidence for the safety of prolonged followup with 

interval TVUS at 3- to 6-month intervals for patients with unilocular ovarian cysts of up to 10 

cm in diameter, and the findings of the other studies are consistent with this conclusion. 

Question 6: Surgical Morbidity and Mortality 

Question 6 is: Among women with adnexal masses, what are the morbidity and mortality 

from diagnostic surgery (laparoscopy or laparotomy)? At what point does the risk of surgery 

outweigh the risk of detecting malignancy? 

Approach 

We searched the literature for studies that reported the morbidity and mortality of surgical 

management of adnexal masses. We also used the Nationwide Inpatient Sample (NIS) discharge 

database, maintained by the Agency for Healthcare Research and Quality (AHRQ), to obtain 

estimates of morbidity and mortality associated with diagnostic laparoscopy or exploratory 

laparotomy for a range of diagnoses associated with adnexal masses. The NIS is limited to 

inpatient procedures and does not cover ambulatory surgical centers, where some adnexal masses 

are likely to be managed, especially those masses thought to have a low likelihood of cancer. In 

addition to surgical complications, we also examined articles that provided data on the test 

characteristics of frozen section pathologic diagnosis; especially in the setting of minimally 

invasive procedures, false negative results on frozen section might lead to suboptimal surgical 

management and delayed therapy, while false positive results might lead to more extensive 

surgery than necessary, with possible implications for increased surgical morbidity and affects 

on ovarian function. 
93

Results of Literature Search and Screening 

We identified 24 articles that met our inclusion criteria;32,37,41,219-239 these are summarized in 

Evidence Table 6 (Appendix D*

). Twenty-two articles reported on the morbidity and mortality 

of surgical management of adnexal masses.32,37,41,219-234,237-239 In addition, two of the included 

articles reported on the sensitivity and specificity of frozen section;220,236 false negative frozen 

section results could lead to inadequate surgical management and delayed treatment, while false 

positive results could lead to more extensive surgery than necessary. Finally, one of the 

included articles addressed the potential effect of conservative surgery for removal of an ovarian 

cyst resulting from endometriosis (endometrioma) on subsequent fertility.235

Methodological Quality of Included Studies 

Size of population. None of the papers provided a description of the referral base; two32,37

were limited to gynecologic oncology practices. Lack of information on the referral base 

prevents assessment of generalizability. Since all of these studies were performed in centers 

experienced in laparoscopic surgery, the generalizability may well be limited. 

Number of cases. Five studies had fewer than 200 cases, with correspondingly wide 

confidence intervals for reported event rates. Two studies had larger numbers of cases, 683230

and 757.219 However, the study by Marana et al.230 was limited to women under 40. 

Patient selection. None of the studies reported how patients were referred to the surgical 

practices. All provided criteria for laparoscopic management of masses, based on various 

criteria to suggest high or low risk of malignancy. We found two trials where patients were 

randomized to laparoscopy or laparotomy,224,225 but randomization methods were not well 

described. 

Application of reference standard. In this sense, “reference standard” refers to the method 

by which a complication was diagnosed. Only two studies described followup beyond 8 weeks, 

but they did not detail whether all patients underwent similar followup protocols. 

Results 

There were three deaths in one study of 146 patients (all undergoing laparoscopy), and none 

in any of the other studies (a total of 5,599 patients). Pooling all patients, the mortality was 0.05 

percent, with a 95% CI of 0.01 to 0.17 percent. 

Table 24 shows the results from individual studies. The two randomized studies224,225 both 

showed lower morbidity with laparoscopy compared to laparotomy, although only one of them224

had sufficient power to show a statistically significant difference. Although the study of 

Deckardt and colleagues224 was randomized, there were substantial differences in the procedures 

performed in each arm. Laparoscopy patients tended to undergo more conservative procedures: 

they were significantly more likely to have cystectomy (60.0 vs. 20.2 percent), less likely to have 

oophorectomy (0.8 vs. 20.2 percent), and less likely to have bilateral salphingo-oophorectomy 

(4.0 vs. 21.4 percent). Both studies where laparoscopy was directly compared to laparotomy 

showed increased complication rates (primarily postoperative complications) among the 

 

* Appendixes cited in this report are provided electronically at 

http://www.ahrq.gov/downloads/pub/evidence/pdf/ adnexal/adnexal.pdf.
94

laparotomy patients. The four non-randomized studies all showed higher morbidity rates with 

laparoscopy, but there were substantial differences in patient selection criteria. 

In series of laparoscopy cases, morbidity rates ranged from 0.9 percent to 22.1 percent (Table 

24); series differed widely in their selection criteria for laparoscopic management of the mass. 

Few stratified results based on menopausal status; in some cases, postmenopausal patients were 

explicitly excluded. In one study where multivariate analysis was performed to assess for risks 

of morbidity, performance of additional procedures (hysterectomy) significantly increased the 

risk of morbidity, while a history of hysterectomy increased the likelihood of conversion to 

laparotomy (presumably because of increased technical difficulty secondary to postoperative 

adhesions).226

Table 24. Morbidity in series of patients undergoing surgical management of adnexal masses 

Study N Patient population Complication rate 

(95% CI) 

Notes 

Randomized trials of laparoscopy versus laparotomy 

Deckardt et al., 

1994224 192 22.4% laparoscopy, 

26.4% laparotomy 

postmenopausal 

Laparotomy: 30.3% 

(21.8 to 42.3%) 

Laparoscopy: 11.2% 

(6.8 to 18.7%) 

“Randomized,” but some 

differences between two 

arms 

3.5% conversion 

Fanfani et al., 

2004225 100 Laparoscopy: 10% 

postmenopausal 

Laparotomy: 20% 

postmenopausal 

Laparotomy 6% (1.8 to 

17.5%) 

Laparoscopy 0% (0 to 

10.6%) 

No malignancies 

Small sample size 

Non-randomized comparisons 

Hidlebaugh et 

al., 1997227 405 199 laparoscopy 

206 laparotomy 

20.2% postmenopausal 

Laparotomy 27.2% 

(21.8 to 34.0%) 

Laparoscopy 2.5% (1.0 

to 6.0%) 

Selection criteria for 

laparoscopy not defined 

Potential other risk factors 

for complications not 

described 

Yuen et al., 

1997239 110 Laparotomy: 6% 

postmenopausal 

Laparoscopy: 3.8% 

postmenopausal 

Laparotomy 28% (18.5 

to 43.1%) 

Laparoscopy: 9.6% 

(4.2 to 21.8%) 

Difference between 

complication rates 

attributable to higher number 

of postoperative 

complications in laparotomy 

group 

Carley et al., 

2002221 106 44 laparotomy 

62 laparoscopy 

Menopausal status not 

reported 

Laparotomy 4.6% (0.7 

to 16.7%) 

Laparoscopy 0% (0 to 

8.6%) 

Chapron et al., 

1997222 186 121 laparoscopy, 

65 laparotomy 

43% postmenopausal 

Laparotomy: 15.4% 

(8.9 to 27.0%) 

Laparoscopy: 8.3% 

(4.6 to 15.0%) 

Patients with high suspicion 

of malignancy went directly 

to laparotomy 

Results not analyzed by 

“intention to treat”—19 of 

laparotomy patients started 

as laparoscopy 

13.6% of laparoscopies 

converted to laparotomy 

Laparoscopy only 

Childers et al., 

199632 138 Not described in detail; 

age range 9-91 

10.1% (6.2 to 16.7%) Length of followup not given 

for benign cases 
95

Study N Patient population Complication rate 

(95% CI) 

Notes 

Gynecologic oncology 

service 

Results not stratified by age 

or menopausal status 

8.0% conversion to 

laparotomy 

Canis et al., 

1994219 757 11.4% postmenopausal 1.1% (0.53 to 2.1%) Mean followup 42 months 

(range 3-153 months) 

Dottino et al., 

199937 160 53% postmenopausal 7.5% (4.3 to 12.9%) Gynecologic oncology 

service 

Marana et al., 

2004230 620 All less than 40 years 

old 

0.9% (0.4 to 2.0%) Mean followup 30 months 

Single surgeon 

Parker et al., 

199441 61 100% postmenopausal 3.3% (0.4 to 12.3%) Masses “presumptively 

benign” based on imaging, 

exam, clinical history 

4.9% conversion 

Sadik et al., 

1999232 220 3.2% postmenopausal 0.9% (0.06 to 3.5%) Malignant masses “excluded 

from study” 

Chi et al., 

2004223 146 Menopausal status not 

reported; median age 

54 

Mortality 2.5% (0.5 to 

6.3%) 

Morbidity 22.1% (15.1 

to 32.7%) 

Clinical history not 

described—not clear if other 

conditions besides adnexal 

mass included 

Havrilesky et al., 

2003226 396 37.2% postmenopausal Laparoscopy 8.3% (6.0 

to 11.6%) 

Risk of complication 

increased with concurrent 

hysterectomy 

Lok et al., 

2000228 513 5.5% postmenopausal Laparoscopy 13.3% 

(10.6 to 16.6%) 

No malignancies 

75.% symptomatic 

Mann and Reich, 

1992229 44 100% postmenopausal Laparoscopy 4.6% (0.7 

to 16.7%) 

1/44 had cancer 

Parker and 

Proietto, 1997231 86 Menopausal status not 

reported 

Laparoscopy 22.1% 

(15.1 to 32.7%) 

1/86 had cancer 

Serur et al., 

2001233 100 49% postmenopausal Laparoscopy 10% (5.6 

to 19.0%) 

- 

Shalev et al., 

1994234 55 100% postmenopausal Laparoscopy 10.9% 

(5.2 to 22.9%) 

- 

Tarik and Fehmi, 

2004237 1478 Menopausal status not 

reported (but mean age 

30) 

Laparoscopy: 

Diagnostic procedures 

1.8% (0.8 to 3.8%) 

Minor procedures: 

1.4% (0.8 to 2.3%) 

Proportion with preoperative 

diagnosis of adnexal mass 

not reported 

Van Herendael 

et al., 1995238 121 Menopausal status not 

reported 

Laparoscopy: 1.7% 

(0.1 to 6.4%) 

- 

Abbreviation: CI = confidence interval

Nationwide Inpatient Sample 

Table 25 shows the estimated numbers of discharges in the United States in 2000-2001 under 

each diagnostic class and procedure (standard errors not shown for simplicity). The results 

illustrate the difficulty in using discharge data to attempt to estimate morbidity and mortality 

rates for surgical procedures. Both morbidity and mortality are highest for cancer diagnoses, but 
96

there is no way to determine the extent to which the underlying disease process contributed to 

either complications or death; for example, “exploratory laparotomy” or “diagnostic 

laparoscopy” in many ovarian cancer patients likely represents a “second-look” procedure done 

to determine response to chemotherapy. Outcomes of these procedures are not relevant to 

estimating the risks of a primary diagnostic procedure. The laparoscopies that are included in the 

NIS are likely not representative of all laparoscopies for adnexal masses; since the NIS does not 

capture surgeries performed at ambulatory surgery centers, the cases within the NIS may 

represent those for which surgeons had a higher index of suspicion of malignancy, or anticipated 

higher technical difficulty. Another major limitation is the inability to distinguish between the 

initial indication for surgery and the final diagnosis. Finally, in order to try to eliminate 

confounding by additional procedures, we excluded cases in which hysterectomy was performed 

– however, because hysterectomy is part of the standard initial surgical treatment of ovarian 

cancer, many cases of initial management are excluded. 

Table 25. Estimated U.S. discharges for exploratory laparotomy and diagnostic laparoscopy with discharge 

diagnoses consistent with adnexal mass, with mortality and complication rates 

Number of 

discharges 

Died Mortality 

rate 

Complications Complication rate 

OVARIAN CANCER 118,042 7099 6.0% 515 0.4% 

Laparoscopy (no ovarian procedures) 222 5 2.3% 0 0.0% 

Laparoscopy plus conservative ovarian 

procedure 27 0 0.0% 0 0.0% 

Laparoscopy plus oophorectomy 16 0 0.0% 0 0.0% 

Laparotomy (no ovarian procedure) 566 11 1.9% 5 0.9% 

Laparotomy plus conservative ovarian 

procedure 68 0 0.0% 0 0.0% 

Laparotomy plus oophorectomy 36 0 0.0% 0 0.0% 

OTHER ADNEXAL CANCER 780 15 1.9% 5 0.6% 

Laparoscopy (no ovarian procedures) 0 0 0.0% 0 0.0% 

Laparoscopy plus conservative ovarian 

procedure 0 0 0.0% 0 0.0% 

Laparoscopy plus oophorectomy 0 0 0.0% 0 

Laparotomy (no ovarian procedure) 15 15 100.0% 0 0.0% 

Laparotomy plus conservative ovarian 

procedure 0 0 0% 0 

Laparotomy plus oophorectomy 0 0 0% 0 

BENIGN OVARIAN NEOPLASM 145,024 255 0.2% 964 0.7% 

Laparoscopy (no ovarian procedures) 1,560 5 0.3% 35 2.2% 

Laparoscopy plus conservative ovarian 

procedure 75 0 0.0% 0 0.0% 

Laparoscopy plus oophorectomy 24 0 0.0% 0 0.0% 

Laparotomy (no ovarian procedure) 700 4 0.6% 16 2.3% 

Laparotomy plus conservative ovarian 

procedure 72 0 0.0% 0 0.0% 

Laparotomy plus oophorectomy 31 0 0.0% 0 0.0% 

PELVIC MASS 13,625 30 0.2% 60 0.4% 

Laparoscopy (no ovarian procedures) 

Laparoscopy plus conservative ovarian 

procedure 41 

Laparoscopy plus oophorectomy 

Laparotomy (no ovarian procedure) 35 5 14.3% 

Laparotomy plus conservative ovarian 

procedure 

Laparotomy plus oophorectomy 

OVARIAN CYSTS 474,485 376 0.08% 3045 0.6% 
97

Number of 

discharges 

Died Mortality 

rate 

Complications Complication rate 

Laparoscopy (no ovarian procedures) 5,508 0.00% 65 1.2% 

Laparoscopy plus conservative ovarian 

procedure 274 0.00% 0.0% 

Laparoscopy plus oophorectomy 173 0.00% 0.0% 

Laparotomy (no ovarian procedure) 1,429 79 5.53% 19 1.3% 

Laparotomy plus conservative ovarian 

procedure 99 0.00% 0.0% 

Laparotomy plus oophorectomy 86 0.00% 0.0% 

PARA-OVARIAN CYST 21,807 5 0.0% 92 0.4% 

Laparoscopy (no ovarian procedures) 271 0.0% 0.0% 

Laparoscopy plus conservative ovarian 

procedure 24 0 0.0% 0 0.0% 

Laparoscopy plus oophorectomy 9 0 0.0% 0 0.0% 

Laparotomy (no ovarian procedure) 61 10 16.4% 0 0.0% 

Laparotomy plus conservative ovarian 

procedure 5 0 0.0% 0 0.0% 

Laparotomy plus oophorectomy 5 0.0% 0.0% 

PELVIC INFLAMMATORY DISEASE 430,027 439 0.1% 4793 1.1% 

Laparoscopy (no ovarian procedures) 7,184 4 0.1% 150 2.1% 

Laparoscopy plus conservative ovarian 

procedure 445 0 0.0% 9 2.0% 

Laparoscopy plus oophorectomy 159 0 0.0% 5 3.1% 

Laparotomy (no ovarian procedure) 2,129 10 0.5% 53 2.5% 

Laparotomy plus conservative ovarian 

procedure 160 0 0.0% 0 0.0% 

Laparotomy plus oophorectomy 45 0 0.0% 0 0.0% 

NORMAL PELVIS 108.8 0 0 0 0 

Other Outcomes 

We identified two studies that reported on the sensitivity and specificity of intraoperative 

frozen section done to determine pathologic diagnosis.220,236 They reported similar findings. 

Both studies defined low malignant potential tumors as cancer. Canis et al.220 reported a 

sensitivity of 92.2 percent and a specificity of 92.2 percent in 141 women (29.8 percent 

postmenopausal, 35 percent with cancer or low malignant potential tumors). Tangjitgomol et 

al.236 estimated similar values, with a reported sensitivity of 91.3 percent and specificity of 93.3 

percent in 212 women (menopausal status not reported, cancer prevalence 77 percent). Defining 

low malignant potential cancers as benign decreased sensitivity in both cases. 

We identified only one article that addressed the potential impact of surgical management of 

benign cysts on fertility. Somigliana et al.235 followed 32 women who received ovarian 

stimulation after removal of an endometriotic cyst. The mean number of follicles observed in the 

ovary where the cyst had been removed (2.0 ± 1.5) was significantly lower than in the 

contralateral ovary (4.2 ± 2.5), suggesting that the surgical procedure may have led to decreased 

ovarian reserve. An alternative explanation is that the cyst itself had an adverse effect on ovarian 

reserve. 
98

Discussion 

Ideally, reports of adverse outcomes of diagnostic surgery for adnexal masses would be 

divided into four separate categories, based on preoperative symptoms and postoperative 

findings: (1) women with symptomatic masses which ultimately proved malignant; (2) women 

with symptomatic masses which ultimately proved benign; (3) women with asymptomatic 

masses which ultimately proved malignant; and (4) women with asymptomatic masses which 

ultimately proved benign. For the first three groups, the operative procedure could be considered 

appropriate even in the event of morbidity, since there is some benefit (primary surgical therapy 

for malignancy, or management of symptomatic nonmalignant adnexal pathology) to be gained 

from surgical diagnosis and treatment. For women with asymptomatic benign masses, there are 

theoretical benefits for detecting some benign masses, including (1) prevention of subsequent 

malignant transformation, (2) avoidance of rupture which, for certain benign masses 

(endometrioma and mature teratoma) could cause acute symptoms, (3) easier surgical 

management, with fewer complications, compared to management of a larger symptomatic mass, 

(4) avoidance of torsion (twisting of the adnexa) and emergent surgical management and (5) 

avoidance of effects on fertility, either from the underlying condition itself or from more 

extensive surgery for a larger mass. However, we did not identify any evidence for these 

benefits; the probabilities of these potential benefits also would differ widely depending on the 

underlying pathology and natural history of a particular mass, the patient’s age and reproductive 

status, and other comorbidities. 

Unfortunately, neither the literature nor available discharge data allow estimates of the 

probabilities of outcomes based on initial presentation. In the case of the literature, this is 

because of a lack of reporting of the clinical path by which patients come to undergo surgery. In 

the case of discharge data, it is because of the inherent limitations of the International 

Classification of Diseases, Ninth Revision (ICD-9) coding. Even if more recent data on 

ambulatory surgery were available, it would still be limited by coding. 

Summary 

Mortality for laparoscopic management of adnexal masses at experienced centers appears to 

be quite low, although the upper bound of this low rate is unclear. 

Patient characteristics that determine risk of morbidity are unclear, although the need for 

more extensive procedures appears to increase the risk. Laparoscopy may have a lower 

morbidity rate than laparotomy, but this appears to be due, at least in part, to different patient 

selection criteria and surgical procedures performed. 

Two small studies suggest that the false negative rate of intraoperative frozen section 

diagnosis is approximately eight percent, and the false positive rate is approximately five to 

seven percent. Whether either type of false result has a significant impact on outcome is unclear. 

There is suggestive evidence that removal of a cyst in premenopausal women may affect 

ovarian reserve, potentially affecting fertility and/or age of menopause, but the underlying 

pathologic process may also play a role. More data are needed. 

There are no data to allow estimation of the risks of a diagnostic procedure in the patient with 

an asymptomatic mass, or to assess the benefits of surgery in that patient compared to the risk of 

malignancy. 
99

Question 7: Modeling Diagnostic Strategies 

Question 7 is: What are the estimated trade-offs resulting from various strategies for 

evaluation of the adnexal mass? 

Approach 

A formal decision analytic approach is often quite helpful for synthesizing evidence coming 

from a range of sources, of varying quality, and of varying degrees of precision in estimates. 

Such models are also helpful in identifying which parameters are most important, in order to 

prioritize future research. Ideally, the underlying natural history of the disease in question can be 

modeled, with the impact of subsequent clinical interventions estimated based on test 

characteristics, effectiveness and morbidity from treatment, patient preferences, etc. In addition, 

the effect of varying both the incidence and natural history of ovarian cancer based on risk 

factors such as genetic predisposition can also be taken into account if adequate data are 

available. For example, such models have been quite helpful in exploring the impact of various 

interventions for cervical cancer prevention.240 In addition, data from currently ongoing trials of 

ovarian cancer screening will also provide valuable data on natural history. 241

Because of the methodological limitations of the literature on management of adnexal masses 

cited in the previous sections, a formal decision analysis does not seem appropriate at this time. 

In order to illustrate some of the key areas for future research, we did a simple estimate of the 

expected outcomes of several strategies for evaluation of the adnexal mass based on the findings 

of this review. Because models will ultimately need to incorporate the natural history of ovarian 

cancer, either to evaluate screening or to estimate the consequences of false negative diagnoses, 

we also performed a literature review of existing models of the natural history of ovarian cancer 

and the impact of screening or testing and developed an alternative model. 

Predicting Outcomes of Management Strategies 

As an example, we can consider one clinical scenario: an asymptomatic postmenopausal 

woman undergoing a routine bimanual pelvic examination. If the bimanual examination is 

abnormal, she can undergo a variety of additional tests. We compared several strategies: (1) 

performing CA-125 only, then operating on women with values greater or equal to 35;(2) 

performing an ultrasound with Doppler velocimetry (the strategy with highest sensitivity and 

specificity in our review) and operating on women with positive results both morphologically 

and with Doppler; (3) performing CA-125, then performing ultrasound with Doppler on women 

with elevated CA-125 and operating on women with positive ultrasounds; (4) performing 

ultrasound with Doppler first, then performing CA-125 on women with positive ultrasound 

results, and operating on women with elevated CA-125, and (5) performing both ultrasound and 

CA-125 and combining these results with menopausal status to use the RMI (discussed in detail 

under Question 4); women with RMI scores above the threshold undergo surgery. Strategies 3 

and 4 are examples of serial testing, Strategy 5 an example of parallel testing. Table 26 provides 

estimates for key parameters based on the previous chapters; estimates for test characteristics are 

taken from the point estimates of the pooled random-effects models. 
100

Table 26. Estimates for key model parameters 

Parameter Value 

Prevalence of adnexal masses in postmenopausal women (Question 1) Malignant: 0.1% 

Benign: 1.0% 

Sensitivity of the pelvic examination to detect adnexal masses (Question 2) 0.45 

Specificity of the pelvic examination to detect adnexal masses (Question 2) 0.90 

Sensitivity of combined morphology and Doppler (Question 3) 0.86 

Specificity of combined morphology and Doppler (Question 3) 

Note: We assumed that the specificity of ultrasound for determining the 

absence of pelvic mass was 100%. 

0.91 

Sensitivity of CA-125 in postmenopausal women (Question 3) 0.80 

Specificity of CA-125 in postmenopausal women (Question 3) 0.87 

Sensitivity of RMI (Question 4) 0.74 

Specificity of RMI (Question 4) 0.91 

Abbreviation: RMI = Risk of Malignancy Index

At the initial pelvic examination, the probability of detecting a mass equals: 

 Probability of true positive test + Probability of true negative test, or 

 (Prevalence of mass * Test sensitivity) + (1-Prevalence of mass)*(1-Test 

 Specificity) 

Similarly, the probability of a negative test equals: 

 Probability of true negative + Probability of false negative, or 

 (1-Prevalence)*Test Specificity + Prevalence*(1-Sensitivity) 

At the time of ultrasound, the “prevalence” of disease is equal to the positive predictive value of 

the preceding test, the ultrasound, or: 

 Probability of true positive pelvic/(Probability of true positive pelvic + 

 Probability of false negative pelvic) 

Similar calculations were made for each test or combination of tests. 

Table 27 shows the predicted outcomes (in terms of detected and missed cancers) of testing 

with either ultrasound morphology with Doppler velocimetry or CA-125 alone in a hypothetical 

cohort of 100,000 postmenopausal women. 
101

Table 27. Predicted outcomes of ultrasound plus Doppler or CA-125 testing to determine surgical 

management in a hypothetical cohort of 100,000 postmenopausal women* 

Underlying pathology 

Cancer 

Benign 

mass Normal Total 

Prevalence of 

malignancy 

among test 

positives 

Proportion 

of all tests 

positive 

Missed 

cancers 

Baseline cases 100 1,000 98,900 100,000 0.1% 

Pelvic exam 

Positive 45 450 9,890 10,385 

Negative 55 550 89,010 89615 0.4% 10.4% 55 

STRATEGY: 

CA-125 only 

CA-125 

Positive 36 59 1,286 1,380 

Negative 9 392 8,604 9,005 2.6% 15.3% 9 

Surgery 

Positive 36 36 

Negative 59 1286 1,345 2.6% 

 

STRATEGY: 

Morphology/ 

Doppler only 

Morphology/ 

Doppler 

Positive 39 41 0 80 

Negative 6 410 9,890 10,306 49.8% 0.8% 6 

Surgery 

Positive 39 0 0 39 

Negative 0 41 0 41 49.8% 

* Some numbers may not add up correctly because of rounding. 

Abbreviation: CA-125 = cancer antigen 125

Table 28 shows the predicted outcomes of the serial and parallel testing strategies. 
102

Table 28. Predicted outcomes of serial testing or parallel testing with ultrasound plus Doppler or CA-125 

testing to determine surgical management in a hypothetical cohort of 100,000 postmenopausal women* 

Underlying pathology 

Cancer 

Benign 

mass Normal Total 

Prevalence of 

malignancy 

among 

positive tests 

Proportion 

of all tests 

positive 

Missed 

cancers 

Baseline cases 100 1,000 98,900 100,000 0.1% 

 

Pelvic exam 

Positive 45 450 9,890 10,385 

Negative 55 550 89,010 89,615 0.4% 10.4% 55 

 

STRATEGY: 

CA-125, 

followed by 

morphology/ 

Doppler 

CA-125 

Positive 36 59 1,286 1,380 

Negative 9 392 8,604 9,005 2.6% 13.2% 9 

Morphology/ 

Doppler 

Positive 32 5 0 37 

Negative 4 53 1,286 1,343 86.5% 2.7% 4 

Surgery 

Positive 32 0 0 32 

Negative 0 5 0 5 

STRATEGY: 

Morphology/ 

Doppler 

followed by CA125 

Morphology/ 

Doppler 

Positive 40 41 0 81 

Negative 5 410 9,890 10,305 49.4% 0.8% 5 

CA-125 

Positive 32 5 0 37 

Negative 8 35 0 43 86.5% 45.7% 8 

Surgery 

Positive 32 32 

Negative 0 5 0 5 86.5% 

STRATEGY: 

RMI 

(morphology + 

CA-125 + 

menopausal 

status) 

RMI 

Positive 33 41 0 74 

Negative 12 410 9,890 10,312 44.6% 13.2% 9 

Surgery 

Positive 33 0 0 33 

Negative 0 41 0 41 44.6% 

* Some numbers may not add up correctly because of rounding. 

Abbreviations: CA-125 = cancer antigen 125; RMI = Risk of Malignancy Index 
103

Table 29 summarizes the outcomes of the five strategies in terms of total number of tests, 

total number of missed cancers, and total number of surgeries. 

Table 29. Estimated numbers of tests, missed cancers, and surgeries for each strategy 

Strategies 

Single tests Serial tests Parallel tests 

CA-125 

Ultrasound* CA-125 followed 

by ultrasound 

Ultrasound 

followed by CA-125 

Risk of 

Malignancy Index 

Total tests 10,385 10,385 11,765 10,466 20,770 

Total missed 

cancers 

9 9 13 13 9 

Total surgeries 1,380 80 37 37 74 

Abbreviation: CA-125 = cancer antigen 125

Table 30 illustrates the effect of increasing the prevalence of cancer (for example, in 

symptomatic women with a known mass) from 0.1 percent to 10 percent. The size of the cohort 

here is 1,100 women with masses (the same as in the screening cohort). 

Table 30. Estimated numbers of tests, missed cancers, and surgeries for each strategy in 1,100 women with 

known adnexal mass and underlying prevalence of ovarian cancer 10% 

Strategies 

Single tests Serial tests Parallel tests 

CA-125 

Ultrasound* CA-125 followed 

by ultrasound 

Ultrasound 

followed by CA-125 

Risk of 

Malignancy Index 

Total tests 1,100 1,100 1,317 1,287 2,200 

Total missed 

cancers 

20 15 32 32 26 

Total surgeries 197 184 90 90 155 

Abbreviation: CA-125 = cancer antigen 125

This simple “model” illustrates several key points: 

• The prevalence of malignancy increases as additional diagnostic tests are performed. This is 

certainly clinically appropriate and reflects the effects of sequential testing strategies. 

However, specificity and, to some extent, sensitivity for many of the tests reviewed appear to 

vary with underlying disease prevalence. Thus, estimates for test characteristics calculated at 

one point in the clinical pathway may not be appropriate for other points. 

• Despite a poor sensitivity of 45 percent, the negative predictive value of a negative pelvic 

examination for malignancy is quite high (99.94 percent). The reassurance provided by a 

“normal” exam reflects the epidemiology of the underlying disease, rather than the intrinsic 

value of the test in discriminating benign from malignant. This reflects the low prevalence of 

ovarian cancer in the population. Conversely, the positive predictive value is only 0.4 

percent, despite a specificity of 92 percent. 

• In order to judge the trade-offs between detection of masses that ultimately prove malignant 

compared with the risks of diagnostic surgery, we would need better estimates of morbidity 

and mortality within different diagnostic categories – as noted previously, these do not exist. 

• The most “efficient” strategy in terms of number of tests and surgeries is serial testing with 

ultrasound followed by CA-125; however, this results in four missed cancers compared with 

parallel testing using the RMI. However, parallel testing doubles the number of tests to be 
104

performed. A formal cost-effectiveness analysis requires significantly more data on test 

characteristics and ovarian cancer natural history, as well as the morbidity of surgical 

management. 

• Modeling parallel testing beyond the data in scoring systems is difficult. Besides requiring 

specific assumptions about how results that were positive for one test but negative for 

another would be managed, one would also need to know if the sensitivity and specificity of 

each test were independent or correlated in some way. For example, it seems likely that the 

sensitivity of both ultrasound and CA-125 would be greater for larger masses than for smaller 

masses. 

• In scenarios where the likelihood of ovarian cancer is higher, the negative predictive value of 

any diagnostic strategy will decrease (more missed cancers), and the positive predictive value 

will increase (the proportion of surgical cases where cancer is found will be higher). This is 

seen clearly by comparing Tables 29 and 30. The number of women with adnexal masses is 

the same, but the number of missed cancers is substantially higher with each strategy. 

• In addition, for any screening modality, there needs to be evidence that early detection 

reduces disease-specific morbidity and mortality. In addition, in order to judge the impact of 

false negative results, data on the natural history of ovarian cancer are also needed. Since 

data from large trials are still pending, one way to examine the potential impact of different 

testing strategies for both initial screening and subsequent testing is through the development 

of simulation models. 

We next review published models of the natural history of ovarian cancer. 

Models of Ovarian Cancer: Literature Review 

Four articles were identified from the literature review that used modeling to determine the 

effectiveness and cost-effectiveness of different screening strategies for the detection and 

treatment of ovarian cancer. These are described in Evidence Table 7 (Appendix D*). Studies 

were included if they were directly relevant to Question 7,242-244 or provided natural history 

information that could be used in the construction of a model.245

Schapira et al.242 conducted a decision analysis comparing a one-time screen using 

transvaginal sonography and CA-125 either alone or in combination to determine life-expectancy 

gains in a cohort of 40-year-old women in the United States. In the model women could either 

be screened or unscreened. Probabilities were derived from the literature for the following: 

prevalence of disease in 40-year-old women, percentage of early stage disease, clinical detection 

of disease, sensitivity of the screening test for detection of early stage disease, specificity of the 

screening test, and the mortality rate associated with diagnostic laparotomy. Life expectancy 

was calculated for women who had no disease, early stage disease, and late stage disease. Table 

31 summarizes key input parameters and ranges. 

Assumptions in the model were that survival time for clinically and screen-detected early 

stage disease is the same; morbidity and mortality rates associated with diagnostic laparotomy 

are the same for people with and without the disease; and there is no benefit gained from 

identifying benign disease. 

 

* Appendixes cited in this report are provided electronically at 

http://www.ahrq.gov/downloads/pub/evidence/pdf/ adnexal/adnexal.pdf.
105

The results of the analysis suggested that use of the combined strategy would result in a gain 

in life expectancy (compared to no screening) of one third of a day of life. No screening was 

preferred if the postoperative mortality rate exceeded 7.32 percent or the specificity of the test 

was less than 98.53 percent. An additional analysis, examining the use of testing for women 

aged 65+ suggested that the combined strategy would result in an average gain in life expectancy 

of approximately 3/4 of a day of life. 

Table 31. Key input parameters and ranges for the Schapira model242

Parameter Value Range Source 

Prevalence of ovarian cancer 28.6/100,000 20 to 200/100,000 NCI monograph 

No. 41; 1975 

Percentage of prevalent cases in 

early stage 

50% 20 to 80% Assumed 

Percentage of early stage disease 

diagnosed clinically 

25% 20 to 80% ACS Cancer Statistics 1990 

Sensitivity of CA-125 and TVUS 

(combined) for early stage disease 

45% 20 to 80% Literature review 

Sensitivity of CA-125 and TVUS 

(combined) for late stage disease 

81% 50 to 100% Literature review 

Specificity of CA-125 and TVUS 99.95% 96 to 100% Literature review 

Probability of post-laparotomy death 0.23% 0 to 10% National Halothane Study 

JAMA 1966 

 

Abbreviations: ACS = American Cancer Society; NCI = National Cancer Institute; TVUS = transvaginal ultrasound

Skates and Singer244 developed a stochastic model to evaluate screening with CA-125. Key 

assumptions in this model included: 

• Stepwise progression from Stage I through Stage II through Stage III through Stage IV; 

• Log-normal distributions of progression rates; 

• Stage at clinical detection independent of duration of disease; 

• The coefficient of variation in stage length is constant across all stages; 

• Estimates for the duration of each stage were provided by two gynecologic oncologists. 

In the base case, the model predicted that screening would save 3.4 years of life per detected 

case; of note, estimates for the gains in life expectancy for the entire population undergoing 

screening were not provided. 

Urban et al.243 examined the cost-effectiveness of screening using CA-125 and TVUS alone 

or in combination in a cohort of 1 million 50-year-old women using a stochastic simulation 

model, building on the model of Skates and Singer (Table 32). Screening and case ascertainment 

was assumed to occur over a 3-year period; women were assumed to be followed until age 80 or 

death. 

 
106

Table 32. Key assumptions and data sources used to derive values for parameters in the Urban model243

Parameter Estimate Source 

Stage of ovarian cancer FIGO 

Relative stage lengths (relative to 

Stage 1) 

0.5, 1.333, 0.333 Skates et al.244

FIGO stages III and IV assumed to 

comprise SEER stage 3 

Geometric mean stage length in 

months 

9; 4.5, 12 and 3 months 

Probability of disease during testing 

period 

0.0121 Not stated 

Probability of age at clinical 

detection 

Age 50-54 – 0.153 

Age 55-59 – 0. 184 

Age 60-64 – 0.202 

Age 65-69 - 0.179 

Age 70-74 – 0.150 

Age 75-80 – 0.132 

SEER 

Probability of stage at clinical 

detection 

Stage 1 - 0.223 

Stage 2 - 0.153 

Stage 3/ 4 - 0.624 

SEER 

Point in stage at clinical detection 0.5 of stage length Assumed 

Stage length distribution Log normal (9, 4.5) Assumed 

TVUS sensitivity 100% van Nagell, CA 1990 

van Nagell, CA 1991 

TVUS – false positive 1st screen 0.019; 

2nd screen 0.010; 

3rd screen 0.006 

Campbell, Br J Obstet and Gynecol 

1990 

CA-125 level in cases Refer to page 254 of article for 

formula 

Skates et al.244

Einhorn, Proc Am Soc Clin Oncol 1990 

% of false negatives for CA-125 5% Assumption 

CA-125 specificity in women with 

false positive TVUS 

0.85 Bast, Gyn Onc 1985 

Woolas, JNCI, 1993 

Return to normal life-expectancy 

post-diagnosis 

15 years Assumption 

Probability of death in surgery 

among false-positive 

0.001 Assumption 

Abbreviations: FIGO = International Federation of Gynecology and Obstetrics; SEER = Surveillance, Epidemiology, 

and End Results; TVUS = transvaginal ultrasound

Six screening strategies using TVUS and CA-125 either alone or in combination: annual 

TVUS; annual CA-125, elevated (35U/ml used for referral to laparoscopy); annual CA-125, 

rising or elevated (rising defined as CA-125 level that has doubled since last screen); annual 

TVUS conditional on rising or elevated CA-125; 6-month TVUS condition on rising or elevated 

CA-125; 2-year TVUS conditional on rising or elevated CA-125. Of these, the strategy of 
107

annual TVUS conditional on rising or elevated CA-125 was identified as efficient, meaning it 

saved an equivalent if not higher amount of life at lower costs compared to other strategies. The 

model was especially sensitive to assumptions about the duration of Stage I disease. 

Discussion 

Secondary prevention of cancer mortality through screening has been remarkably effective in 

the case of cervical cancer. Mammography has also reduced mortality from breast cancer, 

although there remains some controversy. To date, although survival in early stage ovarian 

cancer is considerably higher than survival in later stage cancers, trials of screening have not yet 

demonstrated reduction in disease-specific mortality. Although the relative lack of effectiveness 

of ovarian cancer screening to date may reflect the lack of an appropriate test, differences in the 

biology and natural history of the different cancers may also result in some of the differences. 

As outlined in a recent review,246 the most critical criteria for an effective screening strategy 

for ovarian cancer is that there is a time of sufficient duration during the development of ovarian 

cancer when cancer is detectable but in a stage when treatment effectiveness is high. As shown 

in the two most sophisticated models reviewed, estimates of the effectiveness of screening are 

highly dependent on assumptions about the duration of Stage I cancer. The basis for the 

estimates used in both models was the opinion of two clinicians; the methods used to derive 

these estimates were not described. 

Cervical cancer is, in the majority of cases, a squamous carcinoma, which spreads primarily 

through direct extension and secondarily through lymphatic invasion. The most common type of 

ovarian cancer, on the other hand, is typically an adenocarcinoma, which spreads by 

dissemination of tumor cells throughout the peritoneal cavity. 

One assumption commonly made in the models of ovarian cancer we identified is that 

ovarian cancer staging represents the natural history. Figure 24 illustrates a simplified schematic 

model used in all three of the reviewed papers. Patients can develop ovarian cancer, die of other 

causes, or remain healthy. Those who develop ovarian cancer can present with symptoms or 

through testing to become an incident case, or remain undetected, and can either remain within 

the same stage or progress to the next. 
108

Figure 24. Schematic of Markov or stochastic model of ovarian cancer natural history 

Normal

Death from Other

Cause

Stage IV Ov

Cancer

Stage III Ov

Cancer

Stage I Ov Cancer

Stage II Ov

Cancer

Death from

Ovarian Cancer

Although this stepwise progression through stages is the case for cervical cancer, there is no 

evidence to suggest that tumors limited to the ovary (Stage I) must necessarily spread first to 

adjacent pelvic organs (Stage II) prior to spread throughout the peritoneal cavity (Stage III). 

Although staging systems represent the extent of disease, they are developed to help with 

prognosis, and to allow comparison of treatment effectiveness – there is no explicit assumption 

that each stage necessarily must be preceded by the next lowest one. Figure 25 depicts an 

alternative model, which allows some Stage I cancers to progress directly to Stage III: 
109

Figure 25. Alternative model of ovarian cancer history 

Normal

Death from Other

Cause

Stage IV Ov

Cancer

Stage III Ov

Cancer

Stage I Ov Cancer

Stage II Ov

Cancer

Death from

Ovarian Cancer

Using the Markov model described in Chapter 2, we performed sensitivity analyses on 

progression rates and type of progression to determine if this second “model” of progression 

could result in similar stage distributions to observed data. 

Figure 26 compares the predicted incidence of ovarian cancer derived from the model with 

incidence rates reported in the Surveillance, Epidemiology, and End Results (SEER) data set, 

under the assumption that there was a stepwise progression from Stage I through Stage IV: 
110

Figure 26. Model predictions of ovarian cancer incidence (black triangles) compared to SEER incidence 

rates (closed circles) 

We then allowed a proportion of Stage I cancers to proceed directly to Stage III and 

calibrated underlying progression rates. Table 33 compares the model input parameters and 

resulting stage distribution of the two models. 

0

10

20

30

40

50

60

70

35 45 55 65 75 85

Age

Incidence (per 100,000)

2nd Model

SEER
111

Table 33. Inputs and outputs of ovarian cancer models 

 Model 1 (Stage 1 

must progress 

through Stage II) 

Model 2 (some 

Stage I can 

progress 

directly through 

Stage III) 

Stage 

distribution: 

FIGO 

(local data from 

Skates et al.244) 

Stage 

distribution: 

SEER (1995-

2001) 

Parameter estimate 

Annual probability of 

presenting with symptoms: 

Stage I 0.095 0.1 

 

Annual probability of 

presenting with symptoms: 

Stage II 0.095 0.15 

 

Annual probability of 

presenting with symptoms: 

Stage III 0.7 0.9 

 

Annual probability of 

presenting with symptoms: 

Stage IV 1 1 

 

Proportion of Stage I 

progressing directly to 

Stage III 

0 0.25 

Model output: stage 

distribution 

 

FIGO: 

Stage I 19.1% 19.6% 25% 

Stage II 8.2% 9.3% 8% 

Stage III 54.2% 65.2% 52% 

Stage IV 18.6% 5.9% 15% 

SEER/WHO: 

Local 19.1% 19.6% 25% 19% 

Regional 8.2% 9.3% 8% 7% 

Distant and unstaged 72.8% 71.1% 67% 75% 

Abbreviations: FIGO = International Federation of Gynecology and Obstetrics; SEER = Surveillance, Epidemiology, 

and End Results; WHO = World Health Organization

With relatively small changes in the probability of presenting with symptoms, a model that 

allows 25 percent of Stage I tumors to progress directly to Stage III results in stage distributions 

similar to observed data, and results in similar lifetime risk of ovarian cancer as the Urban 

model,243 In a model with multiple input parameters, a huge number of combinations of 

parameters can result in similar outputs. Given that estimations of the duration of the different 

stages of ovarian cancer are based on little empirical data, and that there is no empirical data on 

the natural history of ovarian cancer, further exploration of the implications for screening, and 

the evaluation of masses detected through screening, is warranted. 

Summary 

The evidence is insufficient to develop a comprehensive model to estimate the relative 

benefits and risks of different management strategies for evaluating the adnexal mass. 

Based on summary estimates of pooled sensitivity and specificity, management strategies 

that use imaging as the first step for evaluating an adnexal mass detected on examination (as 

opposed to CA-125) are more efficient, since they exclude false positive results from further 

examination. Serial testing with imaging followed by CA-125 results in the fewest number of 
112

surgeries, but misses more cancers than parallel testing. Parallel testing greatly increases the 

number of tests required, but results in fewer missed cancers. Additional data are needed to 

evaluate cost-effectiveness. 

Alternative assumptions about the natural history of ovarian cancer can result in modeled 

outcomes similar to those of published models; the implications of these assumptions should be 

explored further. 
113

Chapter 4. Discussion 

Limitations of the Report 

There are several limitations to this evidence report: 

• We did not review articles published in languages other than English because of a lack of 

resources for translation. It is possible that this led to the failure to include some relevant 

articles. 

• For our review of prevalence studies (Question 1), we excluded studies performed 

outside the United States. Because the report was requested by the Centers for Disease 

Control and Prevention (CDC) to help with development of their policies and research 

agenda into ovarian cancer prevention strategies, we focused on U.S. populations and 

reasoned that the underlying prevalence of different conditions in women with adnexal 

masses could well differ in potentially important ways due to differences in racial/ethnic 

distribution and/or environmental exposures. As discussed in Chapter 2, this is supported 

by wide international variation in the incidence of cancer. Variations in screening, 

diagnosis, and surgical management could also lead to differences in the prevalence of 

various conditions among women with adnexal masses. It is possible that this reasoning 

was incorrect, and that some relevant articles were excluded. However, some non-U.S.-

based articles were reviewed for other questions, and the majority shared the same biases 

as U.S.-based studies (i.e., most were done immediately preoperatively). 

• There was considerable heterogeneity in design and patient populations among studies, 

and our use of a random-effects model to perform meta-analyses for some questions may 

have led to inaccurate estimates of pooled sensitivity and specificity. We also did not 

weight the results by anything other than sample size; it is possible that different results 

might have been obtained by weighting for study quality, for example. 

• In our review of data from the Nationwide Inpatient Sample, we used only specific 

International Classification of Diseases, Ninth Revision (ICD-9) “E” class codes to 

identify complications. A more exhaustive strategy (e.g., identifying procedures not 

typically performed at the time of diagnostic surgery, identifying blood transfusions 

through procedure or charge codes, including patients with cancer who underwent 

hysterectomy) might have revealed more complications,26 but would have required 

additional assumptions about the original indication for the surgery and the likely 

potential contribution of different aspects of the procedure to the complication (e.g., 

hysterectomy vs. oophorectomy). 

• Our exploration of alternative models for the natural history of ovarian cancer did not 

directly compare estimated outcomes of screening strategies to other models. However, a 

comprehensive evaluation of screening for ovarian cancer was beyond the scope of this 

report. We are currently developing the model further to conduct these analyses. 
114

Methodological Issues in the Literature 

Description of the Patient Population 

The main shortcoming of many of the papers reviewed was a failure to adequately describe 

the patient population, including the manner in which the adnexal mass was originally detected 

and subsequent evaluation. In Chapter 1, we described the importance of understanding the 

clinical presentation of the subjects in studies of management of adnexal masses. Because 

prevalence directly affects predictive values and may indirectly affect estimates of sensitivity and 

specificity, the probability that a patient is a true or false positive, or true or false negative, is 

dependent on the prevalence. In addition, the presence or absence of symptoms can affect the 

probability that a patient will undergo surgery if test findings indicate a benign mass, since 

surgery may still be the treatment of choice for the underlying condition. We were disappointed 

that the overwhelming majority of the studies we reviewed, relevant to all of the questions, did 

not adequately describe their population, so that the proportions of patients who presented with 

asymptomatic masses versus those with symptoms could be compared. 

To be fair, there is an inherent feasibility issue in studies of diagnostic test accuracy for 

ovarian cancer – the ideal reference standard is histological confirmation, yet this confirmation 

requires surgery. Although this is a limitation of all cancer screening tests, the surgery required 

for a definitive diagnosis of ovarian cancer is more extensive than that for many cancers (for 

example, cervical, breast, and colon cancer can all be diagnosed without a requirement for 

general anesthesia). Especially with screening, or early in the diagnostic evaluation, the risks of 

surgery may be difficult to justify (especially since the low prevalence of malignancy makes the 

positive predictive value of tests early in the diagnostic evaluation quite low). From a research 

ethics perspective, it is certainly reasonable to limit diagnostic test studies to patients already 

scheduled for surgery. However, readers of these studies should recognize that the prevalence of 

malignancy will be substantially higher in preoperative patients than in patients at the time of the 

initial diagnosis of adnexal mass. Because test performance may be affected by prevalence, the 

outcomes (in terms of true and false test results) may be quite different in these two patient 

populations. 

The same caveats hold for studies of the outcomes of surgery. Morbidity and mortality 

related to surgical diagnosis are influenced by the underlying diagnosis, as well as the extent of 

the disease (such as size of the mass, presence of adhesions from the disease process or prior 

unrelated surgery, or cancer stage). Interpreting surgical outcomes from studies that do not 

provide relevant clinical information is difficult; at the least, generalizablity is a major concern. 

Lack of relevant clinical information is a particular problem with administrative databases, 

which otherwise have the attraction of large sample size and better generalizability.26

An even more basic shortcoming was the failure to describe potential differences in study 

results stratified by age or menopausal status. Given the clear and widely recognized 

relationship between age and ovarian cancer risk, all studies in this area should present results in 

a way that allows separate estimation of outcome by age/menopausal status. 
115

Sample Size 

Few of the studies we reviewed included a priori sample size calculations. Use of confidence 

intervals for parameter estimates was uncommon. In studies of scoring systems, there were often 

too few cases of cancer for the number of variables included in the original models. 

Blinding 

Relatively few of the diagnostic studies reported whether those interpreting test results were 

blinded to either clinical presentation or ultimate diagnosis. This could clearly have an impact, 

particularly in studies of the bimanual pelvic examination; the finding that specificity decreased 

as prevalence increased suggests that the threshold for identifying a mass as cancer is lower if the 

clinical suspicion – based on other factors such as patient age, menopausal status, or history – is 

higher. Although this may be appropriate clinically, it results in biased estimates of test 

performance. 

Observer Variability 

Few studies addressed the potential impact of observer variability on the precision of test 

characteristics. 

Natural History of Ovarian Cancer 

As discussed in more detail in the section on Question 7, ovarian cancer has been implicitly 

assumed to progress through a series of stages in a way analogous to cervical cancer. Alternative 

models are biologically plausible, and mathematical models can be “fitted” to match reported 

data under a variety of scenarios. Since existing models already show that the effectiveness of 

screening is dependent on assumptions about the length of Stage I, further exploration of the 

impact of varying assumptions about natural history is warranted. 

The most important parameter in these models, stage duration, is inherently unknowable; 

however, the source for the parameter estimate in the two most sophisticated models were 

“personal communications” with two gynecologic oncologists. At the least, more formal 

methods of eliciting expert opinion are probably warranted for future modeling studies. 

Implications of Findings 

Question 1 

The prevalence of malignancy, even in postmenopausal women, is low – approximately 0.1 

percent (1 in 10,000) in large screening studies in the United States. The potential for screening 

to reduce morbidity and mortality is currently being tested in at least three large trials; these trials 

should also provide valuable data on disease prevalence and the effectiveness of various 

followup strategies. 
116

Question 2 

Until the results of the large screening trials are available, many, if not most, women with 

asymptomatic adnexal masses will have had the mass detected as part of a routine health 

maintenance examination. 

The bimanual pelvic examination appears to have a sensitivity of less than 60 percent, 

whether for detecting adnexal masses in general or for distinguishing benign from malignant 

masses. Based on the best pooled estimate of sensitivity (45 percent) and a prevalence of 0.1 

percent, a normal risk, asymptomatic, postmenopausal woman with a normal pelvic examination 

has a 99.94 percent chance of not having cancer, even though over half of the cancers would be 

missed. This is due to the low prevalence of ovarian cancer, since, even without the test, her 

probability of not having cancer is 99.99 percent. Given these test characteristics, the value of 

the pelvic examination in reducing ovarian cancer morbidity and mortality appears to be 

extremely limited, at best. Although there may be some rationales for an annual bimanual 

examination (discussed in Chapter 5), ovarian cancer screening is not one of them. 

Question 3 

Of the various diagnostic imaging modalities, either a combination of ultrasound morphology 

and Doppler velocimetry, or magnetic resonance imaging (MRI), had the best combination of 

sensitivity and specificity for distinguishing benign from malignant disease. If confirmed by 

direct comparison, cost-effectiveness might be the most important determinant of which would 

be the optimal diagnostic procedure. Because the specificity of cancer antigen 125 (CA-125) is 

high in postmenopausal women, it is helpful in ruling in disease. 

Question 4 

Additional validation of scoring systems in new populations is required before widespread 

adaptation can be recommended. 

Question 5 

The most effective and efficient method for following patients who have been classified as 

having a benign mass is unclear, although unilocular cysts less than 10 cm appear to have a very 

low risk of malignancy. 

Question 6 

The risks of diagnostic laparoscopy or laparotomy, particularly in asymptomatic women who 

ultimately prove to have a benign lesion, are unclear. Overall morbidity appears to be low in 

reported series, but these are subject to numerous biases, particularly regarding selection for 

laparoscopy. Two small randomized trials suggest higher short-term morbidity with laparotomy 

compared to laparoscopy, but differences between the two groups raise the possibility of 

confounding. 
117

Question 7 

Based on our pooled estimates of sensitivity and specificity, serial testing of postmenopausal 

women with an adnexal mass detected by pelvic examination with either ultrasound morphology 

plus Doppler imaging, or MRI (which had similar sensitivities and specificities), followed by 

CA-125, resulted in the most efficient combination of number of tests, missed cancers, and 

surgeries. Parallel testing and using a scoring system such as the Risk of Malignancy Index 

resulted in fewer missed cancers than serial testing, but more overall tests and more surgeries. 

Additional data are needed to refine these estimates, to include the morbidities of the tests and 

surgeries, and to perform cost-effectiveness analyses. Either combined strategy is preferable to 

using imaging alone or CA-125 alone. 

We cannot directly compare these results to the joint guidelines of the Society of 

Gynecologic Oncologists (SGO) and American College of Obstetricians and Gynecologists 

(ACOG) on which patient to refer to a gynecologic oncologist247 because the data were not 

available to replicate their findings. However, our results are consistent with the guidelines, 

which recommend a CA-125 level above 35 for postmenopausal women, the presence of ascites, 

or evidence of adnexal or distant metastasis. 

Alternative assumptions and parameter estimates can be used to generate predicted cancer 

incidences similar to those seen in published models of the natural history of ovarian cancer. In 

order to better estimate the potential impact of different strategies for ovarian cancer screening, 

and for managing masses detected through screening or presenting with symptoms, additional 

models that explore the implications for alternative natural history assumptions are needed. Data 

from ongoing screening trials may provide estimates of many of the currently unknown 

parameters. 

119

Chapter 5. Future Research 

This section outlines research priorities identified through the review, both in terms of 

fundamental gaps in knowledge and in addressing methodological issues of existing studies. 

Minimal Data Reporting 

Our ability to stratify results by relevant patient characteristics, or to compare the potential 

effect of patient characteristics on different results from different studies, was limited by the lack 

of information in most studies. We would suggest that future studies relevant to the diagnosis 

and management of adnexal masses provide data on, and present results stratified by, the 

following minimum characteristics: 

• Patient age and/or menopausal status 

• Patient body mass index 

• Patient race and ethnicity 

• Presence or absence of risk factors for ovarian cancer, particularly family history 

• Means by which the adnexal mass was initially diagnosed—pelvic examination or 

imaging 

• Reason for the initial examination which led to diagnosis of mass: symptoms referable to 

pelvic mass or ovarian cancer, examination for other symptoms, asymptomatic screening 

for ovarian cancer, or asymptomatic screening for other conditions 

Prevalence of Different Types of Adnexal Masses 

• Large scale screening trials will provide some data on the prevalence of different types of 

masses. 

• Administrative data from surgical procedures may provide crude estimates, but some 

important information (like stage and grade of cancer, or histologic subtype) will likely be 

missing. In addition, relevant clinical data on presence or absence of symptoms and the 

diagnostic pathway leading to diagnosis will likely be missing. The best resource for 

obtaining the necessary data would likely be a large health maintenance organization (HMO) 

or third-party payer, which would allow comparison of inpatient and outpatient records, and 

followup of patients after diagnosis. Medicare data would provide similar information for 

women 65 and older. 

• Separate reporting of the prevalence of different types of masses among women with and 

without symptoms would be helpful for clinical decisionmaking. 

Diagnostic Testing 

• Ideally, tests would be evaluated at the stage in the clinical pathway in which they are to be 

used. 
120

• Since this means that many women who have a negative test will not undergo the reference 

standard, careful attention should be paid to development of alternative reference standards, 

including definitions of appropriate length of followup. 

• More direct comparisons of alternative tests should be performed; existing studies are 

frequently underpowered to detect clinically meaningful differences, or to establish 

equivalence. Based on pooled analyses, either magnetic resonance imaging (MRI) or 

combined ultrasound evaluation of morphology and Doppler velocimetry have attractive 

sensitivity and specificity. Only two studies, with a total of 200 subjects, have directly 

compared these modalities in the same patient population.91,100 In both of these studies, MRI 

was less sensitive but more specific than combined morphology/Doppler. More precise 

comparative estimates should be obtained. 

• There is a paucity of studies on positron emission tomography (PET) compared to other 

imaging modalities. Given that the Centers for Medicaid and Medicare Services (CMS) is 

now reimbursing for PET scans done within the setting of a clinical trial, there is an excellent 

opportunity for high-quality studies which avoid the deficiencies outlined in this report. 

• Although discriminating between benign and malignant lesions is the highest priority in most 

clinical situations, estimates of the sensitivity and specificity of various imaging modalities 

for specific nonmalignant lesions (endometriomas, mature teratomas, etc.) would be helpful 

for developing comprehensive management strategies, particularly in conjunction with good 

data on prevalence in premenopausal women. We identified multiple articles relevant to this 

question during our search, which were excluded because they were not relevant to the main 

study questions. Although many of the methodological issues identified here would be issues 

with these studies, a systematic review of this literature would have value. 

• New tumor markers should continue to undergo evaluation as diagnostic tests as they are 

identified, using appropriate methodological standards. 

Scoring Systems 

• Validation studies in new populations are needed. 

• Attention should be paid to adequate sample size. 

Followup Studies 

• Additional studies, with clear definitions for “benign” lesions and clear protocols for 

followup, with documentation of loss to followup, are needed. Because by definition these 

types of studies will not have histological confirmation of all test results, estimates of test 

performance from such studies may have some bias. 

Adverse Outcomes of Surgery 

• As with studies of prevalence, both currently published studies (mostly case series) and 

administrative data have significant deficiencies. Case series would be improved by clearer 

description of the clinical pathway by which patients ended up undergoing surgery, as well as 
121

by providing relevant clinical data (such as body mass index, history of prior surgeries, and 

extent of disease). 

• Data on outcomes from a variety of settings, including community settings, are needed. 

• Again, as with studies of prevalence, data from sources able to provide both inpatient and 

outpatient data over time, such as HMOs, third-party payers, and Medicare, are likely to 

provide the best combination of sample size, generalizability, and clinical detail. 

Sensitivity and Specificity of the Pelvic Examination 

• The annual bimanual pelvic examination appears to have little, if any, benefit for reducing 

ovarian cancer morbidity and mortality in asymptomatic women. Given that many 

organizations now recommend less frequent cervical cancer screening in many women, that 

no screening test has ever been shown to reduce morbidity and mortality from endometrial 

cancer, and that other gynecological cancers are too rare to justify population-based 

screening, it would appear that annual bimanual pelvic exams do not have a substantial 

benefit in reducing mortality. Therefore, evidence on the benefits of the exam would be 

helpful for patients, clinicians, and policymakers. Possible research areas include: 

3⁄4 Many clinicians argue that the annual exam provides a “cue” for women to interact 

with a clinician and receive other preventive services. 

 Would women be less likely to see a health professional on a regular basis if 

they would not get a pelvic examination? 

 If the exam does provide a “cue” for some women, what is its effectiveness 

and cost-effectiveness compared to alternative methods of improving 

adherence to periodic health maintenance schedules? 

 Are there some women who do not regularly see a health professional because 

of embarrassment/fear/discomfort regarding a pelvic exam who would be 

more likely to see one if they could be assured they would not get an exam? 

3⁄4 Others have argued that, after long experience, women expect to receive a pelvic 

examination (and Pap test) on an annual basis and will continue to demand the 

examination, despite evidence that the test has little benefit, or does not need to be 

performed on an annual basis. 

 How have patients reacted to other changes or paradigm shifts in medicine? 

Can patient expectations be changed in the face of new evidence? Do patient 

responses differ between changes in which one intervention is replaced by 

another, versus changes in which an intervention is no longer performed at 

all? 

3⁄4 Although the pelvic examination does not appear to have significant benefit as a 

screening test, does it have more value as a diagnostic test? 

3⁄4 Assuming the pelvic examination does have value as a diagnostic test, is there a 

relationship between volume/experience and test accuracy, as suggested by two of the 

studies we reviewed? If so, can routine examinations in asymptomatic women be 

justified as a method for maintaining exam skills? 

3⁄4 If there is a relationship between volume and accuracy, what are the implications for 

the performance of diagnostic bimanual examinations by generalists (e.g., internists, 

pediatricians, family practitioners, generalist nurse practitioners) versus specialists 

(e.g., obstetrician/gynecologists, nurse-midwives, etc) 
122

Modeling the Outcomes of Different Screening Strategies 

• Our modeling of the likely outcomes of different screening strategies was limited by the 

quantity and quality of data available for key parameters. Because this limited direct 

comparison of different testing strategies, we were not able to do a comprehensive 

comparison. The lack of data on patient characteristics, particularly symptom status, also 

prevented extensive analysis of the effects of different strategies in different clinical 

scenarios. Improving the evidence base for the other questions considered in the evidence 

report will make a substantial improvement in the ability to meaningfully model outcomes. 

• Data on relevant patient preferences for different outcomes are needed. 

• Data on relevant cost parameters are needed for cost-effectiveness analysis. 

• Data on relative test reproducibility can help determine the effect of observer variability on 

effectiveness and cost-effectiveness. 

Modeling the Natural History of Ovarian Cancer 

• We identified only three models, one of which was an updated version of another. Having 

several groups working on simulation modeling, using different assumptions, software, 

model structure, etc., has proven quite helpful in the case of cervical cancer. Additional 

work should be strongly encouraged. 

• In particular, models should explore alternative disease natural history parameters, and the 

implications for various strategies, including screening and primary prevention. 
123

Chapter 6. Conclusions 

Developing an effective and efficient algorithm for the evaluation of any condition requires 

good evidence on the prevalence of the condition at the first diagnostic encounter, and the 

sensitivity and specificity of the potential diagnostic tests to be used. With this information, one 

can estimate the outcomes, in terms of true and false positive and negative results, of each test. 

Various combinations of tests can be compared, and, ideally, the consequences of each test’s 

results in terms of benefits, harms, and costs can be estimated. 

In the setting of an adnexal mass, the primary issue is discriminating benign from malignant 

masses; ideally, all women with an underlying ovarian malignancy would receive appropriate 

surgical management (perfect sensitivity), and no woman with an asymptomatic benign mass 

would undergo unnecessary surgery (perfect specificity). The optimal strategy may well differ 

based on whether or not the patient presents with symptoms, both because the prevalence of 

disease is likely to be higher in the patient with symptoms (making the positive predictive value 

higher and the negative predictive value lower), and because surgical management may 

ultimately be appropriate for a symptomatic patient, and some asymptomatic patients, even if the 

mass is benign. Age and/or menopausal status are also important considerations, primarily 

because ovarian cancer is rare prior to age 50, but also because some of the risks of surgery may 

increase with age. 

Unfortunately, the overwhelming majority of the literature we reviewed did not provide 

sufficient detail on these important patient characteristics to allow confident estimation of the 

outcomes of different diagnostic strategies, so that we are unable to conclude that any of the 

strategies achieve the aims of maximizing appropriate treatment and minimizing unnecessary 

surgery. Outside of studies that were explicitly designed to evaluate screening, few articles 

described whether patients were symptomatic or asymptomatic, or testing done prior to the 

diagnostic test being evaluated. Surprisingly few studies reported results separately for 

premenopausal and postmenopausal women. Future studies need to provide this information. 

All of the diagnostic tests and scoring systems we evaluated exhibited a trade-off between 

sensitivity and specificity – studies of a given test that reported higher sensitivity had lower 

specificity, and vice versa. In pooled analysis, either the combination of ultrasound morphology 

and Doppler blood flow, or magnetic resonance imaging (MRI), had the best combination of 

sensitivity and specificity. Simple modeling of series and parallel tests suggests that, in 

postmenopausal women, imaging using ultrasound morphology and Doppler blood flow, or MRI, 

followed by CA-125, is both more sensitive (misses fewer cancers) and more specific (avoids 

more surgery) than either test alone. A strategy in which both tests were performed and used in a 

scoring system, the Risk Malignancy Index, prevented additional cancers but with twice as many 

tests and more surgeries. More data on key parameters are needed to determine if, in certain 

settings, alternative combinations of tests, performed in parallel or series, might have better 

outcomes or be more efficient. 

Studies of surgical management suffered from the same limitations in terms of description of 

patient characteristics, making estimation of the risks of false positive diagnostic testing 

impossible. Similarly, administrative data that only includes discharge information do not 

provide important clinical information. 
124

The bimanual pelvic examination has low sensitivity for both detection of adnexal masses 

and discriminating benign from malignant masses, raising doubts about its utility as a screening 

test in asymptomatic women. 

Ultimately, evaluation of potential strategies for reducing morbidity and mortality from 

ovarian cancer may require use of simulation models, a technique that has proven helpful in 

evaluating prevention strategies for other cancers. Because the natural history of ovarian cancer 

is relatively unknown, testing of alternative models is critical. Although a few sophisticated 

models exist, development of additional models would be helpful, especially in the context of 

evaluating results from ongoing trials of screening. If any of these trials show a benefit from 

screening, then the need for better evidence on the diagnostic evaluation of adnexal masses will 

become even more critical. 
125

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List of Acronyms/Abbreviations 

2D Two-dimensional 

3D Three-dimensional 

ACOG American College of Obstetricians and Gynecologists 

ACR American College of Radiology 

AFP Alpha-fetoprotein 

AHRQ Agency for Healthcare Research and Quality 

AUC Area under the curve 

CA-125 Cancer antigen 125 

CDC Centers for Disease Control and Prevention 

CEA Carcinoembryonic antigen 

CI Confidence interval 

CMS Centers for Medicaid and Medicare Services 

CT Computed tomography 

FDG 18-Fluorodeoxyglucose 

FIGO International Federation of Gynecology and Obstetrics 

FNA Fine needle aspiration 

hCG Human chorionic gonadotropin 

ICD-9 International Classification of Diseases, Ninth Revision 

LDH Lactate dehydrogenase 

LMP Low malignant potential 

MeSH Medical Subject Heading 

MRI Magnetic resonance imaging 

NIS Nationwide Inpatient Sample 

NPV Negative predictive value 

PET Positron emission tomography 

PI Pulsatility index 

PPV Positive predictive value 

RI Resistance index 

RMI Risk of Malignancy Index 

ROC Receiver operating characteristic 

SEER Surveillance, Epidemiology, and End Results 

SGO Society of Gynecologic Oncologists 

TAG-72 Tumor-associated glycoprotein 72 

TVUS Transvaginal ultrasound 
APPENDIXES 

to 

“Management of Adnexal Mass” 

Prepared by the Duke Evidence-based Practice Center 

(Contract #290-02-0025) 
A-1

Appendix A: Exact Search Strings 

Search Strategy 1: pelvic exam performance 

(developed and run by McCrory and Myers on September 10, 2004) 

Database: Ovid MEDLINE(R) <1966 to September Week 1 2004> 

Search Strategy: 

-------------------------------------------------------------------------------- 

1 pelvic exam.mp.(53) 

2 (bimanual adj pelvic).mp. [mp=title, original title, abstract, name of substance, mesh 

subject heading] (25) 

3 (physical exam and pelvis).mp.(7) 

4 "diagnostic techniques, obstetrical and gynecological"/ or culdoscopy/ or laparoscopy/ 

or physical examination/ (45383) 

5 physical examination/ (18265) 

6 Ovarian Cysts/ or Ovarian Neoplasms/ or Genital Neoplasms, Female/ or Adnexal 

 Diseases/ or adnexal mass.mp. (48599) 

7 exp Ovarian Cysts/ or exp Ovarian Neoplasms/ or Genital Neoplasms, Female/ or 

 Adnexal Diseases/ or adnexal mass.mp. (53879) 

8 exp fallopian tube diseases/ (4449) 

9 5 and (7 or 8) (124) 

10 (or/1-3) and (or/7-8) (18) 

11 9 and 10 (5) 

12 "diagnostic techniques, obstetrical and gynecological"/ and (or/7-8) (8) 

13 culdoscopy/ and (or/7-8) (52) 

14 or/1-3,9-10 (204) 

15 limit 14 to (human and english language and yr=1980 - 2004) (147) 

16 from 15 keep 1-147 (147) 

*************************** 

Search Strategy 2: test performance 

Developed and run by McCrory on September 28, 2004 

Database: Ovid MEDLINE(R) <1966 to September Week 3 2004> 

Search Strategy: 

-------------------------------------------------------------------------------- 

1 (vagin$ adj ultraso$).mp. [mp=title, original title, abstract, name of substance, mesh 

subject heading] (1391) 

2 (adnex$ adj2 mas$).mp. (873) 

3 (pelvi$ adj mas$).mp. (1537) 

4 (ovar$ adj mas$).mp. (1479) 

5 or/2-4 (3696) 

6 "sensitivity and specificity"/ (121128) 

7 6 and 1 (132) 
A-2

8 6 and 5 (316) 

9 7 or 8 (431) 

10 limit 9 to (human and english language) (387) 

11 from 10 keep 1-387 (387) 

12 (ovar$ adj tumo$).mp. (11435) 

13 12 and 6 (405) 

14 ROC Curve/ (7282) 

15 13 and 14 (27) 

16 from 15 keep 4,7,9,15,19-20,22-23,27 (9) 

17 from 15 keep 22-23,27 (3) 

18 16 not 11 (4) 

19 11 or 18 (391) 

20 limit 19 to yr=1980 - 2004 (391) 

21 from 20 keep 1-391 (391) 

*************************** 

Search Strategy 3: predictive models 

(strategy developed and run by McCrory on September 29, 2004) 

Database: Ovid MEDLINE(R) <1966 to September Week 3 2004> 

Search Strategy: 

-------------------------------------------------------------------------------- 

1 (vagin$ adj ultraso$).mp. [mp=title, original title, abstract, name of substance, mesh 

subject heading] (1391) 

2 (adnex$ adj2 mas$).mp. (873) 

3 (pelvi$ adj mas$).mp. (1537) 

4 (ovar$ adj mas$).mp. (1479) 

5 or/2-4 (3696) 

6 "sensitivity and specificity"/ (121128) 

7 6 and 1 (132) 

8 6 and 5 (316) 

9 7 or 8 (431) 

10 limit 9 to (human and english language) (387) 

11 predictive value of tests/ (56850) 

12 Risk Assessment/ (47548) 

13 roc curve/ (7282) 

14 "Multivariate Analysis"/ (31714) 

15 or/11-14 (136223) 

16 15 and 5 (260) 

17 16 not 9 (142) 

18 limit 17 to (human and english language) (131) 

19 from 18 keep 1-131 (131) 

*************************** 
B-1

Appendix B: List of Excluded Studies 

All excluded studies listed below were reviewed in their full text version. Following each 

reference, in italics, is the reason(s) for exclusion and the Question (Q) for which the article was 

considered. If no Q is indicated, then the article was excluded a priori from the study for the 

reason given. An article can be considered (and therefore excluded) for more than one question, 

and all questions for which the article was excluded are identified. Reasons for exclusion signify 

only the usefulness of the articles for this study and are not intended as criticisms of the articles. 

For reference, the questions are: 

Question 1: What is the prevalence of various tumor types among women with an adnexal mass, 

stratified by cancer status (malignant vs. benign), age, menopausal status, and size of tumor? 

Question 2: What are the sensitivity, specificity, and reliability of the bimanual examination? 

Question 3: Among women with a palpable adnexal mass on exam or a mass identified by 

ultrasound/imaging, what is the sensitivity/specificity of various evaluation modalities including 

ultrasound (transvaginal ultrasound, transabdominal ultrasound, color Doppler, 2D vs. 3D 

ultrasound, CT scan, MRI scan, and CA-125 levels) for diagnosing malignant masses? 

Question 4: What is the accuracy of explicit scoring systems which incorporate various 

combinations of imaging findings, patient risk factors, and/or CA-125 levels for detecting 

malignancy? Have these scoring systems been applied to a population of women before 

laparoscopy? 

 

Question 5: Among women with suspected benign lesions on initial investigation, what are the 

sensitivity and specificity of monitoring with periodic CA-125 and/or interval ultrasound 

examinations for detecting malignant masses? How does the interval of testing/definition of 

change affect sensitivity and predictive value? 

Question 6: Among women with adnexal masses, what are the morbidity and mortality from 

diagnostic surgery (laparoscopy or laparotomy)? At what point does the risk of laparoscopy 

outweigh the risk of detecting malignancy? 

Question 7: What are the estimated trade-offs resulting from various strategies for evaluation of 

the adnexal mass? 

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tumor implantation after laparoscopic procedures in women 

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approach for the early detection of ovarian cancer in 

asymptomatic women. Eur J Obstet Gynecol Reprod Biol 

1996;65(2):221-5. Exclude Q5-wrong pt population.

Alcazar JL, Jurado M. Using a logistic model to predict 

malignancy of adnexal masses based on menopausal status, 

ultrasound morphology, and color Doppler findings. 

Gynecol Oncol 1998;69(2):146-50. Exclude Q3-unable to 

construct 2x2. 
B-2

Alcazar JL, Jurado M. Prospective evaluation of a logistic 

model based on sonographic morphologic and color 

Doppler findings developed to predict adnexal malignancy. 

J Ultrasound Med 1999;18(12):837-42. Exclude Q3-unable 

to construct 2x2. 

Alcazar JL, Laparte C, Jurado M, et al. The role of 

transvaginal ultrasonography combined with color velocity 

imaging and pulsed Doppler in the diagnosis of 

endometrioma. Fertil Steril 1997;67(3):487-91. Exclude 

Q1-sample size .

Alcazar JL, Ruiz-Perez ML, Errasti T. Transvaginal color 

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performs best? Ultrasound Obstet Gynecol 1996;8(2):114-

9. Exclude Q3-unable to construct 2x2.

Alexander-Sefre F, Menon U, Jacobs IJ. Ovarian cancer 

screening. Hosp Med 2002;63(4):210-3. Exclude review. 

Ali N, Jan H, Van Trappen P, et al. 

Radioimmunoscintigraphy with Tc-99m-labelled SM3 in 

differentiating malignant from benign adnexal masses. 

BJOG 2003;110(5):508-14. Exclude Q3-experimental or 

non-standard test.

Alvarez RD, Kilgore LC, Partridge EE, et al. Staging 

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rather than immediacy. South Med J 1993;86(11):1256-8. 

Exclude review. 

Alvarez-Sanchez F, Brache V, de Oca VM, et al. 

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levonorgestrel subdermal contraceptive implants 

(Norplant). Am J Obstet Gynecol 2000;182(3):535-9. 

Exclude Q3-no histol. dx.

American College of Obstetricians and Gynecologists. 

ACOG Committee Opinion: number 280, December 2002. 

The role of the generalist obstetrician-gynecologist in the 

early detection of ovarian cancer. Obstet Gynecol 

2002;100(6):1413-6. Exclude review.

Anderiesz C, Quinn MA. Screening for ovarian cancer. 

Med J Aust 2003;178(12):655-6. Exclude review.

Andersen WA, Nichols GE, Avery SR, et al. Cytologic 

diagnosis of ovarian tumors: factors influencing accuracy 

in previously undiagnosed cases. Am J Obstet Gynecol 

1995;173(2):457-63; discussion 463-4. Exclude Q3-wrong 

test.

Anderson MM, Irwin CE Jr, Snyder DL. Abnormal vaginal 

bleeding in adolescents. Pediatr Ann 1986;15(10):697-701. 

Exclude Q1-no histol. dx.

Andolf E, Jorgensen C, Astedt B. Ultrasound examination 

for detection of ovarian carcinoma in risk groups. Obstet 

Gynecol 1990;75(1):106-9. Exclude Q7-not descrip of sim 

model.

Angeid-Backman E, Coleman BG, Arger PH, et al. 

Comparison of resistive index versus pulsatility index in 

assessing the benign etiology of adnexal masses. Clin 

Imaging 1998;22(4):284-91. Exclude no mass.

Aslam N, Tailor A, Lawton F, et al. Prospective evaluation 

of three different models for the pre-operative diagnosis of 

ovarian cancer. BJOG 2000;107(11):1347-53. Exclude Q3-

inconsistent data. 

Aubel S, Wozney P, Edwards RP. MRI of female uterine 

and juxta-uterine masses: clinical application in 25 patients. 

Magn Reson Imaging 1991;9(4):485-91.Exclude Q3-

sample size.

Bandera CA, Ye B, Mok SC. New technologies for the 

identification of markers for early detection of ovarian 

cancer. Curr Opin Obstet Gynecol 2003;15(1):51-5. 

Exclude review. 

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B-11

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C-1

Appendix C: Sample Data Abstraction Forms

Question 1: What is the prevalence of various tumor types among peri- and postmenopausal women with an adnexal mass, stratified 

(malignant vs. benign), age, and size of tumor?Study Study Design Patients Clinical Presentation Results Comm

StudyID Geographical location: 

Dates:Size of population:[num/denom for screening studies] Screening study Registry Other [delete all but one; please specify “Other”] 

Age:Mean (SD): Median: Range: Menopausal status (n [%]):Pre (< 45): Peri (45-55): Post (> 55): Race/ethnicity (n [%]):

Risk factors (n [%]):Family history: Genotype: Other [specify]: 

Symptomatic (n [%]):Detected by exam (n [%]):Detected by imaging (n [%]):Combination (n [%]):Additional data used for diagnosis:

[Proportion of each type of finding, stratified by cancer status, age/menopausal status (<45, 45-55, >55 or pre-peri-postmenopausal), and size of tumor. Include individual tumor types where possible.] 

Use Excel spreadsheet to calculate confidence intervals for prevalence data from screening studies 1) 2) 3) 4) 5) 

[IF ARTEXCLUWHY H[COMMAFFECINTERPQuality [assign provide Size of sample NumbePatient ApplicaThis ar[delete QuestioQuestioQuestioQuestioQuestioQuestio
C-2

Question 2: What are the sensitivity, specificity, and reliability of the bimanual examination? 

Study Study Design Patients Clinical 

Presentation 

Clinical Setting of Exam 

Results 

StudyID Geographical 

location:Dates:Size of population:[num/denom for screening studies] Screening study Registry Other [delete all but one; please specify “Other”] Reference standard:

Reference standard applied to all test negatives?:

Test reliability established?:

Statistical tests used:

Blinding:

Definition of positive and negative on screening test:

Age:Mean (SD): Median: Range: Menopausal status (n [%]):Pre (< 45): Peri (45-55): Post (> 55): Race/ethnicity (n [%]):Risk factors (n [%]):

Family history: Genotype: Other [specify]: Inclusion criteria:Exclusion criteria:

Symptomatic (n [%]):Detected by exam (n [%]):

Detected by imaging (n [%]):Combination (n [%]):Additional data used for diagnosis:

[Please provide brief description of clinical setting in which bimanual exam was performed] 

[For bimanual exam, provide reported sensitivity/specificity and provide 2x2 tables (if possible). If possible and appropriate, stratify by age or menopausal status. If data are available on reliability/ reproducibility, report these as well. Include kappa scores if these are reported or can be calculated.] 1) [Use this space to provide information needed for reader to interpret Test +, Test -, Disease +, and Disease - headings in following table.] 

2) 
C-3

Question 3: Among peri- and postmenopausal women with a palpable adnexal mass on exam or a mass identified by ultrasound/imag

sensitivity/specificity of various evaluation modalities including ultrasound (transvaginal ultrasound, transabdominal ultrasound, color Dop

ultrasound, CT scan, MRI scan, and CA-125 levels) for diagnosing malignant masses?Study Study Design Patients Clinical Presentation Results Comm

StudyID Geographical location: 

Dates:Size of population:[num/denom for screening studies] Screening study Registry Other [delete all but one; please specify “Other”] Reference standard:

Reference standard applied to all test negatives?:

Test reliability established?:

Statistical tests used:

Blinding:Definition of positive and negative on screening test:

Age:Mean (SD): Median: Range: Menopausal status (n [%]):Pre (< 45): Peri (45-55): Post (> 55): Race/ethnicity (n [%]):Risk factors (n [%]):Family history: Genotype: Other [specify]: Inclusion criteria:Exclusion criteria:

Symptomatic (n [%]):Detected by exam (n [%]):Detected by imaging (n [%]):Combination (n [%]):

Additional data used for diagnosis:

[For each test reported, please provide a 2x2 table and report or calculate sensitivity, specificity, NPV, and PPV (all with confidence intervals). If possible and appropriate, stratify by age or menopausal status.] 1) [Use this space to provide information needed for reader to interpret Test +, Test -, Disease +, and Disease - headings in following table.] 

2) 

[IF ARTEXCLUWHY H[COMMAFFECINTERPQuality [assign provide ReferenVerificaTest reSample StatisticBlindingDefinitioThis ar[delete QuestioQuestioQuestioQuestioQuestioQuestio
C-4

Question 4: What is the accuracy of explicit scoring systems which incorporate various combinations of imaging findings, patient risk 

levels for detecting malignancy? Have these scoring systems been applied to a population of peri-/postmenopausal women before lapar

Study Study Design Patients Clinical 

Presentation 

Items Included in Scoring System 

Results 

StudyID Geographical 

location:Dates:Size of population:[num/denom for screening studies] Screening study Registry Other [delete all but one; please specify “Other”] Reference standard:

Reference standard applied to all test negatives?:

Statistical tests used:

Blinding:

Definition of positive and negative on screening test:

Age:Mean (SD): Median: Range: Menopausal status (n [%]):Pre (< 45): Peri (45-55): Post (> 55): Race/ethnicity (n [%]):Risk factors (n [%]):

Family history: Genotype: Other [specify]: Inclusion criteria:Exclusion criteria:

Symptomatic (n [%]):Detected by exam (n [%]):Detected by imaging (n [%]):Combination (n [%]):

Additional data used for diagnosis:

1) 2) 3) 4) 5) 6) 7) 8) 9) 10) 

[For each reported scoring system (and individual components, if reported), provide reported sensitivity/specificity and provide 2x2 table; if multivariate analysis, provide area under ROC curve or c-statistic, if reported. If possible and appropriate, stratify by age or menopausal status.] 1) [Use this space to provide information needed for reader to interpret Test +, Test -, Disease +, and Disease - headings in following table.] 

2) 
C-5

Study Study Design Patients Clinical 

Presentation 

Items Included in Scoring System 

Results 

Results were reported, but have not been abstracted, for the following combinations: [list] 

Question 5: Among women with suspected benign lesions on initial investigation, what is the sensitivity and specificity of monitoring w

interval ultrasound examinations for detecting malignant masses? How does the interval of testing/definition of change affect sensitivity 

Study Study Design Patients Clinical 

Presentation 

Monitoring Strategy Results Co

Sc

StudyID Geographical 

location:Dates:Size of population:[num/denom for screening studies] Screening study Registry Other [delete all but one; please specify “Other”] Reference standard:

Reference standard applied to all test negatives?:

Test reliability established?:

Statistical tests used:

Age:Mean (SD): Median: Range: Menopausal status (n [%]):Pre (< 45): Peri (45-55): Post (> 55): Race/ethnicity (n [%]):Risk factors (n [%]):Family history: Genotype: Other [specify]: Inclusion criteria:Exclusion criteria:Loss to follow up:

Symptomatic (n [%]):Detected by exam (n [%]):Detected by imaging (n [%]):

Combination (n [%]):Additional data used for diagnosis:

Monitoring test:Interval of testing:Definition of change:

[For each reported monitoring strategy, provide reported sensitivity/specificity and provide 2x2 table; if multivariate analysis, provide area under ROC curve or c-statistic, if reported. If possible and appropriate, stratify by age or menopausal status.] 1) [Use this space to provide information needed for reader to interpret Test +, Test -, Disease +, and Disease - headings in following table.] 

2) 

[IF EXEX[CAFINQu[asprReVeTeSaStBlDetesExThto
C-6

Study Study Design Patients Clinical 

Presentation 

Monitoring Strategy Results Co

Sc

Blinding:Definition of positive and negative on screening test:Length of follow up: 

Type of follow up:Follow-up interval:

3) 

QuQuQuQuQuQu
C-7

Question 6: Among women with adnexal masses, what is the morbidity and mortality from diagnostic laparoscopy? At what point doe

outweigh the risk of detecting malignancy? Study Study Design Patients Clinical Presentation Results Comm

StudyID Geographical location: 

Dates:Size of population:[num/denom for screening studies] Single center Registry [delete one] Morbidity definitions:

Length of follow up after surgery:

Age:Mean (SD): Median: Range: Menopausal status (n [%]):Pre (< 45): Peri (45-55): Post (> 55): Race/ethnicity (n [%]):Risk factors (n [%]):Family history: Genotype: Other [specify]: Loss to follow up:

Symptomatic (n [%]):Detected by exam (n [%]):Detected by imaging (n [%]):Combination (n [%]):Additional data used for diagnosis:

[For each, provide reported rate and 95% CI, if appropriate. If possible and appropriate, stratify results by age or menopausal status.] 

Use Excel spreadsheet to calculate confidence intervals for morbidity/mortality 1) Mortality: 2) Morbidity (total all complications): 3) Specific complications: 4) Rate of conversion to laparotomy: 5) 6) 

[IF ARTEXCLUWHY H[COMMAFFECINTERPQuality [assign provide Size of sample NumbePatient ApplicaThis ar[delete QuestioQuestioQuestioQuestioQuestioQuestio
C-8

Question 7: What are the estimated trade-offs resulting from various strategies for evaluation of the adnexal mass? 

Study Study Design Study Outcomes Sources for Model 

Probabilities 

Sources for Model Outcomes 

Results Co

StudyID Type of model:

Population modeled (age, range):Strategies compared: 

[Life expectancy, quality of life, cancer incidence, cancer death, etc. Include costs, but we will not be using them here] 

[In particular, sources for transition probabilities between different stages of precancer/cancer] Simplifying assumptions: 

[For each strategy compared, compare results for different outcomes; also, report results of significant sensitivity analyses.] 1) 2) 3) 

4) 5) 6) 

[IF EXW[CAFINTh[deQuQuQuQuQuQu
D-1 

Appendix D: Evidence Tables Evidence Table 1: Question 1: What is the prevalence of various tumor types among women with an adnexal mass, stratified by can

benign), age, menopausal status, and size of tumor?Study Study Design Patients Clinical Presentation Results Comm

Chalas, Welshinger, Engellener, et al., 1992 #5100 

Geographical location: Stony Brook, NY Dates: 

May 1980-Apr 1990 Size of population: 241 Other: Retrospective chart review of patients with pelvic mass who underwent laparotomy to look at thrombocytosis as a predictor of cancer 

Age: NR Menopausal status (n [%]): NR; authors present some findings by age > 50, but do not report the numbers of womenRace/ethnicity (n [%]): NR Risk factors (n [%]): NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: CA-125 and thrombocytosis 

Of the 241: 121/241 were malignant = 50.2%; 95% CI, 44.4 to 56.9 18/241 borderline = 7.5%; 4.8 to 11.7 102/241 benign = 42.3%; 36.6 to 49 Malignant: Serous epithelial 66 = 27.4%; 95% CI, 22.4 to 33.6 Mucinous epithelial 12 = 5.0%; 2.8 to 8.7 Clear cell epithelial 13 = 5.4%; 3.2 to 9.2 Endometrioid epithelial 11 = 4.6%; 2.5 to 8.2Papillary mixed epithelial 5 = 2.1%; 0.8 to 5.0 Dysgerminoma 2 = 0.8%; 0.05 to 3.2 Immature teratoma 1 = 0.4%; 0 to 2.6 Endodermal tumor 1 = 0.4%; 0 to 2.6 Granulose cell tumor 1 = 0.4%; 0 to 2.6 Sertoli-Leydig cell tumor 2 = 0.8%; 0.05 to 3.2 Peritoneal primary 1 = 0.4%; 0 to 2.6 Malignant mesothelioma 1 = 0.4%; 0 to 2.6 Other cancer 5 = 2.1%; 0.8 to 5.0 Borderline tumors (LMP): Serous epithelial 9 = 3.7%; 95% CI, 1.9 to 7.1 Mucinous epithelial 7 = 2.9%; 1.3 to 6.1 Endometrioid epithelial 1 = 0.4%; 0 to 2.6 Papillary mixed epithelial 1 = 0.4%; 0 to 2.6 Benign: Functional ovarian cyst 22 = 9.1%; 95% CI, 6.1 to 13.6 Serous cystadenoma 14 = 5.8%; 3.5 to 9.7 Mucinous cystadenoma 9 = 3.7%; 1.9 to 7.1Brenner tumor 1 = 0.4%; 0 to 2.6 Endometrioma 10 = 4.1%; 2.2 to 7.6 Mature teratoma 6 = 2.5%; 1.1 to 5.5 Thecoma of fibroma 4 = 1.7%; 0.5 to 4.4 Tuboovarian abscess 4 = 1.7%; 0.5 to 4.4 

Comme--Clinica--PatienmalignaQuality Size of sample NumbePatient chart reApplica(all had 
D-2

Evidence Table 1 (continued) 

Study Study Design Patients Clinical Presentation Results Comm

Hydrosalpinx 4 = 1.7%; 0.5 to 4.4 Paratubal cyst 1 = 0.4%; 0 to 2.6 Leiomyoma 22 = 9.1%; 6.1 to 13.6Pseudomyxoma 2 = 0.8%; 0.05 to 3.2 Endometriosis 1 = 0.4%; 0 to 2.6 Mesothelial cyst 1 = 0.4%; 0 to 2.6 Diverticular abscess 1 = 0.4%; 0 to 2.6 

Childers, Nasseri, and Surwit, 1996 #6940 

Geographical location: Tucson, AZ Dates: 

1991-1995 Size of population: 138 Other 138 with adnexal mass 

Age: Mean: 52 Range: 9-91 Menopausal status (n [%]): NRRace/ethnicity (n [%]): NR Risk factors (n [%]): NR

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: All subjects had some concerning finding: CA-125 elevated: 39 (28%) Abnormal US: 127 (92%) Mass > 10 cm: 43 (32%) 

Benign: 119/138 (86.2%; 95% CI, 80.8 to 92.1) 23 (16.7%; 11.6 to 24.2) cystadenoma 9 (6.5%) 3.4 to 12.3) mucinous cystadenoma 9 (6.5%; 3.4 to 12.3) cystadenofriboma 11 (8.0%; 4.5 to 14.1) benign teratoma 21 (15.2%; 10.3 to 22.5) endometrioma 2 (1.4%; 0.1 to 5.6) Brenner cell 1 (0.7%; 0 to 4.5) struma ovarii 9 (6.5%; 3.4 to 12.3) hydrosalpinx 3 (2.2%; 0.5 to 6.6) corpus luteum 6 (4.3%; 1.9 to 9.5) paraovarian cyst 15 (10.9%; 6.8 to 17.5) leiomyoma 6 (4.3%; 1.9 to 9.5) ovarian fibroma 3 (2.2%; 0.5 to 6.6) chronic tuboovarian abscess Malignant: 19/138 (13.8%; 95% CI, 9.1 to 20.9) (16 of 19 adnexal primaries) 5 (3.6%; 1.4 to 8.6) serous carcinoma 5 (3.6%; 1.4 to 8.6) serous cystadenocarcinoma 6 (4.3%; 1.9 to 9.5) endometroid carcinoma 3 (2.2%; 0.5 to 6.6) mixed endometroid and serous carcinoma Stage 1= 6 Stage 2 = 2 Stage 3 = 5 Unstaged = 3 (assumed to be Stage I), but 2 had recurrence 

Comme--Patienprevale-ClinicaQuality Size of sample hospitaNumbePatient Applica(all had 
D-3

Evidence Table 1 (continued) 

Study Study Design Patients Clinical Presentation Results Comm

Cohen, Escobar, Scharm, et al., 2001 #2460 

Geographical location: Chicago, IL Dates: 

Apr 1999-Jun 2000 Size of population: 71 Other Women with a complex pelvic mass undergoing laparotomy 

Age: Range: 22-80 Menopausal status (n [%]): Pre (< 45): 40 (56%) Post (> 55): 31 (44%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

Malignant: 13/71 = 18.3%; 95% CI, 11.4 to 29.7 Serous cystadenocarcinoma 5 = 7%; 2.9 to 16.2 Mucinous cystadenocarcinoma 1 = 1.4%; 0 to 8.6 Clear cell adenocarcinoma 1 = 1.4%; 0 to 8.6 Mixed mullerian 1 = 1.4%; 0 to 8.6 Malignant germ cell tumor 2 = 2.8%; 0.3 to 10.6 Metastatic sarcoma 1 = 1.4%; 0 to 8.6 Metastatic colon 2 = 2.8%; 0.3 to 10.6 Borderline tumors (LMP): 1/71 = 1.4%; 0 to 8.6 Serous cystadenocarcinoma 1 = 1.4%; 0 to 8.6 Benign: 57/71 = 80.3%; 71.9 to 89.7 Serous cystadenoma 9 = 12.7%; 7.0 to 23.2Mucinous cystadenoma 6 = 8.4%; 3.9 to 18.0 Adenofibroma 10 = 14.1%; 8 to 24.8 Endometrioma 11 = 15.5%; 9.1 to 26.5 Cystic teratoma 13 = 18.3%; 11.4 to 29.7 Thecoma 1 = 1.4%; 0 to 8.6 Hydrosalpinx 4 = 5.6%; 2 to 14.4 Tamoxifen stimulation 2 = 2.8%; 0.3 to 10.6 Leiomyoma 1 = 1.4%; 0 to 8.6 

Comme--8/13 amalignawomen --Clinica--PatienmalignaoverrepQuality Size of sample NumbePatient adnexaApplica(all had 

DePriest, Geographical location: Age: Symptomatic (n [%]): Of the 6470 screened: Comme
D-4

Evidence Table 1 (continued) 

Study Study Design Patients Clinical Presentation Results Comm

Gallion, Pavlik, et al., 1997 #3650 

Lexington, KY Dates: 

Dec 1987-Dec 1993 Size of population: 6470; 8 found to have cancer (7 of these cancers were ovarian) Screening study Used TVUS in asymptomatic women > 50 or postmenopausal and women > 30 with positive family history of ovarian carcinoma 

Mean: 58 Range: 30-92 Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): Family history of: Ovarian cancer: 24% Breast cancer: 30% Colon cancer: 15% 

NR Detected by exam (n [%]): NR Detected by imaging (n [%]): 99% (all but one was detected by imaging) Combination (n [%]): NR Additional data used for diagnosis: NR 

7/6,470 malignant (ovarian) = 0.11%; 95% CI, 0.05 to 0.2 1/6,470 malignant (non-ovarian) = 0.02%; 0 to 0.1 83/6,470 benign = 1.2%; 1.0 to 0.12 Malignant: Granulosa cell tumor 3 = 0.05%; 95% CI, 0.01 to 0.14 Adenocarcinoma 2 = 0.03%; 0 to 0.12 Serous cystadenocarcinoma 1 = 0.02%; 0 to 0.1 Endometrioid carcinoma 1 = 0.02%; 0 to 0.1Metastatic colon cancer 1 = 0.02%; 0 to 0.1 Benign: Serous cystadenoma 37 = 0.6%; 95% CI, 0.4 to 0.8 Endometriosis 18 = 0.3%; 0.2 to 0.4 Mucinous cystadenoma 3 = 0.05%; 0.01 to 0.14 Cystic teratoma 3 = 0.05%; 0.01 to 0.14 Hemorrhagic cyst 2 = 0.03%; 0 to 0.12 Fibroma/thecoma/Brenner tumor 4 = 0.06%; 0.02 to 0.2 Leiomyomata 4 = 0.06%; 0.02 to 0.2 Hydrosalpinx/paratubal 8 = 0.12%; 0.06 to 0.25 Other 4 = 0.06%; 0.02 to 0.2 

--Overlastudy p(DePrieal., 199--Most breast oQuality Size of sample NumbePatient mix of phigh-risApplica(all had 

DePriest, Shenson, 

Geographical location: Lexington , KY 

Age: Range: 3-74 

Symptomatic (n [%]): NR 

Malignant: 13/121 = 10.7%; 95% CI, 6.5 to 17.9 

Comme--Clinica
D-5

Evidence Table 1 (continued) 

Study Study Design Patients Clinical Presentation Results Comm

Fried, et al., 1993 #6390 

Dates: 

Jan 1987-Jan1992 Size of population: 121 Other Women with ovarian mass undergoing laparotomy 

Menopausal status (n [%]): Pre (< 45): 62 (51%) Post (> 55): 59 (49%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR 

Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

Serous cystadenocarcinoma 6 = 5%; 2.2 to 10.8 Mucinous cystadenocarcinoma 2 = 1.6%; 0.1 to 6.4 Granulosa cell tumor 1 = 0.8%; 0 to 5.1 Metastatic adenocarcinoma 2 = 1.6%; 0.1 to 6.4 Neurogenic sarcoma 1 = 0.8%; 0 to 5.1 Lymphoma 1 = 0.8%; 0 to 5.1 Benign: 108/121 = 89.3%; 95% CI, 84 to 94.8 Serous cystadenoma 21 = 17.4%; 11.9 to 25.5 Mucinous cystadenoma 2 = 1.6%; 0.1 to 6.4PID 18 = 14.9%; 9.8 to 22.7 Benign cysts = 17 = 14%; 9.1 to 21.8 Endometriosis 14 = 11.6%; 7.1 to 18.9 Hemorrhagic corpus luteum cyst 12 = 9.9%; 5.8 to 16.9 Teratoma 11 = 9.1%; 5.2 to 16 Fibroma = 5 = 4.1%; 1.6 to 9.7 Leiomyoma 4 = 3.3%; 1.1 to 8.6 Normal ovary 4 = 3.3%; 1.1 to 8.6 

--PatienmalignaQuality Size of sample NumbePatient to surgeApplica(all had 

DePriest, van Nagell Jr., Gallion, 

Geographical location: Lexington, KY 

Age: Mean: 60 Range: 33-90 

Symptomatic (n [%]): 0 

Benign: 41/3220 (1.3%; 95% CI, 0.9 to 1.7) 21 (0.7%; 0.4 to 1.0) serous cystadenoma 

Comme--Majoreither b
D-6

Evidence Table 1 (continued) 

Study Study Design Patients Clinical Presentation Results Comm

et al., 1993 #6880 

Dates: 

Nov 1987-Jun 1992 Size of population: 3220 3 had cancer Screening study (and most had a positive family history)

Menopausal status (n [%]): Post (> 55): 100% Race/ethnicity (n [%]): NR Risk factors (n [%]): Family history of: Ovarian cancer: 502 (15.6%) Breast cancer: 1034 (32.1%) Colorectal cancer: 678 (21.1%) 

Detected by exam (n [%]): 0 Detected by imaging (n [%]): 44 had abnormal TVUS (1.4%) Combination (n [%]): 0 Additional data used for diagnosis: NR 

4 (0.1%; 0.04 to 0.30) endometrioma 1 (0.03%; 0.0.2) cystadenofibroma 1(0.03%; 0.0.2) thecoma 1 (0.03%; 0.0.2) teratoma 2 (0.06%; 0 to 0.2) fibroma 3 (0.09%; 0.02 to 0.3) hydrodsalpinx 5 (0.16%; 0.06 to 0.4) paratubal cyst 3 (0.09%; 0.02 to 0.3) myoma Malignant: 3/3220 (0.09%; 95% CI, 0.02, 0.29%) 3 primary ovarian adenocarcinoma 2 Stage IA 1 Stage IIIB 

cancer --True nbiopsy within 1 Quality Size of sample represeNumbewith caPatient history) Applica(explora

Dottino, Levine, Ripley, et al., 1999 #6920 

Geographical location: New York, NY Dates: 

Apr 1992-Apr 1996 Size of population: 160 OtherAdnexal mass undergoing laparoscopic surgery 

Age: Mean (SD): 52.2 (13.1) Menopausal status (n [%]): Pre (< 45): 75 (47%) Post (> 55): 85 (53%) Race/ethnicity (n [%]): White 146 (91%) Risk factors (n [%]): NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

Benign: 139/160 (86.9%; 95% CI, 81.9 to 92.2) Borderline: 8 (5%; 95% CI, 2.5 to 9.9) Malignant: 13 (8.1%; 95% CI, 4.8 to 13.7) 6 epithelial cancers (3.7%; 1.6 to 8.2)  2 Stage 1A (1.2%; 0.09 to 4.8)  1 Stage 2C (0.6%; 0 to 3.9)  1 Stage 3A (0.6%; 0 to 3.9)  1 Stage 3C (0.6%; 0 to 3.9)  1 Stage 4 (0.6%; 0 to 3.9) 3 sex cord stromal tumors (1.9%; 0.4 to 5.7)  2 Sertoli-Leydig cell (1.2%; 0.09 to 4.8)  1 granulosa cell (0.6%; 0 to 3.9) 4 non-gynecologic cancers (4%; 0.8 to 6.6) 

Comme--ClinicaQuality Size of sample NumbePatient Applica(all had 

Fleischer, Cullinan, Jones 3rd, et 

Geographical location: Nashville, TN 

Age: Mean: 50 Range: 17-88 

Symptomatic (n [%]): NR 

Benign: 31/62 (50%; 95% CI, 39.5 to 63.5)10 (16.1%; 9.3 to 28.2) hemorrhagic corpus luteum 

Comme--Clinica
D-7

Evidence Table 1 (continued) 

Study Study Design Patients Clinical Presentation Results Comm

al., 1996 #3840 

Dates: 

1990-1995 Size of population: 62 OtherPatients who underwent Doppler for adnexal mass

Menopausal status (n [%]): Pre (< 45): NR Peri (45-55): NR Post (> 55): (over 50%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR

Detected by exam (n [%]): NR Detected by imaging (n [%]): 100% Combination (n [%]): NR Additional data used for diagnosis: NR 

1 (1.6%; 0 to 9.8) serous cyst 4 (6.4%; 2.3 to 16.4) cystadenomas 4 (6.4%; 2.3 to 16.4) endometriomas 8 (12.9%; 6.9 to 24.4) dermoid cysts 2 (3.2%; 0.4 to 12.1) ovarian fibroma 2 (3.2%; 0.4 to 12.1 leiomyoma Malignant: 31/62 (50%; 95% CI, 39.5 to 63.5) 16 (25.8%; 17.3 to 39.0) cystadenocarcinomas 1 (1.6%; 0 to 9.8) papillary serous adenocarcinomas 1 (1.6%; 0 to 9.8) endometroid carcinoma 1 (1.6%; 0 to 9.8) dysgerminoma 4 (6.4%; 2.3 to 16.4) metastases 4 (6.4%; 2.3 to 16.4) germ cell tumors 4 (6.4%; 2.3 to 16.4) stromal tumors 

Quality Size of sample NumbeCIs) Patient Applica(all had 

Lin, Angel, DuBeshter, et al., 1993 #4890 

Geographical location: Rochester NY Dates: 

Jun 1989-Jun 1990 Size of population: 80 OtherPelvic masses undergoing laparoscopic surgery 

Age: Median: 56 Range: 19-88 Menopausal status (n [%]): Pre (< 45): NR Peri/Post: 62 (76%) Race/ethnicity (n [%]): White 72 (90%) Black 8 (10%) Risk factors (n [%]): Family history of: Ovarian/breast/colon cancer: 11 (14%) 

Symptomatic (n [%]): 70 (87%) Detected by exam (n [%]): 80 (100%) --59 (74%) with discrete mass --21 (26%) ill-defined fullnessDetected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

Benign: 32/80 (40%; 95% CI, 30.9 to 52) 23 (28.7%; 20.6 to 40.3) benign cyst 8 (10%; 5.2 to 19.2) other benign gynecologic condition 1 (1.2%; 0 to 7.7) diverticular disease Borderline: 2/80 (2.5%; 95% CI, 0.3 to 9.5)Malignant: 46/80 (57.5%; 48 to 69.1) 6 (7.5%; 3.4 to 16.1) colorectal carcinoma 1 (1.2%; 0 to 7.7) endometrial carcinoma 1 (1.2%; 0 to 7.7) vaginal carcinoma 2 (2.5%; 0.3 to 9.5) breast carcinoma 2 (2.5%; 0.3 to 9.5) lymphoma 4 (5%; 1.7 to 12.9) multiple sites 30 (37.5%; 28.6 to 49.5) ovarian carcinoma  6 (7.5%; 3.4 to 16.1) Stage 1  26 (32.5%; 24 to 44.3) Stage 3  4 (5%; 1.7 to 12.9) Stage 4 

Comme--ClinicaQuality Size of sample NumbePatient Applica(all had 

Modesitt, Pavlik, Ueland, et 

Geographical location: Lexington, KY 

Age: Range: 50-70+ 

Symptomatic (n [%]): 0 

Benign: 117/15106 (0.8%; 95% CI, 0.6 to 0.9) 61 (0.4%; 0.3 to 0.5) serous cystadenomas 

Comme--Althouare help
D-8

Evidence Table 1 (continued) 

Study Study Design Patients Clinical Presentation Results Comm

al., 2003 #5560 

Dates: 

1987-2002 Size of population: 27 cancers/15,106 Screening study with TVUS and followed up with Doppler and CA125 if abnormal

Menopausal status (n [%]): Post (> 55): 100% Race/ethnicity (n [%]): NR Risk factors (n [%]): Family history: some but NR 

Detected by exam (n [%]): 0 Detected by imaging (n [%]): 100% Combination (n [%]): NR Additional data used for diagnosis: NR 

14 (0.09%; 0.05 to 0.16) serous cystadenofibromas 9 (0.06%; 0.03 to 0.12) mucinous cystadenoma 9 (0.06%; 0.03 to 0.12) paraovarian 7 (0.05%; 0.02 to 0.1) fibrothecoma 5 (0.03%; 0.01 to 0.08) endometrioma 3 (0.02%; 0 to 0.06) cystic teratoma 1 (0.01%; 0 to 0.04) mucinous cystadenofibroma 8 (0.05%; 0.03 to 0.11) other Malignant: 27/15106 (0.18%; 95% CI, 0.12 to 0.26) 17 (0.11%; 0.07 to 0.18) Stage 1 4 (0.03%; 0.01 to 0.07) Stage 2 6 (0.04%; 0.02 to 0.09) Stage 3 Note: this is a separate group; of these 27, 10 had had simple ovarian cyst at one point in screening; 7 had additional morphologic abnormality, 2 had resolution of cyst before developing cancer, 1 had cancer in contralateral ovary Unilocular cyst – cumulative incidence by age: 50-54 1315/5229 (25.1%) 55-59 481/3278 (14.7%) 60-64 373/2694 (13.8%) 65-69 271/2008 (13.5%) 70+ 323/1897 (17.0%) 

annual provideQuality Size of sample NumbePatient all over Applica(subset 

Parker, Levine, Howard, et al., 1994 

Geographical location: Santa Monica, Irvine, and Los Angeles, CA; Louisville, KY; 

Age: Mean: 65 Range: 47-81 

Symptomatic (n [%]): NR Detected by exam (n [%]): 

All tumors were benign and were in postmenopausal women: 27 (44.3%; 95% CI, 33.9 to 58.1) serous cystomas 

Comme--ClinicaQuality 
D-9

Evidence Table 1 (continued) 

Study Study Design Patients Clinical Presentation Results Comm

#910 

Rochester, NY Dates: 

NR; published 1994 Size of population: 61 OtherLaparoscopic management of benignappearing cystic masses 

Menopausal status (n [%]): Post (> 55): 61 (100%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR 

NR Detected by imaging (n [%]): 100% Combination (n [%]): NR Additional data used for diagnosis: NR 

15 (24.6%; 16.2 to 37.8) serous cystadenomas 1 (1.6%; 0 to 9.9) mucinous cystadenomas 5 (8.2%; 3.5 to 18.7) cystadenofibromas 4 (6.6%; 2.4 to 16.7) hydrosalpinges 6 (9.8%; 4.6 to 20.8) paratubal cysts 3 (4.9%; 1.4 to 14.5) paraovarian cysts 

Size of sample Numbewide CIPatient benign-Applica(all had 

Roman, Muderspach, Stein, et al., 1997 #6160 

Geographical location: Los Angeles, CA Dates: 

Jul 1992-Mar 1994 Size of population: 226 Other: Prospective study of women scheduled for removal of pelvic mass; included women with pregnancy

Age: NR Menopausal status (n [%]): Pre (< 45): 181 (80%) Post (> 55): 45 (20%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

Of the 226 enrolled: 26/226 were malignant = 11.5%; 95% CI, 8.0 to 16.5 17/226 borderline tumors = 7.5%; 4.8 to 11.9 183/226 were benign = 81%; 76.1 to 86.2 Malignant: Epithelial cancer 15 = 6.6%; 95% CI, 4.1 to 10.9 Germ cell cancer 4 = 1.8%; 0.6 to 4.7 Stromal cancer 6 = 2.7%; 1.1 to 5.9 Sarcoma 1 = 0.4%; 0 to 2.8 Borderline tumors: LMP 17 = 7.5%; 95% CI, 4.8 to 11.9 Benign: Simple or functional cyst 46 = 20.4%; 95% CI, 15.8 to 26.3 Inflammatory process 18 = 8.0%; 5.1 to 12.4Endometrioma 32 = 14.2%; 10.3 to 19.5 Cystic teratoma 32 = 14.2%; 10.3 to 19.5 Leiomyoma 11 = 4.9%; 2.7 to 8.7 Fibroma-thecoma 6 = 2.7%; 1.1 to 5.9 Cystadenoma 35 = 15.5%; 11.5 to 21 Cystadenofibroma 3 = 1.3%; 0.3 to 4.1 

Comme--Clinica--Patienmaligna--Includ--Age rabe premQuality Size of sample NumbePatient collectealready Applica(all had 

Schneider, Schneider, Reed, et al., 1993 

Geographical location: Tucson, AZ Dates: 

Age: Mean: 53 Median: 53 Range: 10-79 

Symptomatic (n [%]): NR Detected by exam (n [%]): 

Of the 55 enrolled: 14/55 were malignant = 25.5%; 95% CI, 16.6 to 39.5 2/55 were borderline tumors = 3.6%; 0.5 

Comme--Clinica--Patientherefo
D-10

Evidence Table 1 (continued) 

Study Study Design Patients Clinical Presentation Results Comm

#4830 

NR; published 1993 Size of population: 55 Other: Patients undergoing surgery for adnexal mass 

Menopausal status (n [%]): Pre (< 45): 22 (40%) Post (> 55): 33 (60%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR 

NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

to13.5 39/55 were benign 70.9%; 60.5 to 83.4 Malignant: Endometriod cancer 6 = 10.9%; 95% CI, 5.2 to 22.9 Adenocarcinoma, undifferentiated 3 = 5.5%; 1.5 to 16 Carcinosarcoma 1 = 1.8%; 0 to 11 Clear-cell adenocarcinoma 1 = 1.8%; 0 to 11Krukenberg tumor (primary gastric) 1 = 1.8%; 0 to 11 Malignant Brenner tumor 1 = 1.8%; 0 to 11 Leiomyosarcoma 1 = 1.8%; 0 to 11 Borderline tumors (LMP): Serous cystadenocarcinoma 2 = 3.6%; 95% CI, 0.5 to13.5 Benign: Serous cystadenoma 12 = 21.8%; 95% CI, 13.6 to 35.6 Endometriosis 4 = 7.3%; 2.7 to 18.4 Mucinous cystadenoma 3 = 5.5%; 1.5 to 16 Follicular cyst 3 = 5.5%; 1.5 to 16 Adenofibroma 1 = 1.8%; 0 to 11 Brenner tumor 1 = 1.8%; 0 to 11 Corpus luteum cyst 1 = 1.8%; 0 to 11 Fibroma 1 = 1.8%; 0 to 11 Mature teratoma 1 = 1.8%; 0 to 11 Mixed stromal cell tumor 1 = 1.8%; 0 to 11 Serous Cystadenofibroma 1 = 1.8%; 0 to 11 Leiomyoma 4 = 7.3%; 2.7 to 18.4 Paraovarian cyst 3 = 5.5%; 1.5 to 16 Hydrosalpinx 2 = 3.6%; 0.5 to 13.5 Peritoneal inclusion cyst 1 = 1.8%; 0 to 11 

over-reQuality Size of sample NumbePatient Applica(all had 

Scoutt, McCarthy, Lange, et al., 1994 

Geographical location: Connecticut Dates: 

1988-1990 

Age: Median: 40 Range: 2-87 Menopausal status 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR 

Benign: 87/109 (79.8%; 95% CI, 72.8 to 87.5) 17 (15.6%; 10.2 to 24.1) leiomyoma 19 (17.4%; 11.7 to 26.1) dermoid 13 (11.9%; 7.2 to 19.8) endometrioma 

Comme--ClinicaQuality Size of 
D-11

Evidence Table 1 (continued) 

Study Study Design Patients Clinical Presentation Results Comm

#4530 

Size of population: 109 masses with MRI OtherClinical masses that underwent MRI and then biopsy 

(n [%]): NRRace/ethnicity (n [%]): NR Risk factors (n [%]): NR

Detected by imaging (n [%]): NR Combination (n [%]): 109 (100%) Additional data used for diagnosis: NR 

9 (8.3%; 4.4 to 15.4) hemorrhagic cysts 9 (8.3%; 4.4 to 15.4) simple cysts 5 (4.6%; 1.8 to 10.8) serous cystadenoma 3 (2.7%; 0.7 to 8.3) mucinous cystadenoma 3 (2.7%; 0.7 to 8.3) friboma 3 (2.7%; 0.7 to 8.3) tuboovarian abscess 3 (2.7%; 0.7 to 8.3) paratubal cyst 1 (0.9%; 0 to 5.7) fibrothecoma 1 (0.9%; 0 to 5.7) leutinized thecoma 1 (0.9%; 0 to 5.7) hematosalpinx Malignant: 22/109 (20.2%; 95% CI, 14 to 29.2) 5 (4.6%; 1.8 to 10.8) papillary serous cystadenocarcinoma 4 (3.7; 1.2 to 9.6%) metastatic adenocarcinoma 3 (2.7%; 0.7 to 8.3) mucinous cystadenocarcinoma 3 (2.7%; 0.7 to 8.3) endometroid carcinoma 2 (1.8%; 0.2 to 7.0) adenocarcinoma 1 (0.9%; 0 to 5.7) immature teratoma 1 (0.9%; 0 to 5.7) embryonal cell carcinoma 1 (0.9%; 0 to 5.7) dysgerminoma 1 (0.9%; 0 to 5.7) granulosa cell tumor 1 (0.9%; 0 to 5.7) endometrial carcinoma 

sample NumbePatient who haApplica(all had 

ShenGunther and Mannel, 2002 #2090 

Geographical location: Las Vegas, NV; Oklahoma City, OK Dates: 

Jan 1994-Dec 1994 and 

Age: Median: 58 Range: 18-86 Menopausal status (n [%]): 

Symptomatic (n [%]): NR Detected by exam (n [%]): 6% 

Benign: 57/125 (45.6%; 95% CI, 37.8 to 55.1) 22 (17.6%; 12.1 to 25.6) serous cystadenoma 3 (2.4%; 0.6 to 7.3) mucinous cystadenoma4 (3.2%; 1.1 to 8.4) friboma 

Comme--Large ascites high preQuality 
D-12

Evidence Table 1 (continued) 

Study Study Design Patients Clinical Presentation Results Comm

Jan 1999-Dec 2001 Size of population: 125 OtherPatients treated for pelvic mass

NRRace/ethnicity (n [%]): White 82% Black 9% Hispanic 2% Asian 4% American Indian 3% Risk factors (n [%]): NR

Detected by imaging (n [%]): Ultrasound 46% CT 18% Both 31% Combination (n [%]): NR Additional data used for diagnosis: NR 

2 (1.6%; 0.1 to 6.2) thecoma 5 (4%; 1.6 to 9.4) teratoma 5 (4%; 1.6 to 9.4 follicular cyst 1 (0.8%; 0 to 5) paratubal cyst 5 (4%; 1.6 to 9.4 hemorrhagic cysts 2 (1.6%; 0.1 to 6.2) tuboovarian adhesions 8 (6.4%; 3.2 to 12.5) endometrioma Borderline (LMP): 12/125 (9.6%; 95% CI, 5.6 to 16.4) 8 (6.4%; 3.2 to 12.5) serous low malignant potential 4 (3.2%; 1.1 to 8.4) mucinous low malignant potential Malignant: 56/125 (44.8%; 37.1 to 54.3) 39 (31.2%; 24.2 to 40.3) serous cystadenocarcinoma 2 (1.6%; 0.1 to 6.2) mucinous cystadenocarcinoma 4 (3.2%; 1.1 to 8.4) endometroid carcinoma 4 (3.2%; 1.1 to 8.4) primary peritoneal carcinoma 2 (1.6%; 0.1 to 6.2) clear cell carcinoma 1 (0.8%; 0 to 5) undifferentiated adenocarcinoma 2 (1.6%; 0 to 5) immature teratoma Stage 1 = 11 Stage 2 = 1 Stage 3 = 33 Stage 4 = 5 Unstaged = 6 

Size of sample NumbePatient frames prevaleApplica(all had 

Smikle, Lunt, and Hankins, 1995 #6290 

Geographical location: San Antonio, TX Dates: 

Jun 1990-Aug 1992 Size of population: 

Age: Range: < 20 and > 61 Menopausal status (n [%]): Pre (< 45): NR Peri (45-55): NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging 

Benign: 169/195 (86.7%; 95% CI, 82.1 to 95.0) 37 (19.0%; 14.3 to 25.3) serous cystadenoma 11 (5.6%; 3.2 to 10.1) mucinous cystadenoma 26 (13.3%; 9.4 to 19.1) hemorrhagic cysts 

Comme--ClinicaQuality Size of sample Numbe
D-13

Evidence Table 1 (continued) 

Study Study Design Patients Clinical Presentation Results Comm

195 Other

Surgical cases with preoperative diagnosis of pelvic mass

Post (> 55): 78 (40%) 51 and older Race/ethnicity (n [%]): NR Risk factors (n [%]): NR 

(n [%]): NR Combination (n [%]): 195 (100%) Additional data used for diagnosis: NR 

20 (10.3%; 6.8 to 15.6) endometriosis 17 (8.7%; 5.5 to 13.8) teratoma (mature) 7 (3.6%; 1.7 to 7.6) cyst of Morgagni Data not provided for 27 cases Malignant: 26/195 (13.3%; 95% CI, 9.4 to 19.1) 14 (7.2%; 4.3 to 11.9) serous cystadenocarcinoma 5 (2.6%; 1.0 to 6.3) mucinous cystadenocarcinoma 1 (0.5%; 0 to 3.2) endometroid carcinoma 4 (2.1%; 0.7 to 5.4) undifferentiated adenocarcinoma 1 (0.6%; 0 to 3.2) granulosa cell carcinoma Benign mass by age: Age ≤ 50 (n = 117) 

Serous cystadenoma: 19 (16.2%; 95% CI, 10.9 to 24.4) Functional cyst: 20 (17.1%; 11.6 to 25.4) Hydrosalpinx/tuboovarian abscess: 18 (15.4%; 10.1 to 23.5%) Endometriosis: 16 (13.7%; 8.7 to 21.5) Mature teratoma: 11 (9.4%; 5.4 to 16.5) Mucinous cystadenoma: 3 (2.6%; 0.6 to 7.8) Cyst of Morgagni: 4 (3.4%; 1.1 to 8.9) Age > 50 (n = 78) Serous cystadenoma: 18 (23.1%;15.6 to 34.4) Functional cyst: 6 (7.7%; 3.5 to 16.5) Hydrosalpinx/ tuboovarian abscess: 5 (6.4%; 2.6 to 14.9) Endometriosis: 4 (5.1%; 1.8 to13.2) Mature teratoma: 6 (7.7%; 3.5 to 16.5) Mucinous cystadenoma: 8 (10.3%; 5.3 to 19.7) Cyst of Morgagni: 3 (3.9%; 1.0 to 11.5%) 

wide CIPatient cases) Applica(all had 

Troiano, QuedensCase, and Taylor, 1997 

Geographical location: New Haven, CT Dates: 

1991-1996 

Age: Mean: Approx. 45 Range: 18-79 Menopausal status 

Symptomatic (n [%]): NR Detected by exam (n [%]): 100% suspected mass on 

Malignant: 17/144 = 11.8%; 95% CI, 7.6 to 18.4 Serous cystadenocarcinoma 7 = 4.9%; 2.3 to 10 Mucinous cystadenocarcinoma 1 = 0.7%; 0 

Comme--Not albetter gerror in 
D-14

Evidence Table 1 (continued) 

Study Study Design Patients Clinical Presentation Results Comm

#3680 

Size of population: 144 patients Other Patients with suspected mass on exam and referred for US; not all went on to surgery, but all had followup 

(n [%]): Pre (< 45): 101 (70%) Post (> 55): 42 (29%) Missing 1 case Race/ethnicity (n [%]): NR Risk factors (n [%]): NR 

exam Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

to 4.3 Endometrioid carcinoma 1 = 0.7%; 0 to 4.3 Embryonal cell carcinoma 1 = 0.7%; 0 to 4.3Granulosa cell 1 = 0.7%; 0 to 4.3 Fallopian tube carcinoma 1 = 0.7%; 0 to 4.3 Endometrial 1 = 0.7%; 0 to 4.3 Metastatic 4 = 2.8%; 0.9 to 7.3 Borderline tumors 3/144 = 2.1%; 0.5 to 6.3 Borderline papillary serous 3 = 2.1%; 0.5 to 6.3 Benign: 97/144 = 67.4%; 95% CI, 60.3 to 75.3 Serous cystadenoma 1 = 0.7%; 0 to 4.3 Mucinous cystadenoma 3 = 2.1%; 0.5 to 6.3Functional ovarian cyst 3 = 2.1%; 0.5 to 6.3Paratubal cyst 4 = 2.8%; 0.9 to 7.3 Ovarian dermoid cyst 4 = 2.8%; 0.9 to 7.3 Fibroma or thecoma 2 = 1.4%; 0.1 to 5.4 Cystadenofibroma 1 = 0.7%; 0 to 4.3 Endometriosis or hemorrhagic cyst 16 = 11.1%; 7 to 17.6 Leiomyomas or adenomyosis 43 29.9%; 23.4 to 38.3 Leiomyomas with endometriosis 6 = 4.2%; 1.8 to 9.1 Leiomyomas with simple ovarian cyst 2 = 1.4%; 0.1 to 5.4 Leiomyomas with paratubal cyst 1 = 0.7%; 0 to 4.3 Leiomyomas with ovarian fibroma 1 = 0.7%; 0 to 4.3 Leiomyomas with Brenner tumor 1 = 0.7%; 0 to 4.3 Leiomyomas with ovarian cystadenoma 2 = 1.4%; 0.1 to 5.4 Cirrhosis 1 = 0.7%; 0 to 4.3 Pregnancy 1 = 0.7%; 0 to 4.3 No biopsy because ultrasound negative: 27 = 18.7%; 95% CI, 13.4 to 26.3 

Quality Size of sample NumbePatient others – exam) Applica(not all followu

Twickler, Forte, SantosGeographical location: Dallas, TX Age: Mean: 38.6 Range: 15-80 Symptomatic (n [%]): NR Malignant: 14/244 = 5.7%; 95% CI, 3.4 to 9.6 Serous 4 = 1.6%; 0.5 to 4.4 Comme

--Not albetter g
D-15

Evidence Table 1 (continued) 

Study Study Design Patients Clinical Presentation Results Comm

Ramos, et al., 1999 #3080 

Dates: 

Feb 1993-Aug 1996 Size of population: 244 women Other 304 had ultrasound for mass, and 217 had surgery and another 27 had ultrasound followup, for a total of 244 

Menopausal status (n [%]): NRRace/ethnicity (n [%]): NR Risk factors (n [%]): NR 

Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

Metastasis 4 = 1.6%; 0.5 to 4.4 Adenocarcinoma 2 = 0.8%; 0.05 to 3.2 Mucinous 1 = 0.4%; 0 to 2.6 Small cell 1 = 0.4%; 0 to 2.6 Sarcoma 1 = 0.4%; 0 to 2.6 Mixed germ cell 1 = 0.4%; 0 to 2.6 Borderline tumors: 16/244 = 6.6%; 95% CI, 4.1 to 10.6 Mucinous 8 = 3.3%; 1.6 to 6.5 Serous 5 = 2%; 0.8 to 4.9 Granulosa cell 2 = 0.8%; 0.05 to 3.2 Endometrioid 1 = 0.4%; 0 to 2.6 Benign: 214/244 = 87.7%; 83.7 to 91.9 Simple functional cyst 69 = 28.3%; 23.2 to 34.5 PID mass 25 = 10.2%; 7.1 to 14.9 Endometriomas 13 = 5.3%; 3.1 to 9.1 No ovarian mass 7 = 2.9%; 1.3 to 6 Non-defined ovarian cystic disease 8 = 3.3%; 1.6 to 6.5 Para-ovarian cyst 1 = 0.4%; 0 to 2.6 Paratubal cyst 1 = 0.4%; 0 to 2.6 Fibrovascular ampullary mass 1 = 0.4%; 0 to 2.6 Ectopic mass 1 = 0.4%; 0 to 2.6 Ovarian lymphocele 1 = 0.4%; 0 to 2.6 Peritoneal cyst 1 = 0.4%; 0 to 2.6 Mesonephric cyst 1 = 0.4%; 0 to 2.6 Dermoid/cystic teratoma 35 = 14.3%; 10.6 to 19.5 Serous cystadenoma 19 = 7.8%; 5.1 to 12 Cystadenofibroma 13 = 5.3%; 3.1 to 0.1 Mucinous cystadenoma 7 = 2.9%; 1.3 to 6 Cystadenoma (unspecified) 3 = 1.2%; 0.3 to 3.8 Fibroma 2 = 0.8%; 0.05 to 3.2 Fibrothecoma 1 = 0.4%; 0 to 2.6 Seromucinous 1 = 0.4%; 0 to 2.6 Other 4 = 1.6%; 0.5 to 4.4 

possibiQuality Size of sample NumbePatient Applica(not all lost to f

van Nagell Jr., DePriest, Reedy, et 

Geographical location: Kentucky Dates: 

Age: Mean (SD): 54.7 (10.7) Range: 25-92 

Symptomatic (n [%]): 0 Detected by exam (n [%]): 

Benign: 155/14,469 (1.1%; 95% CI, 0.9 to 1.2) 78 (0.5%; 0.4 to 0.7) serous cystadenomas 25 (0.2%; 0.1 to 0.3) endometriomas 

Quality Size of sample Numbe
D-16

Evidence Table 1 (continued) 

Study Study Design Patients Clinical Presentation Results Comm

al., 2000 #2730 

1987-1999 Size of population: 17 cancers/14,469 (actually 3 were borderline) Screening study (most had positive family history; 180 had a biopsy) 

Menopausal status (n [%]): All ≥ 50 or ≥ 25 with family 

history Race/ethnicity (n [%]): NR Risk factors (n [%]): Family history of: Ovarian cancer: 23% Breast cancer: 34% Colon cancer: 23% 

3/17 cancers were palpated on exam but not detected on exam Detected by imaging (n [%]): 100% had TVUS Combination (n [%]): NR Additional data used for diagnosis: NR 

10 (0.07%; 0.04 to 0.1) mucinuos cystadenomas 11 (0.08%; 0.04 to 0.1) cystic teratomas 13 (0.09%; 0.05 to 0.2) fibroma/thecoma 4 (0.03%; 0.01 to 0.07) leiomyoma 14 (0.1%; 0.06 to 0.2) hydrosaplinx/ paratubal cyst Borderline (LMP): 3/14,469 (0.02%; 95% CI, 0 to 0.06) All 3 serous low malignant potential Malignant: 14/14469 (0.1%; 95% CI, 0.06 to 0.2) 1 (0.01%; 0 to 0.04) serous cystadenocarcinoma 1 (0.01%; 0 to 0.04) mucinous cystadenocarcinoma 3 (0.02%; 0 to 0.06) endometroid carcinoma6 (0.04%; 0.02 to 0.09) undifferentiated adenocarcinoma 3 (0.02%; 0 to 0.06) granulosa cell carcinoma 

study wPatient history) Applica(all with 

Vasilev, Schlaerth, Campeau, et al., 1988 #6770 

Geographical location: Los Angeles, CA Dates: 

Apr 1984-Feb 1986 Size of population: 182 non-consecutive patients with pelvic mass Other 

Age: NR Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): 

Malignant: 15/182 = 8.2%; 95% CI, 5.1 to 13.4 Serous cystadenocarcinoma 4 = 2.2%; 0.7 to 5.8 Mucinous cystadenocarcinoma 2 = 1.1%; 0.1 to 4.3 Endometrioid carcinoma 1 = 0.5%; 0 to 3.4 Leiomyosarcoma1 = 0.5%; 0 to 3.4 Gastric Krukenberg tumor 1 = 0.5%; 0 to 3.4Hypernephroma 1 = 0.5%; 0 to 3.4 

Comme--8 of 1were m--Selecseries nQuality Size of sample NumbePatient 
D-17

Evidence Table 1 (continued) 

Study Study Design Patients Clinical Presentation Results Comm

Non-consecutive series of patients scheduled for surgery for adnexal mass 

NR NR 

Additional data used for diagnosis: NR 

Lymphoma 1 = 0.5%; 0 to 3.4 Melanoma 1 = 0.5%; 0 to 3.4 Uterine leiomyosarcoma 3 = 1.6%; 0.4 to 5 Borderline tumors 3/182 = 1.6%; 95% CI, 0.4 to 5 Serous low malignant potential 1 = 0.5%; 0 to 3.4 Mucinous low malignant potential 2 = 1.1%; 0.1 to 4.3 Benign: 164/182 = 90.1%; 95 % CI, 85.9 to 94.5 Adhesions complex 2 = 1.1%; 0.1 to 4.3 Paratubal cysts 6 = 3.3%; 1.4 to 7.3 Ectopic pregnancy 2 = 1.1%; 0.1 to 4.3 Acute salpingitis 12 = 6.6%; 3.8 to 11.4 Chronic salpingitis 3 = 1.6%; 0.4 to 5 Serous cystadenoma 9 = 4.9%; 2.6 to 9.4 Mucinous cystadenoma 4 = 2.2%; 0.7 to 5.8Benign cystic teratoma 13 = 7.1%; 4.2 to 12.1 Fibroma 2 = 1.1%; 0.1 to 4.3 Brenner tumor 1 = 0.5%; 0 to 3.4 Endometrioma 5 = 2.7%; 1.1 to 6.5 Simple ovarian cyst 2 = 1.1%; 0.1 to 4.3 Leiomyoma 71 = 39%; 32.6 to 46.7 adenomyosis 9 = 4.9%; 2.6 to 9.4 Leiomyomas with endometriosis 2 = 1.1%; 0.1 to 4.3 Leiomyomas with adenomyosis 8 = 4.4%; 2.2 to 8.7 Leiomyomas with chronic salpingitis 5 = 2.7%; 1.1 to 6.5 Leiomyomas with endometriosis and adenomyosis 1 = 0.5%; 0 to 3.4 Leiomyomas with Brenner tumor and mucinous cystadenoma 1 = 0.5%; 0 to 3.4 Leiomyomas with serous cystadenoma 1 = 0.5%; 0 to 3.4 Leiomyomas with adenomyosis and chronic salpingitis 2 = 1.1%; 0.1 to 4.3 Leiomyomas with endometriosis and chronic salpingitis 1 = 0.5%; 0 to 3.4 

Applica(not all 
D-18

Evidence Table 1 (continued) 

Study Study Design Patients Clinical Presentation Results Comm

Leiomyomas and salpingitis and paratubal cyst 1 = 0.5%; 0 to 3.4 Cystadenofibroma and Leiomyoma and endometriosis 1 = 0.5%; 0 to 3.4 
D-19

Evidence Table 2: Question 2: What are the sensitivity, specificity, and reliability of the bimanual pelvic examination? 

Study Study Design Patients Clinical 

Presentation 

Clinical Setting of Exam 

Results 

Adonakis, Paraskevaidis, Tsiga, et al., 1996 #810 

Geographical location: Greece Dates: Mar 1991-Jun 1993 Size of population: 2000 Screening study Reference standard: US if BME abnormal or ambiguous; surgery if US positive; 12-month CA-125 if negative Reference standard applied to all test negatives?: Yes

Test reliability established?: No; performed by 3 gynecological oncologists Statistical tests used: Se, Sp Blinding: Yes

Definition of positive and negative on screening test: Positive exam: palpable adnexal mass Ambiguous: origin of mass unclear or inadequate exam

Age: Mean (SD): 58.1 (6.9) Range: 45-80 Menopausal status (n [%]): Pre: 405 (20%) Peri: 293 (15%) Post: 1302 (65%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Women > 45, no evidence of adnexal pathology, agreed to participate Exclusion criteria: History of ovarian cancer or any other malignancy, history of bilateral oophorectomy, ascites 

Symptomatic (n [%]): 0 (0%) Detected by exam (n [%]): 50 (3%) positive exam 115 (6%) “ambiguous” exam Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: 

Women with elevated CA-125 or and abnormal or ambiguous BME were recalled for TVUS. Only women with +TVUS were referred for further management 

Screening study 1) Benign vs. malignant: 

 Dis+ Dis- Tot T+ 2 57 59 

T- 1 1940 1941 Tot 3 1997 2000  Lower Upper  Value 95% CI 95% CI Se 66.7% 13.3% 100.0%Sp 97.1% 96.4% 97.9% PPV 3.4% 0.0% 8.0% NPV 99.9% 99.8% 100.0%
D-20

Evidence Table 2 (continued) Study Study Design Patients Clinical 

Presentation 

Clinical Setting of Exam 

Results 

Andolf, Jorgensen, and Astedt, 1990 #1200 

Geographical location: Sweden Dates: Oct 1984-Jul 1987 Size of population: 801 Screening study For women at high risk for ovarian cancer Reference standard: All had US and some had biopsies Reference standard applied to all test negatives?: NoTest reliability established?: No 

Statistical tests used: NoneBlinding: NR

Definition of positive and negative on screening test: NR

Age: Range: 40-70 Menopausal status (n [%]): NR Race/ethnicity (n [%]): NRRisk factors (n [%]): Family history: 190 (23.7%) Inclusion criteria: Women older than 40 with either abdominal pain, nulliparity, family history of breast, ovarian, or endometrial cancer, or previous history of cancer Exclusion criteria: NR 

Symptomatic (n [%]): 419 (52.3%) Detected by exam (n [%]): NR Detected by imaging (n [%]): 

NR Combination (n [%]): NR Additional data used for diagnosis: NR 

One gynecologist clinical examiner, and then a midwife did the US 

1) Abnormal vs. normal US: 

 Dis+ Dis- Tot 

T+ 55 51 106 T- 108 587 695 Tot 163 638 801  Lower Upper  Value 95% CI 95% CI Se 33.7% 26.5% 41.0% Sp 92.0% 89.9% 94.1% PPV 51.9% 42.4% 61.4% NPV 84.5% 81.8% 87.2% 
D-21

Evidence Table 2 (continued) Study Study Design Patients Clinical 

Presentation 

Clinical Setting of Exam 

Results 

Balbi, Musone, Menditto, et al., 2001 #2320 

Geographical location: Naples, Italy Dates: Jan 1996-Mar 2000 Size of population: 92 Case series Reference standard: Histopathological diagnosis Reference standard applied to all test negatives?: No – 18 women with “clearly benign” masses not verified; 2 patients with “clearly malignant” disease (metastases) also excluded Test reliability established?: Not for PE or CA-72-4 Uncertain for US and RI Yes for CA-125 Statistical tests used: Se, Sp, multivariate logistic analysis Blinding: NRDefinition of positive and negative on screening test: PE: “malignant clinical impression” 

Age: Range: 40-80 Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: “Women with a pelvic mass originating in the ovary” Exclusion criteria: 

NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

Women with pelvic mass prior to surgery. Physical exam by standard protocol. Examiner was asked to predict benign or malignant. 

1) Benign vs. malignant: 

 Dis+ Dis- Tot T+ 20 13 33 

T- 2 37 39 Tot 22 50 72  Lower Upper  Value 95% CI 95% CI Se 90.0% 77.5% 100.0%Sp 74.0% 61.8% 86.2% PPV 60.6% 43.9% 77.3% NPV 94.9% 87.9% 100.0%
D-22

Evidence Table 2 (continued) Study Study Design Patients Clinical 

Presentation 

Clinical Setting of Exam 

Results 

Buckshee, Temsu, Bhatla, et al., 1998 #710 

Geographical location: India Dates: May 1995-Apr 1997 Size of population: 34 non-consecutive women with 36 tumors Other: Women scheduled for surgery for adnexal mass Reference standard: Biopsy Reference standard applied to all test negatives?: Yes Test reliability established?: NoStatistical tests used: McNemar testBlinding: YesDefinition of positive and negative on screening test: Yes Clinical diagnosisbenign vs. malignant 

Age: Range: 20 to > 50 Menopausal status (n [%]): Pre (< 45): NR Peri (45-55): NR Post (> 55): 5 > 50 Race/ethnicity (n [%]): Indian Risk factors (n [%]): Family history: 1 (3%) Inclusion criteria: Scheduled for surgery Exclusion criteria: 

Known cancer and with evidence of extensive/metastatic disease on US or CT scan 

Symptomatic (n [%]): NR Detected by exam (n [%]): 10 (2.8%) Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

One gynecologist clinical examiner 

1) Malignant vs. benign: 

 Dis+ Dis- Tot 

T+ 7 3 10 T- 2 24 26 Tot 9 27 36  Lower Upper  Value 95% CI 95% CI Se 77.8% 50.6% 100.0%Sp 88.9% 77.0% 100.0%PPV 70.0% 41.6% 98.4% NPV 92.3% 82.1% 100.0%
D-23

Evidence Table 2 (continued) Study Study Design Patients Clinical 

Presentation 

Clinical Setting of Exam 

Results 

Dowd, Quinn, Rome, and Koh, 199 #4680 

Geographical location: Melbourne, Australia Dates: 1978-1989 Size of population: 264 (n = 225 with definite clinical impression) Case series Reference standard: Pathology Reference standard applied to all test negatives?: Yes

Test reliability established?: Not referenced or measured Statistical tests used: Se, Sp, NPV, PPV Blinding: No

Definition of positive and negative on screening test: “Mass described as ‘hard, irregular, fixed, attached to other structures’, or associated with ascites, or a specific statement from a consultant gynaecologist of the suspected malignant nature of the mass” 

Age: Mean: 47 Range: 15-89 Menopausal status (n [%]): Pre (< 45): 78 (61%)Peri (45-55): Post (> 55): 50 (39%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Suspected pelvic mass, CA-125 level available Exclusion criteria: 

Screening, inadequate documentation of clinical findings of pathology 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

Not described; presumably, in outpatient setting 

1) Benign vs. malignant - all patients: 

 Dis+ Dis- Tot T+ 56 15 71 

T- 54 100 154 Tot 110 115 225  Lower Upper  Value 95% CI 95% CI Se 51.0% 41.7% 60.3% Sp 87.0% 80.8% 93.2% PPV 79.0% 69.5% 88.5% NPV 65.0% 57.5% 72.5% 

2) Other: Values also reported by menopausal status, but insufficient data to construct 2x2 table: Premenopausal: Sensitivity 31%, specificity 95%, PPV 76%, NPV 75% Postmenopausal: Sensitivity 59%, specificity 75%, PPV 79%, NPV 54% 
D-24

Evidence Table 2 (continued) Study Study Design Patients Clinical 

Presentation 

Clinical Setting of Exam 

Results 

Finkler, Benacerraf, Lavin, et al., 1988 #1230 

Geographical location: Boston, MA Dates: Nov 1986-Apr 1987 Size of population: 106 Other: Consecutive patients with adnexal mass scheduled for surgery Reference standard: Biopsy Reference standard applied to all test negatives?: Yes

Test reliability established?: NoStatistical tests used: Fisher’s exact testBlinding: NR

Definition of positive and negative on screening test: Clinicians asked to judge the clinical appearance of the mass based on history and physical exam combined

Age: Mean: 45.2 Range: 17-84 Menopausal status (n [%]): Pre (< 45): 74 (69.8%) Post (> 55): 32 (30.2%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Adnexal mass scheduled for surgeryExclusion criteria: US unavailable or uninterpretable; pregnancy; known cancer 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR 

Additional data used for diagnosis: NR 

One gynecologist examiner who gave his/her verbal clinical impression before surgery 

1) Total study - clinical impression is test, and malignant (yes/no) is disease state: 

 Dis+ Dis- Tot T+ 16 6 22 

T- 21 59 80 Tot 37 65 102  Lower Upper  Value 95% CI 95% CI Se 43.2% 27.3% 59.2% Sp 90.8% 83.7% 97.8% PPV 72.7% 54.1% 91.3% NPV 73.8% 64.1% 83.4% 

2) Premenopausal group: 

 Dis+ Dis- Tot T+ 3 4 7 T- 15 48 63 Tot 18 52 70  Lower Upper  Value 95% CI 95% CI Se 16.7% 0.0% 33.9% Sp 92.3% 85.1% 99.6% PPV 42.9% 6.2% 79.5% NPV 76.2% 65.7% 86.7% 

3) Postmenopausal group: 

 Dis+ Dis- Tot T+ 13 2 15 T- 6 11 17 Tot 19 13 32  Lower Upper  Value 95% CI 95% CI Se 68.4% 47.5% 89.3% Sp 84.6% 65.0% 100.0%PPV 86.7% 69.5% 100.0%NPV 64.7% 42.0% 87.4% 
D-25

Evidence Table 2 (continued) Study Study Design Patients Clinical 

Presentation 

Clinical Setting of Exam 

Results 

Grover and Quinn, 1995 #830 

Geographical location: Melbourne, Australia Dates: NR Size of population: 2623 Screening study Healthy volunteers Reference standard: US if mass or elevated CA-125 Surgery or 12-month followup questionnaire Reference standard applied to all test negatives?: Yes – 12-month followup questionnaire for all Test reliability established?: No; single examinerStatistical tests used: Chi-square Blinding: No

Definition of positive and negative on screening test: Premenopausal: “larger than normal” Postmenopausal: palpable 

Age: Mean: 51 Range: 25-92 Menopausal status (n [%]): Pre (< 45): 1121 (43%) Peri (45-55): 384 (15%) Post (> 55): 1118 (42%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Asymptomatic, recruited (not clear how) Exclusion criteria: NR 

Symptomatic (n [%]): 0 (0%) Detected by exam (n [%]): NR Detected by imaging (n [%]): 

NR Combination (n [%]): NR Additional data used for diagnosis: NR 

Single examiner 1) All women: 

 Dis+ Dis- Tot T+ 0 40 40 

T- 1 2582 2583 Tot 1 2622 2623  Lower Upper  Value 95% CI 95% CI Se 0.0% 0.0% 100.0%Sp 98.5% 98.0% 98.9% PPV 0.0% 0.0% 7.5% NPV 100.0% 99.9% 100.0%

Unable to calculate by menopausal status. 
D-26

Evidence Table 2 (continued) Study Study Design Patients Clinical 

Presentation 

Clinical Setting of Exam 

Results 

Jacobs, Stabile, Bridges, et al., 1988 #6830 

Geographical location: London, UK Dates: Patients recruited over a 6-month period; published 1988 Size of population: 1010 women Screening study Reference standard: Biopsy or 12-month followup Reference standard applied to all test negatives?: All had followup, and a few had biopsyTest reliability established?: No Statistical tests used: Chi-squareBlinding: NRDefinition of positive and negative on screening test: “Palpable pelvic mass of any size that could be clinically distinguished as being separate from the uterus and GI tract” 

Age: Mean: 54 Range: 45-83 Menopausal status (n [%]): Post (> 55): 1010 (100%) Race/ethnicity (n [%]): NRRisk factors (n [%]): 18 (1.8%) had history of breast cancer Inclusion criteria: Age over 45 and postmenopausal Exclusion criteria: 

History of ovarian cancer or undergoing treatment for other cancer; history of bilateral oophorectomy 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

One clinical examiner 1) Abnormal US as gold standard: 

 Dis+ Dis- Tot T+ 11 17 28 

T- 2 980 982 Tot 13 997 1010  Lower Upper  Value 95% CI 95% CI Se 84.6% 65.0% 100.0%Sp 98.3% 97.5% 99.1% PPV 39.3% 21.2% 57.4% NPV 99.8% 99.5% 100.0%

2) Cancer yes/no: 

 Dis+ Dis- Tot T+ 1 27 28 T- 0 982 982 Tot 1 1009 1010  Lower Upper  Value 95% CI 95% CI Se 100.0% 0.0% 100.0%Sp 97.3% 96.3% 98.3% PPV 3.6% 0.0% 10.4% NPV 100.0% 99.7% 100.0%
D-27

Evidence Table 2 (continued) Study Study Design Patients Clinical 

Presentation 

Clinical Setting of Exam 

Results 

Ong, Duffy, and Murphy, 1996 #780 

Geographical location: Dublin, Ireland Dates: Jan 1993-Feb 1995 Size of population: 86 undergoing laparotomy Other: Patients undergoing surgeryReference standard: Biopsy Reference standard applied to all test negatives?: Yes

Test reliability established?: NoStatistical tests used: Se, SpBlinding: NR

Definition of positive and negative on screening test: NR (retrospective chart review)

Age: NR Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: NR Exclusion criteria: Pregnant; missing information or no US 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

One gynecologist examiner 

1) Ovarian mass yes/no by US: 

 Dis+ Dis- Tot 

T+ 46 9 55 T- 18 13 31 Tot 64 22 86  Lower Upper  Value 95% CI 95% CI Se 71.9% 60.9% 82.9% Sp 59.1% 38.5% 79.6% PPV 83.6% 73.9% 93.4% NPV 41.9% 24.6% 59.3% 

2) Uterine mass: 

 Dis+ Dis- Tot T+ 14 5 19 T- 4 63 67 Tot 18 68 86  Lower Upper  Value 95% CI 95% CI Se 77.8% 58.6% 97.0% Sp 92.6% 86.4% 98.9% PPV 73.7% 53.9% 93.5% NPV 94.0% 88.4% 99.7% 
D-28

Evidence Table 2 (continued) Study Study Design Patients Clinical 

Presentation 

Clinical Setting of Exam 

Results 

Padilla, Radosevich, and Milad, 2000 #460 

Geographical location: Chicago, IL Dates: Mar 1997-Mar 1998 Size of population: 82 adnexal masses in 140 patients undergoing surgery Other: Women undergoing laparotomy Reference standard: Surgery Reference standard applied to all test negatives?: Yes

Test reliability established?: NoStatistical tests used: Youden j statistic, Se, SpBlinding: NR

Definition of positive and negative on screening test: Adnexal mass defined as approx. 5 cm or more in greatest diameter

Age: Mean: 39.3 Menopausal status (n [%]): Pre (< 45): NR Peri (45-55): NR Post (> 55): 14 (10%) Race/ethnicity (n [%]): NRRisk factors (n [%]): NR Inclusion criteria: Many indications for surgery, including sterilization Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR 

Additional data used for diagnosis: NR 

Exam under anesthesia by attendings, residents, and medical students 

1) Left adnexa by attending: 

 Dis+ Dis- Tot T+ 16 9 25 

T- 33 69 102 Tot 49 78 127  Lower Upper  Value 95% CI 95% CI Se 32.7% 19.5% 45.8% Sp 88.5% 81.4% 95.6% PPV 64.0% 45.2% 82.8% NPV 67.6% 58.6% 76.7% 

2) Right adnexa by attending: 

 Dis+ Dis- Tot T+ 7 20 27 T- 26 74 100 Tot 33 94 127  Lower Upper  Value 95% CI 95% CI Se 21.2% 7.3% 35.2% Sp 78.7% 70.4% 87.0% PPV 25.9% 9.4% 42.5% NPV 74.0% 65.4% 82.6% 

3) Left adnexa by resident: 

 Dis+ Dis- Tot T+ 18 8 26 T- 31 81 112 Tot 49 89 138  Lower Upper  Value 95% CI 95% CI Se 36.7% 23.2% 50.2% Sp 91.0% 85.1% 97.0% PPV 69.2% 51.5% 87.0% NPV 72.3% 64.0% 80.6% 

4) Right adnexa by resident: 
D-29

Evidence Table 2 (continued) Study Study Design Patients Clinical 

Presentation 

Clinical Setting of Exam 

Results 

 Dis+ Dis- Tot T+ 9 14 23 

T- 24 91 115 Tot 33 105 138  Lower Upper  Value 95% CI 95% CI Se 27.3% 12.1% 42.5% Sp 86.7% 80.2% 93.2% PPV 39.1% 19.2% 59.1% NPV 79.1% 71.7% 86.6% 

5) Left adnexa by student: 

 Dis+ Dis- Tot T+ 11 6 17 T- 38 42 80 Tot 49 48 97  Lower Upper  Value 95% CI 95% CI Se 22.4% 10.8% 34.1% Sp 87.5% 78.1% 96.9% PPV 64.7% 42.0% 87.4% NPV 52.5% 41.6% 63.4% 

6) Right adnexa by student: 

 Dis+ Dis- Tot T+ 5 5 10 T- 28 59 87 Tot 33 64 97  Lower Upper  Value 95% CI 95% CI Se 15.2% 2.9% 27.4% Sp 92.2% 85.6% 98.8% PPV 50.0% 19.0% 81.0% NPV 67.8% 58.0% 77.6% 
D-30

Evidence Table 2 (continued) Study Study Design Patients Clinical 

Presentation 

Clinical Setting of Exam 

Results 

Padilla, Radosevich, and Milad, 2005 #7280 

Geographical location: Chicago, IL Dates: Mar 1997-Mar 1998 Size of population: 84 Screening study Registry Other Series of women undergoing gyn surgery Reference standard: Surgery Reference standard applied to all test negatives?: Yes

Test reliability established?: Not discussed Statistical tests used: Se, Sp, NPV, PPV, Youden’s J statistic, likelihood ratio, logistic regression Blinding: Examiners 

blinded to symptoms, indications Definition of positive and negative on screening test: Positive: Adnexal mass ≥ 5 cm 

Age: Mean (SD): 37.7 (0.93) Menopausal status (n [%]): Pre (< 45): 95.2% Peri (45-55): NR Post (> 55): NR Race/ethnicity (n [%]): NRRisk factors (n [%]): NR Other: Mean BMI 26.5 18% BMI > 30 Inclusion criteria: Women presenting for laparoscopy or laparotomy; range of indications: diagnostic laparoscopy, sterilization, suspected malignancy, etc. Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

Examination under anesthesia in dorsal lithotomy position. Bladder drained. Examiners reported adnexal size, presence of mass, uterine position, size, contour, mobility. Examiners divided into board-certified OB/GYN (n = 52), OB/GYN residents (n = 30), 3rd and 4th year 

med students (n = 40). 

1) Total all examiners – detection of adnexal mass: 

 Dis+ Dis- Tot T+ 14 10 24 

T- 76 152 228 Tot 90 162 252  Lower Upper  Value 95% CI 95% CI Se 15.6% 8.1% 23.0% Sp 93.8% 90.1% 97.5% PPV 58.3% 38.6% 78.1% NPV 66.7% 60.5% 72.8% 

(calculated by summing results for atttendings, residents, and students) 2) Attendings – detection of adnexal mass: 

 Dis+ Dis- Tot T+ 8 4 12 T- 22 50 72 Tot 30 54 84  Lower Upper  Value 95% CI 95% CI Se 28.0% 11.9% 44.1% Sp 93.0% 86.2% 99.8% PPV 66.7% 40.0% 93.3% NPV 69.4% 58.8% 80.1% 

3) Residents – detection of adnexal mass: 

 Dis+ Dis- Tot T+ 5 3 8 T- 25 51 76 Tot 30 54 84  Lower Upper  Value 95% CI 95% CI Se 16.0% 2.9% 29.1% Sp 95.0% 89.2% 100.0%
D-31

Evidence Table 2 (continued) Study Study Design Patients Clinical 

Presentation 

Clinical Setting of Exam 

Results 

PPV 62.5% 29.0% 96.0% NPV 67.1% 56.5% 77.7% 

4) Students – detection of adnexal mass: 

 Dis+ Dis- Tot T+ 1 3 4 

T- 29 51 80 Tot 30 54 84  Lower Upper  Value 95% CI 95% CI Se 4.0% 0.0% 11.0% Sp 95.0% 89.2% 100.0%PPV 25.0% 0.0% 67.4% NPV 63.8% 53.2% 74.3% 

5) Other: Likelihood of not detecting an adnexal mass increased with less experience (OR for resident 1.13, student 1.36 compared to attending, although 95% CIs cross 1). Statistically significant increase in missed diagnosis if subject with BMI > 30 (OR 2.57; 95% CI 1.36 to 4.87), and significant decrease in presence of enlarged uterus (OR 0.48; 95% CI 0.25 to 0.93). 
D-32

Evidence Table 2 (continued) Study Study Design Patients Clinical 

Presentation 

Clinical Setting of Exam 

Results 

Roman, Muderspach, Stein, et al., 1997 #6160 

Geographical location: Los Angeles, CA Dates: Jul 1992-Mar 1994 Size of population: 226 Other Nonconsecutive case series Reference standard: Surgical/path findings Reference standard applied to all test negatives?: Yes

Test reliability established?: NoStatistical tests used: Pearson, logistic regression Blinding: No

Definition of positive and negative on screening test: Positive = fixed, irregular contour, or clinical ascites 

Age: NR Menopausal status (n [%]): Pre (< 45): 181 (80.1%) Post (> 55): 45 (19.9%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Suspicious mass needing surgical evaluation Exclusion criteria: 

Emergent laparotomy, clinical or radiologic evidence of metastatic disease, U/S by gynecologist 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

By staff gynecologist in clinic 1 to 4 days prior to surgery 

Results not given for 26 women in whom mass was not palpable. 1) All women: 

 Dis+ Dis- Tot T+ 22 26 48 

T- 21 131 152 Tot 43 157 200  Lower Upper  Value 95% CI 95% CI Se 51.2% 36.3% 66.1% Sp 83.6% 77.8% 89.4% PPV 45.8% 31.7% 59.9% NPV 86.2% 80.7% 91.7% 

2) Premenopausal women: Sufficient data not provided to calculate 2x2 or CIs. 

Se 50.0%Sp 83.2%PPV 36.1%NPV 89.9%

3) Postmenopausal women: Sufficient data not provided for 2x2 table. 

Se 53.3%Sp 85.7%PPV 66.7%NPV 77.4%
D-33

Evidence Table 2 (continued) Study Study Design Patients Clinical 

Presentation 

Clinical Setting of Exam 

Results 

Schutter, Kenemans, Sohn, et al., 1994 #940 

Geographical location: Netherlands and Germany Dates: Nov 1990-Dec 1992 Size of population: 228 Other: Women presenting with pelvic mass Reference standard: Biopsy Reference standard applied to all test negatives?: Yes

Test reliability established?: NoStatistical tests used: Chi-square or Fisher’sBlinding: NR

Definition of positive and negative on screening test: Palpable mass of any size, benign vs. malignant 

Age: Mean: 63 Median: 62 Range: 45-88 Menopausal status (n [%]): Post (> 55): 100% Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: > 45 years, postmenopausal Exclusion criteria: Another cancer, indeterminate exam 

Symptomatic (n [%]): NR Detected by exam (n [%]): 199 (87%) Detected by imaging (n [%]): 28 (12%) by US Combination (n [%]): NR Additional data used for diagnosis: NR 

One gynecologist examiner 

1) Malignant vs. benign: 

 Dis+ Dis- Tot T+ 88 47 135 

T- 7 80 87 Tot 95 127 222  Lower Upper  Value 95% CI 95% CI Se 92.6% 87.4% 97.9% Sp 63.0% 54.6% 71.4% PPV 65.2% 57.1% 73.2% NPV 92.0% 86.2% 97.7% 
D-34

Evidence Table 2 (continued) Study Study Design Patients Clinical 

Presentation 

Clinical Setting of Exam 

Results 

Schutter, Sohn, Kristen, et al., 1998 #730 

Geographical location: Amsterdam, Netherlands; Wurzburg and Mainz, Germany Dates: NR (referenced in another paper by this group) Size of population: 180 (155 met inclusion/exclusion criteria) Other Case series Reference standard: Surgery/pathology Reference standard applied to all test negatives?: Yes

Test reliability established?: Lack of data on reliability discussed Statistical tests used: Se, Sp, NPV, PPV Blinding: NR

Definition of positive and negative on screening test: Abnormal: mass of any size clinically distinguishable as being separate from uterus and GI tract; examiner asked to 

Age: Mean: 63 Median: 61 Range: 45-88 Menopausal status (n [%]): Post (> 55): 180 (100%) Race/ethnicity (n [%]): NRRisk factors (n [%]): NR Inclusion criteria: Not described (referenced) Exclusion criteria: Not described (referenced) 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

Not described; presumably, in outpatient setting 

1) Benign vs. malignant (borderline = benign): 

 Dis+ Dis- Tot T+ 54 24 78 

T- 5 68 73 Tot 59 92 151  Lower Upper  Value 95% CI 95% CI Se 91.5% 84.4% 98.6% Sp 73.9% 64.9% 82.9% PPV 69.2% 59.0% 79.5% NPV 93.2% 87.4% 98.9% 
D-35

Evidence Table 2 (continued) Study Study Design Patients Clinical 

Presentation 

Clinical Setting of Exam 

Results 

state whether benign or malignant 
D-36

Evidence Table 3: Question 3: Among women with a palpable adnexal mass on exam or a mass identified by ultrasound/imaging, w

sensitivity/specificity of various evaluation modalities including ultrasound (transvaginal ultrasound, transabdominal ultrasound, color Dopultrasound), CT scan, MRI scan, and CA-125 levels for distinguishing benign from malignant masses?Study Study Design Patients Clinical Presentation Results Comm

Adonakis, Paraskevaidis, Tsiga, et al., 1996 #810 

Geographical location: Greece Dates: Mar 1991- Jun 

1993 Size of population: 2000/2000 Screening study Reference standard: Histopathology for selected positives; followup at 12 months for all others Reference standard applied to all test negatives?: 180 of the 2000 patients went onto TVUS, and only 35 these had histopathologic diagnosis; 145 verified by clinical followup of repeat exam, TVUS and/or CA125. No reported loss to followup (although not explicitly stated). Test reliability established?: BME – No CA-125 – Yes Statistical tests used: Se, Sp Blinding: NR, but exams preceded surgery 

Age: Mean (SD): 58.1(6.9) Range: 45-80 Menopausal status (n [%]): Pre: 405 (20%) Peri: 293 (15%) Post: 1302 (65%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Women > 45, no evidence of adnexal pathology, agreed to participate Exclusion criteria: Women with history of ovarian cancer or any other malignancy, history of bilateral oophorectomy, ascites 

Symptomatic (n [%]): 0 (0%) Detected by exam (n [%]): 50 (3%) + exam 115 (6%) “ambiguous” exam Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: Women with elevated CA125 or and abnormal or ambiguous BME were recalled for TVUS. Only women with +TVUS were referred for further management. 

1) CA-125 (T+ ≥ 35 U/ml) 

 Dis+ Dis- Tot T+ 3 15 18 

T- 0 1982 1982 Tot 3 1997 2000  Lower Upper  Value 95% CI 95% CI Se 100.0% 0.0% 100.0%Sp 99.2% 98.9% 99.6% PPV 16.7% 0.0% 33.9% NPV 100.0% 99.8% 100.0%

2) PE 

 Dis+ Dis- Tot T+ 2 57 59 T- 1 1940 1941 Tot 3 1997 2000  Lower Upper  Value 95% CI 95% CI Se 66.7% 13.3% 100.0%Sp 97.1% 96.4% 97.9% PPV 3.4% 0.0% 8.0% NPV 99.9% 99.8% 100.0%

Comme--1 tumother m--“AmbiTest -, aambigufurther --BordeQuality Referenleast 12 VerificastandarTest re- BME Sample but smaCIs aroestimatsensitivStatisticBlindingDefinitioCA-125
D-37

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

Definition of positive and negative on screening test: CA-125 ≥ 35 U/mL 

BME – “palpable mass” 

Alcazar and Castillo, 2005 #7460 

Geographical location: Pamplona, Spain Dates: Jan 2002 – Apr 

2004 Size of population: 60 patients 69 masses Case series Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: Se, Sp, MCNemar, Fleiss kappa index Blinding: Yes Definition of positive and negative on screening test: 2D US – presence of at least one of the following: 

Age: Mean (SD): 48.4 (16.4) Range: 17-82 Menopausal status (n [%]): Pre (< 45): 32 (53%) Post (> 55): 28 (47%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Women with diagnosis of adnexal mass who received treatment at institution in time frame for who got 2D and 3D US Exclusion criteria: “Masses in which the echo features were highly characteristic of a given pathologic condition (such as simple cyst, cystic teratoma, or endometrioma)” 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

All results for masses not patients 1) 2D (combined Doppler and morphology)

 Dis+ Dis- Tot T+ 44 3 47 

T- 1 21 22 Tot 45 24 69  Lower Upper  Value 95% CI 95% CI Se 97.8% 93.5% 100.0%Sp 87.5% 74.3% 100.0%

PPV 93.6% 86.6% 100.0%NPV 95.5% 86.8% 100.0%

2) 3D (combined) 

 Dis+ Dis- Tot T+ 44 5 49 

T- 1 19 20 Tot 45 24 69  Lower Upper  Value 95% CI 95% CI Se 97.8% 93.5% 100.0%Sp 79.2% 63.0% 95.4% 

PPV 89.8% 81.3% 98.3% NPV 95.0% 85.4% 100.0%

Comme--14 of this stupreviou(Alcaza--One p(both 2interpreinterpreblinded --Kappa interobs--No disdiagnos--No dis3D US scan --High istudy --Descrclassificscoring --3D US positive--Unclefinal tab--Unablstatus --Resulpatients --LMP tmaligna--Numbmesh eTable II --Autho
D-38

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

thick wall (> 3 mm), thick papillary projections (> 3 mm), solid areas or purely solid echogenicity = complex mass. Doppler – blood flow detected within a papillary projection, solid area, or central area of solid tumor = malignant. 3D – not mentioned. 

and Sp 0.250 --Good --TVUS Quality ReferenVerificaTest reSample StatisticBlindingDefinitio

Alcazar, Errasti, Zornoza, et al., 1999 #3110 

Geographical location: Spain Dates: Jan 1995- Feb 

1998 Size of population: 94 of 480 Other Retrospective case series Reference standard: Pathology Reference standard applied to all test negatives?: Yes Test reliability established?: Inter and intra assay coefficient for CA-125 reported Statistical tests used: Kolmogorov-Smirnov Student t-test Mann-Witney U 

Age: Mean (SD): 47.4 (16.1) Range: 17-79 Menopausal status (n [%]): Pre (< 45): 55.3% Post (> 55): 44.7% Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Sonographically suspicious adnexal mass, “presence of at least one of the following: gross septa (> 3 mm), gross papillary projections (> 3 mm), solid wall nodules, multilocularity, irregular borders or ascitis” Transvaginal color Doppler evaluation and serum CA-125 levels determined prior to surgery 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Color Doppler – all 

 Dis+ Dis- Tot T+ 49 6 55 

T- 7 32 39 Tot 56 38 94  Lower Upper  Value 95% CI 95% CI Se 87.5% 78.8% 96.2% Sp 84.2% 72.6% 95.8% PPV 89.1% 80.9% 97.3% NPV 82.1% 70.0% 94.1% 

2) CA-125 – all 

 Dis+ Dis- Tot T+ 47 12 59 T- 9 26 35 Tot 56 38 94  Lower Upper  Value 95% CI 95% CI Se 83.9% 74.3% 93.5% Sp 68.4% 53.6% 83.2% PPV 79.7% 69.4% 89.9% NPV 74.3% 59.8% 88.8% 

3) Doppler – Premenopausal 

Comme--LMP tmaligna--Inclusincreas--Pre-stasymptQuality ReferenVerificasurgery Test rereader assay c125 Sample StatisticBlindingDefinitio
D-39

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

Chi-square McNemars Test ROC Blinding: NR Definition of positive and negative on screening test: Doppler Resistance index [RI=SD] calculated for each case Malignancy suspected if lowest RI ≤ 0.45 CA-125 level CA-125 = 35 U/ml considered as suspicious for malignancy 

Definitive histopathological diagnosis Exclusion criteria: NR 

 Dis+ Dis- Tot T+ 23 5 28 

T- 3 21 24 Tot 26 26 52  Lower Upper  Value 95% CI 95% CI Se 88.5% 76.2% 100.0%Sp 80.8% 65.7% 95.9% 

PPV 82.1% 67.9% 96.3% 

NPV 87.5% 74.3% 100.0%

4) CA-125 – Premenopausal 

 Dis+ Dis- Tot T+ 22 8 30 

T- 4 18 22 Tot 26 26 52  Lower Upper  Value 95% CI 95% CI Se 84.6% 70.7% 98.5% Sp 69.2% 51.5% 86.9% 

PPV 73.3% 57.5% 89.1% 

NPV 81.8% 65.7% 97.9% 

5) Doppler – Postmenopausal 

 Dis+ Dis- Tot T+ 26 1 27 

T- 4 11 15 Tot 30 12 42  Lower Upper  Value 95% CI 95% CI Se 86.7% 74.5% 98.9% Sp 91.7% 76.1% 100.0%

PPV 96.3% 89.2% 100.0%

NPV 73.3% 50.9% 95.7% 

6) CA-125 – Postmenopausal 

 Dis+ Dis- Tot T+ 25 4 29 

T- 5 8 13
D-40

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

Tot 30 12 42 

 Lower Upper  Value 95% CI 95% CI Se 83.3% 70.0% 96.6% Sp 66.7% 40.0% 93.4% 

PPV 86.2% 73.6% 98.8% 

NPV 61.5% 35.0% 88.0% 

Alcazar, Galan, GarciaManero, et al., 2003 #1990 

Geographical location: Spain Dates: Jun 2001 to Jun 

2002 Size of population: 44 masses 41 women OtherProspective case series Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes using kappa Statistical tests used: McNemars Blinding: Second 3D reviewer blinded, 2D and first 2D reviewer not Definition of positive and negative on screening test: 

Age: Mean (SD): 49.5 Range: 23-75 Menopausal status (n [%]): Pre (< 45): 20 (49%) Post (> 55): 21 (51%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Women with the diagnosis of complex adnexal masses on 2D TVUS Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) 2D US 

 Dis+ Dis- Tot T+ 19 9 28 

T- 2 14 16 Tot 21 23 44  Lower Upper  Value 95% CI 95% CI Se 90.0% 77.2% 100.0%Sp 61.0% 41.1% 80.9% 

PPV 67.9% 50.6% 85.2% NPV 87.5% 71.3% 100.0%

2) 3D US 

 Dis+ Dis- Tot T+ 21 5 26 

T- 0 18 18 Tot 21 23 44  Lower Upper  Value 95% CI 95% CI Se 100.0% 85.7% 100.0%Sp 78.0% 61.1% 94.9% 

PPV 80.8% 65.6% 95.9% NPV 100.0% 83.3% 100.0%

Comme--Descrnumericsystem --2x2 taindividu--Pre-stasymptQuality ReferenVerificaTest reSample numberStatisticBlindingDefinitiostated 
D-41

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

Presence of one of the following fulfilled criteria for adnexal mass: A thick wall (> 3 mm) A thick septum (> 3 mm) Thick papillary projections (> 3 mm), solid areas, purely solid echogenicity 

Alcazar and LopezGarcia, 2001 #5740 

Geographical location: Spain University Hospital Dates: Jun 1998 – May 

1999 Size of population: 180 women Other Consecutive patients undergoing surgery with masses Reference standard: Surgery Reference standard applied to all test negatives?: No, 180 patients evaluated by TVUS for adnexal mass; only 91 underwent surgery Test reliability established?: Yes Statistical tests used: ROC Se, Sp McNemar test 

Age: Mean (SD): 46.6 (14.1) Range: 16-81 Menopausal status (n [%]): Pre (< 45): 58 (63.7%) Post (> 55): 33 (36.3%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Adnexal mass undergoing surgery Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Morphology criteria of Sassone et al 

 Dis+ Dis- Tot T+ 23 19 42 

T- 2 47 49 Tot 25 66 91  Lower Upper  Value 95% CI 95% CI Se 92.0% 81.4% 100.0%Sp 71.2% 60.3% 82.1% PPV 54.8% 39.7% 69.8% NPV 95.9% 90.4% 100.0%

2) Arterial Doppler (RI) T+≤ 0.45 (in patients 

in whom arterial flow was detected) (Table 3) 

 Dis+ Dis- Tot T+ 17 1 18 

T- 6 26 32 Tot 23 27 50  Lower Upper  Value 95% CI 95% CI Se 76.0% 58.5% 93.5% Sp 95.5% 87.7% 100.0%

PPV 94.4% 83.9% 100.0%NPV 81.3% 67.7% 94.8% 

3) Venous Doppler; cutoff not described 

 Dis+ Dis- Tot T+ 12 1 13

Comme--LMP tin analy--There inconsisof Venoreportereporte--Pre-stasympt--ResulundergoQuality ReferenVerificaTest reSasonnSample StatisticBlindingDefinitiomorphoarterial 
D-42

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

Blinding: Surgeons blinded to US result Prospective studyDefinition of positive and negative on screening test: Sasonne’s scoring system (ref 20) Wall thickness (1-3) Septa (1-3) Inner wall structure (1-4) Echogenicity (1-5) Total score is sum, ranges from 4-15 T+ if score ≥ 9 

Arterial flow lowest RI ≤0.45 Venous Doppler calculated from ROC curve but no number given in text 

T- 6 13 19 

Tot 18 14 32  Lower Upper  Value 95% CI 95% CI Se 68.0% 46.4% 89.6% Sp 93.9% 81.4% 100.0%

PPV 92.3% 77.8% 100.0%NPV 68.4% 47.5% 89.3% 

4) Venous flow velocity; cutoff 10 cm/s AUC = 0.859 ± 0.06 SEM 

 Dis+ Dis- Tot T+ 17 4 21 

T- 1 10 11 Tot 18 14 32  Lower Upper  Value 95% CI 95% CI Se 94.0% 83.0% 100.0%Sp 71.0% 47.2% 94.8% 

PPV 81.0% 64.2% 97.7% NPV 90.9% 73.9% 100.0%

Alcazar, Merce, Laparte, et al., 2003 #5390 

Geographical location: Pamplona and Madrid, Spain Dates: 

Part 1 Jan 1995 – Jun 201 Part 2 Jul 2001 – Apr 2002 Size of population: Part One 665 (705 masses) Part Two 86 (90 masses) Other Part 1 retrospective analysis of ultrasound data to construct scoring system 

Age: Part 2 Mean (SD): 53.5 (11.3) Range: 20-80 Menopausal status (n [%]): Pre (< 45): 26 (30.2%) Post (> 55): 60 (69.8%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Part 1 retrospective analysis of 665 women with adnexal masses who had US in hospital during 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Sassone 

 Dis+ Dis- Tot T+ 20 7 27 

T- 11 52 63 Tot 31 59 90  Lower Upper  Value 95% CI 95% CI Se 64.5% 47.7% 81.3% Sp 88.1% 79.8% 96.4% 

PPV 74.1% 57.5% 90.6% NPV 82.5% 73.2% 91.9% 

2) DePriest 

 Dis+ Dis- Tot T+ 31 11 42 

T- 0 48 48

Comme--Stepw--Their descrip--Bordemaligna--2x2 taindividu--Pre-stasymptQuality ReferenVerificaTest reSassonFerrazzSample StatisticBlinding
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

Part 2 prospective of consecutive patients to test scoring system and compare with other ultrasound scoring systems Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Sassone – Yes DePriest – Yes Ferrazzi - ? This one - ? Statistical tests used: Multivariate logistic regression ROC curves Blinding: NR – same individual did all US – prospective part 2 Definition of positive and negative on screening test: Not described for Sassone, DePries,t or Ferrazzi (but can assume to be identical to reported in literature). Their scoring system used variables only for: Thick papillary projections, high velocity/low resistance, solid area, and central 

time frame. Part 2 – prospective analysis of women (consecutive? – NR) with adnexal masses who had surgery in time frame at hospital Exclusion criteria: NR 

Tot 31 59 90 

 Lower Upper  Value 95% CI 95% CI Se 100.0% 90.3% 100.0%Sp 81.4% 71.5% 91.3% 

PPV 73.8% 60.5% 87.1% NPV 100.0% 93.8% 100.0%

3) Ferrazzi 

 Dis+ Dis- Tot T+ 26 10 36 

T- 5 49 54 Tot 31 59 90  Lower Upper  Value 95% CI 95% CI Se 83.9% 71.0% 96.8% Sp 83.1% 73.5% 92.7% 

PPV 72.2% 57.6% 86.9% NPV 90.7% 83.0% 98.5% 

4) Current study 

 Dis+ Dis- Tot T+ 31 3 34 

T- 0 56 56 Tot 31 59 90  Lower Upper  Value 95% CI 95% CI Se 100.0% 90.3% 100.0%Sp 94.9% 89.3% 100.0%

PPV 91.2% 81.6% 100.0%NPV 100.0% 94.6% 100.0%

5) Menopause Sassone 

 Dis+ Dis- Tot T+ 17 4 21 

T- 11 30 41 Tot 28 34 62  Lower Upper 

Definitiofor curr
D-44

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

flow (unclear how this is measured). 

 Value 95% CI 95% CI Se 61.0% 42.9% 79.1% 

Sp 88.0% 77.1% 98.9% 

PPV 81.0% 64.2% 97.7% NPV 73.2% 59.6% 86.7% 

6) Menopause DePriest 

 Dis+ Dis- Tot T+ 28 6 34 

T- 0 28 28 Tot 28 34 62  Lower Upper  Value 95% CI 95% CI Se 100.0% 89.3% 100.0%Sp 82.4% 69.5% 95.2% PPV 82.4% 69.5% 95.2% NPV 100.0% 89.3% 100.0%

7) Menopause Ferrazzi 

 Dis+ Dis- Tot T+ 23 6 29 T- 5 28 33 Tot 28 34 62  Lower Upper  Value 95% CI 95% CI Se 82.0% 67.8% 96.2% Sp 82.0% 69.1% 94.9% 

PPV 79.3% 64.6% 94.1% NPV 84.8% 72.6% 97.1% 

8) Menopause current study 

 Dis+ Dis- Tot T+ 28 2 30 

T- 0 32 32 Tot 28 34 62  Lower Upper  Value 95% CI 95% CI Se 100.0% 89.3% 100.0%Sp 94.1% 86.2% 100.0%
D-45

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

PPV 93.3% 84.4% 100.0%NPV 100.0% 90.6% 100.0%

9) Premenopause Sassone 

 Dis+ Dis- Tot T+ 3 3 6 

T- 0 22 22 Tot 3 25 28  Lower Upper  Value 95% CI 95% CI Se 100.0% 0.0% 100.0%Sp 88.0% 75.3% 100.0%PPV 50.0% 10.0% 90.0% NPV 100.0% 86.4% 100.0%

10) Premenopause DePriest 

 Dis+ Dis- Tot T+ 3 5 8 T- 0 20 20 Tot 3 25 28  Lower Upper  Value 95% CI 95% CI Se 100.0% 0.0% 100.0%Sp 80.0% 64.3% 95.7% PPV 37.5% 4.0% 71.0% NPV 100.0% 85.0% 100.0%

11) Premenopause Ferrazzi 

 Dis+ Dis- Tot T+ 3 4 7 T- 0 21 21 Tot 3 25 28  Lower Upper  Value 95% CI 95% CI Se 100.0% 0.0% 100.0%Sp 84.0% 69.6% 98.4% PPV 42.9% 6.2% 79.5% NPV 100.0% 85.7% 100.0%
D-46

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

12) Premenopause current study 

 Dis+ Dis- Tot T+ 3 1 4 

T- 0 24 24 Tot 3 25 28  Lower Upper  Value 95% CI 95% CI Se 100.0% 0.0% 100.0%Sp 96.0% 88.3% 100.0%PPV 75.0% 32.6% 100.0%NPV 100.0% 87.5% 100.0%

Anandakumar, Chew, Wong, et al., 1996 #10980 

Geographical location: Singapore Dates: 1991-1993 

Size of population: 146 patients 156 tumors Case series Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: Student’s t-test Z test of proportions and indices of normality Se, Sp Blinding: Not described 

Age: Mean:For benign 35; for malignant 42.9 Range: for whole study pop 16-71 Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Women with pelvic tumors detected clinically Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR

1) Presence of flow – color imaging alone 

 Dis+ Dis- Tot T+ 26 39 65 T- 8 83 91 Tot 34 122 156  Lower Upper  Value 95% CI 95% CI Se 76.5% 62.2% 90.8% Sp 68.0% 59.7% 76.3% PPV 40.0% 28.1% 51.9% NPV 91.2% 85.4% 97.0% 

3) RI ≤ 0.66 

 Dis+ Dis- Tot T+ 24 24 48 T- 10 98 108 Tot 34 122 156  Lower Upper  Value 95% CI 95% CI Se 71.0% 55.7% 86.3% Sp 80.3% 73.2% 87.4% PPV 50.0% 35.9% 64.1% NPV 90.7% 85.3% 96.2% 

Comme--LMP tmaligna--2x2 tafor mas--No decut poin--“Color for posireprodu--Overlatumors (0.3-0.6--From Dopplesolid counable results --TVUS Quality ReferenVerificaTest reSample StatisticBlindingDefinitio+/- 
D-47

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

Definition of positive and negative on screening test: RI <= 0.66 Color flow alone = abnormal vessels “continuously fluctuating rather than pulsatile, also with mosaic pattern with yellow-green color combinations indicating turbulent flow” 

Andolf, Jorgensen, and Astedt, 1990 #1200 

Geographical location: Lund Sweden Dates: Oct 1984-Jul 

1987 Size of population: 801 screened Screening study Reference standard: Surgery or repeat US or CT within 6 months Reference standard applied to all test negatives?: No – but follow up US for all test positives who did not go to surgery Test reliability established?: Yes Statistical tests used: Not described Blinding: Not mentioned 

Age: Range: 40-70 Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): Family history: 190 (23.7%) Inclusion criteria: Women 40-70 years old who attended outpatient clinic of OB/GYN university hospital Lund, Sweden Exclusion criteria: NR; 6 scans excluded from analysis secondary to poor image quality 

Symptomatic (n [%]): 419 (52.3%) Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Using US and BME combined (both positive for test to be positive) 

 Dis+ Dis- Tot T+ 6 49 55 

T- 0 746 746 Tot 6 795 801  Lower Upper  Value 95% CI 95% CI Se 100.0% 50.0% 100.0%Sp 93.8% 92.2% 95.5% PPV 10.9% 2.7% 19.1% NPV 100.0% 99.6% 100.0%

Comme--No dean abno--No dean abno--Wome– half ccases whospitahad mo--Six wosecondmention (cancer--Unabland BM--AbdomQuality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-48

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

Definition of positive and negative on screening test: Not described 

Antonic and Rakar, 1995 #10830 

Geographical location: Ljubljana, Slovenia Dates: Jan-Jul 1993 

Size of population: 71 Prospective case series

Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: Fisher exact test Se, Sp Mann-Whitney U test Blinding: Not described but prospective Definition of positive and negative on screening test: PI [=(S-D)/M] and RI [=(S-D)/S] were calculated but test used presence or absence of colored flow without 

Age: Premenopausal women: mean 41; range 35-54 Peri 53 (52-53) Post 63 (51-82) Menopausal status (n [%]): Pre (< 45): 32 (45.1%) Peri (45-55): 4 (5.6%) Post (> 55): 29(40.8%) 6 had undergone hysterectomy (8.5%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: NR Exclusion criteria: 

NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Presence or absence of color flow in mass for all patients 

 Dis+ Dis- Tot T+ 16 28 44 

T- 2 25 27 Tot 18 53 71  Lower Upper  Value 95% CI 95% CI Se 88.9% 74.4% 100.0%Sp 47.2% 33.7% 60.6% PPV 36.4% 22.1% 50.6% NPV 92.6% 82.7% 100.0%

2) Presence or absence of color flow in mass for menopausal patients 

 Dis+ Dis- Tot T+ 13 3 16 T- 2 11 13 Tot 15 14 29  Lower Upper  Value 95% CI 95% CI Se 86.7% 69.5% 100.0%Sp 78.6% 57.1% 100.0%PPV 81.3% 62.1% 100.0%NPV 84.6% 65.0% 100.0%

3) CA-125 for all patients 

 Dis+ Dis- Tot T+ 15 4 19 T- 3 49 52 Tot 18 53 71  Lower Upper 

Comme--LMP tmaligna--No de--Good range in maligna--Did noof color --No disreliabilit--CombUS useunable Quality ReferenVerificaTest reSample StatisticBlindingDefinitiofor CA-
D-49

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

calculation CA-125 > 34 U/ml 

 Value 95% CI 95% CI Se 83.3% 66.1% 100.0%

Sp 92.5% 85.3% 99.6% PPV 78.9% 60.6% 97.3% NPV 94.2% 87.9% 100.0%

4) CA-125 for postmenopausal patients 

 Dis+ Dis- Tot T+ 13 1 14 T- 2 13 15 Tot 15 14 29  Lower Upper  Value 95% CI 95% CI Se 86.7% 69.5% 100.0%Sp 92.9% 79.4% 100.0%PPV 92.9% 79.4% 100.0%NPV 86.7% 69.5% 100.0%

Asif, Sattar, Dawood, et al., 2004 #1580 

Geographical location: Rawalpindi, Pakistan Dates: Jan 2001 – Jan 

2002 Size of population: 100 Other Consecutive preoperative patients at hospital with mass Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: CA-125 yes 

Age: Mean (SD): For malignant – 45(11) For B9 – 37(14) Menopausal status (n [%]): Pre (< 45): 56(56%) Peri (45-55): Post (> 55): 44(44%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: 100 consecutive women admitted to hospital in time frame for surgery for adnexal mass Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) CA-125 for whole study pop (> 35 U/ml) 

 Dis+ Dis- Tot T+ 45 7 52 

T- 10 38 48 Tot 55 45 100  Lower Upper  Value 95% CI 95% CI Se 82.0% 71.8% 92.2% Sp 84.0% 73.3% 94.7% 

PPV 86.5% 77.3% 95.8% NPV 79.2% 67.7% 90.7% 

2) US score (Jacobs) ≥ 1 

 Dis+ Dis- Tot T+ 53 38 91 

T- 2 7 9 Tot 55 45 100  Lower Upper  Value 95% CI 95% CI Se 96.4% 91.4% 100.0%

Comme--No tes--Unablpostmeinfo: 33 assume --Pre-stasymptQuality ReferenVerificaTest reCA125) Sample StatisticBlindingDefinitio
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

US - ? Statistical tests used: ROC Se, Sp Blinding: NR – prospective study Definition of positive and negative on screening test: CA-125 – 35U/mL US – Jacobs scoring system: cutoff not described in article 

Sp 15.6% 5.0% 26.1% PPV 58.2% 48.1% 68.4% NPV 77.8% 50.6% 100.0%

3) US score (Jacobs) ≥ 2 

 Dis+ Dis- Tot T+ 42 5 47 

T- 13 40 53 Tot 55 45 100  Lower Upper  Value 95% CI 95% CI Se 76.4% 65.1% 87.6% Sp 88.9% 79.7% 98.1% PPV 89.4% 80.5% 98.2% NPV 75.5% 63.9% 87.1% 

Balbi, Musone, Menditto, et al., 2001 #2320 

Geographical location: Naples, Italy Dates: Jan 1996-Mar 

2000 Size of population: 92 women Other Case series Reference standard: Histopathological diagnosis Reference standard applied to all test negatives?: No, 18 women with “clearly benign” masses not verified; 2 patients with “clearly malignant” disease (metastases) also excluded. Test reliability 

Age: Range: 40-80 Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: “Women with a pelvic mass originating in the ovary” Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

Not enough info to stratify by age or menopausal status 1) PE physical exam by standard protocol. Examiner was asked to predict benign or malignant. 

 Dis+ Dis- Tot T+ 20 13 33 

T- 2 37 39 Tot 22 50 72  Lower Upper  Value 95% CI 95% CI Se 90.0% 77.5% 100.0%Sp 74.0% 61.8% 86.2% 

PPV 60.6% 43.9% 77.3% NPV 94.9% 87.9% 100.0%

2) US 

 Dis+ Dis- Tot T+ 19 14 33 

T- 3 36 39 Tot 22 50 72 

Comme--20 pathat seeblinding --Physicbut exahistory mass --Althouinclude--Pre-stasymptQuality ReferenVerificaTest re125; ? fSample StatisticBlindingDefinitio
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

established?: Not for PE or CA-72-4 ? US and RI Yes for CA-125 Statistical tests used: Se, Sp Multivariate logistic analysis Blinding: NR Definition of positive and negative on screening test: PE – “palpable mass of any size ...clinically distinguishable from the gastrointestinal tract”; clinician asked to designate as benign or malignant CA-125 > 35 U/ml CA-72-4 > 3 U/ml US “multilocular solid tumor or solid tumor” from Valentin et al classification ref 19 RI < 0.4 

 Lower Upper  Value 95% CI 95% CI Se 86.0% 71.5% 100.0%

Sp 72.0% 59.6% 84.4% 

PPV 57.6% 40.7% 74.4% NPV 92.3% 83.9% 100.0%

3) CA-125 

 Dis+ Dis- Tot T+ 15 7 22 

T- 7 43 50 Tot 22 50 72  Lower Upper  Value 95% CI 95% CI Se 68.0% 48.5% 87.5% Sp 86.0% 76.4% 95.6% 

PPV 68.2% 48.7% 87.6% NPV 86.0% 76.4% 95.6% 

4) CA-72-4 > 3 U/ml 

 Dis+ Dis- Tot T+ 13 6 19 

T- 9 44 53 Tot 22 50 72  Lower Upper  Value 95% CI 95% CI Se 59.0% 38.4% 79.6% Sp 88.0% 79.0% 97.0% 

PPV 68.4% 47.5% 89.3% NPV 83.0% 72.9% 93.1% 
D-52

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommBenjapibal, Sunsaneevitayakul, Boriboonhirunsarn, et al., 2002 #2150 

Geographical location: Bangkok, Thailand Dates: Jun 2000-Sep 

2001 Size of population: 120 7 excluded for no measurable flow Other: Consecutive patients Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: Student t-test Chi-square analysis Blinding: Blinded to ultimate diagnosis, but not to other clinical factors Definition of positive and negative on screening test: PI ≤ 1.0 is positive 

(from Bourne ref 25) 

Age: Mean (SD): 41 (14) Range: 12-81 Menopausal status (n [%]): Pre (< 45): NR Peri (45-55): NR Post (> 55): “one fourth” Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Patients with suspected ovarian tumors admitted for surgery PI measured Exclusion criteria: 

PI not measurable (7) 

Symptomatic (n [%]): Abdominal pain 30.8% Detected by exam (n [%]): Palpable mass 30% Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) PI ≤ 1.0 is T+ 

 Dis+ Dis- Tot T+ 29 15 44 

T- 6 63 69 Tot 35 78 113  Lower Upper  Value 95% CI 95% CI Se 82.9% 70.4% 95.4% Sp 80.8% 72.1% 89.5% 

PPV 65.9% 51.9% 79.9% NPV 91.3% 84.7% 98.0% 

Comme--No disintent to --One ostudy cQuality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-53

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommBenjapibal, Sunsaneevitayakul, Boriboonhirunsarn, et al., 2003 #5600 

Geographical location: Bangkok, Thailand Dates: Jul 2001-Jun 

2002 Size of population: 123 3 excluded Other Patients with suspected ovarian tumor admitted for elective surgery Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: No Statistical tests used: Chi-square Blinding: NR Prospective study (but not blinded to clinical history) Definition of positive and negative on screening test: Sonographic score modified from Vera (ref 11) and Kawai (ref 12) positive > 9 (10-14) 

Age: Mean (SD): 41.5 (14.1) Range: 12-81 Menopausal status (n [%]): Pre (< 45): NR Peri (45-55): NR Post (> 55): “one fourth” Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Suspicion of ovarian mass, admitted for surgeryExclusion criteria: Non ovarian origin of tumor (n = 3; leiomyoma and parovarian cyst) 

Symptomatic (n [%]): 92% had gynecological symptoms that made them contact their physicians Detected by exam (n [%]): 8% diagnosed at routine gynecological checkup Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Sonographic pattern score ≥ 10 is T+ 

 Dis+ Dis- Tot T+ 31 9 40 

T- 4 76 80 Tot 35 85 120  Lower Upper  Value 95% CI 95% CI Se 88.6% 78.1% 99.1% Sp 89.4% 82.9% 95.9% 

PPV 77.5% 64.6% 90.4% NPV 95.0% 90.2% 99.8% 

Complete data on varying cutoffs provided (ROC curve could be constructed) 

Comme--Overlaother st--Reliabestablis--Pre-stQuality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-54

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommBerlanda, Ferrari, Mezzopane, et al., 2002 #2180 

Geographical location: Milan, Italy Dates: NR; 3-year 

period Size of population: 215 women 234 masses Other: Prospective case series Reference standard: Histology Reference standard applied to all test negatives?: Assumed yes Test reliability established?: NR Statistical tests used: Student t-tests Mann Witney U Fischers Exact McNemars Blinding: NR Definition of positive and negative on screening test: 

Ferrazzi’s morphological score (table 1)Ultrasound 1 = ≤ 3 mm; septa = none, vegetations = none; echogenicity = Sololucent 2 = > 3 mm, septa > 3 

Age: Median = 60; 47-69 (interquartile) for women with malignant masses Median = 32 and 27-43 for interquartile range Menopausal status (n [%]): Pre (< 45): 177 Peri (45-55): Post (> 55): 57 Race/ethnicity (n [%]): Italian Risk factors (n [%]): NR Inclusion criteria: Patients undergoing elective surgical treatment for adnexal masses Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: None 

1) Test characteristics based on algorithm 

 Dis+ Dis- Tot T+ 27 6 33 

T- 3 198 201 Tot 30 204 234  Lower Upper  Value 95% CI 95% CI Se 90.0% 79.3% 100.0%Sp 97.0% 94.7% 99.3% 

PPV 81.8% 68.7% 95.0% NPV 98.5% 96.8% 100.0%

2) Test characteristics based on morphological score (Ferrazzi) 

 Dis+ Dis- Tot T+ 28 24 52 

T- 2 180 182 Tot 30 204 234  Lower Upper  Value 95% CI 95% CI Se 93.0% 83.9% 100.0%Sp 88.0% 83.5% 92.5% 

PPV 53.8% 40.3% 67.4% NPV 98.9% 97.4% 100.0%

3) CA-125 > 35 U/ml 

 Dis+ Dis- Tot T+ 22 1 23 

T- 6 23 29 Tot 28 24 52  Lower Upper  Value 95% CI 95% CI Se 78.6% 63.4% 93.8% Sp 95.8% 87.8% 100.0%PPV 95.7% 87.3% 100.0%NPV 79.3% 64.6% 94.1% 

4) RI ≤ 0.6 

Comme--Presefor pre other in2x2. --NOTEwomen--RI ≤ 0--Masseteratomregardle--Pre-stasymptQuality ReferenVerificaTest reSample StatisticBlindingDefinitio + 
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

mm, low echogenicity 3 = septa > 3 mm, 4 = irregular, mostly solid; vegetations ≤ 3, 

with echogenic areas 5 = irregular, nonapplicable, > 3mm, with heterogeneous echogenic areas, solid Score ≥ 9 considered 

suspicious for malignancy Additional factors considered Mean diameter ≥ 10 cm; immobility, bilaterality, presence of ascites, resistance index < 0.6 and serum CA-125 > 35 IUml Note: additional factors used to develop an algorithm. Algorithm compared to morphological score. Low risk – masses with score < 9 mm and typical cystic teratomas Moderate risk ≥ 9 suspicious for malignancy, absence of any one of the additional criteria defined above High risk ≥ 9 and any of the above factors. 

 Dis+ Dis- Tot T+ 19 6 25 

T- 9 18 27 Tot 28 24 52  Lower Upper  Value 95% CI 95% CI Se 67.9% 50.6% 85.2% Sp 75.0% 57.7% 92.3% PPV 76.0% 59.3% 92.7% NPV 66.7% 48.9% 84.4% 
D-56

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommBromley, Goodman, and Benacerraf, 1994 #4630 

Geographical location: Boston, MA Dates: Mar 1992-Apr 

1993 Size of population: 33 Other Prospective series Reference standard: Pathology Reference standard applied to all test negatives?: Yes Test reliability established?: NR Statistical tests used: None stated Se, Sp, PPV, NPV Blinding: NR Definition of positive and negative on screening test: Sonography Clear cyst < 3 cm -1 Clear cyst ≥ 3 cm – 2 

Cyst with slight irregular wall on one side 3 Cyst with uniform lowlevel echoes or a single thin septation - 4 Solid ovarian enlargement; cyst with irregular borders, 

Age: NR Menopausal status (n [%]): Post (> 55): 100% Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Pelvic masses diagnosed by sonography and histopathologic verification of disease Consecutive cases Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: Scanned transabdominally and transvaginally. 

1) Scoring system 

 Dis+ Dis- Tot T+ 11 10 21 

T- 1 11 12 Tot 12 21 33  Lower Upper  Value 95% CI 95% CI Se 91.0% 74.8% 100.0%Sp 52.0% 30.6% 73.4% 

PPV 52.4% 31.0% 73.7% NPV 91.7% 76.0% 100.0%

2) Resistance index using 0.6 

 Dis+ Dis- Tot T+ 8 4 12 

T- 4 17 21 Tot 12 21 33  Lower Upper  Value 95% CI 95% CI Se 66.0% 39.2% 92.8% Sp 81.0% 64.2% 97.8% 

PPV 66.7% 40.0% 93.3% NPV 81.0% 64.2% 97.7% 

Comme--Uncle--Bordegroup -- 33 soseems women--Pre-stasymptQuality ReferenVerificaTest reSample StatisticBlindingDefinitio + 
D-57

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

nonspecific ovarian masses 5-6 Multiple septations and nodular cystic mass 7-9 7 = less nodularity; 9 = more nodules and septations Same as 7-9 with ascites 10 Doppler Resistance index = (systolic peak – diastolic trough)/ systolic peak Lowest resistance index used RI < 0.6 

Brown, Doubilet, Miller, et al., 1998 #3350 

Geographical location: Boston, MA Dates: Jul 1991-Jul 

1996 Size of population: 194 Other Consecutive patients Reference standard: Histopathology Reference standard applied to all test negatives?: No (but negatives without surgery had followup US that demonstrated resolution) Test reliability established?: Yes 

Age: Mean (SD): 39.9 (12.7) Range: 16-78 Menopausal status (n [%]): Pre (< 45): 135 (69.6%) Post (> 55): 38 (19.6%) don’t add to 100% because 21 (10.8%) had hysterectomy Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: All adnexal masses scanned at the institution where both gray-scale and Doppler sonography had been done and Exclusion criteria: 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR Malignancy score based on logistic regression model derived from gray-scale and Doppler sonography features Solid component  None (0)  Hyperechoic (13)  non-hyperechoic (394) 

1) Malignancy score – cutoff 453 AUC 0.98 ± 0.01 

 Dis+ Dis- Tot T+ 26 13 39 

T- 2 170 172 Tot 28 183 211  Lower Upper  Value 95% CI 95% CI Se 93.0% 83.5% 100.0%Sp 93.0% 89.3% 96.7% 

PPV 66.7% 51.9% 81.5% NPV 98.8% 97.2% 100.0%

2) Malignancy score – cutoff 433 AUC 0.98 ± 0.01 

 Dis+ Dis- Tot T+ 28 26 54 

T- 0 157 157 Tot 28 183 211  Lower Upper 

Value 95% CI 95% CI

Comme--No mo--Pre-stasymptQuality ReferenVerificaTest reSample StatisticBlindingDefinitiovariableindepen
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

Statistical tests used: Mann-Whitney U test Fisher exact test Chi-square Stepwise logistic regression ROC curves Blinding: Yes US done prospectively, scale done after by blinded individual Definition of positive and negative on screening test: See column 3 

Pregnant masses Premenopausal patients > 10 days after LMP Simple cysts < 2 cm in premenopausal women Extraovarian masses on US 

Fluid component (anechoic, echogenic, none) Septations  Thin (0)  Thick (22)  None (38) Wall (thin, thick, none) Free fluid  Present (38)  Absent (0) Bilateral masses (yes, no) Size, average (cm) Size, maximum (cm) Flow location  Central (37)  Peripheral only (1)  None detected (0) 

Se 100.0% 89.3% 100.0%

Sp 85.8% 80.7% 90.9% PPV 51.9% 38.5% 65.2% NPV 100.0% 98.1% 100.0%

Buckshee, Temsu, Bhatla, et al., 1998 #710 

Geographical location: New Delhi, India Dates: May 1995-Apr 

1997 Size of population: 34 individuals 36 tumors Other Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: No for PE Yes for US 

Age: 20-30: n = 10 31-40: n = 13 41-50: n = 6 > 50: n = 5 Menopausal status (n [%]): Pre (< 40): 23 (67.6%) Peri (41-50): 6 (17.6) Post (> 50): 5 (14.7%) Race/ethnicity (n [%]): NR Risk factors (n [%]): Family history: 1 (2.9%) Inclusion criteria: Women with presumed adnexal mass going to surgery Exclusion criteria: Women with proven 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) PE (diagnosed as malignant = T+) 

 Dis+ Dis- Tot T+ 7 3 10 

T- 2 24 26 Tot 9 27 36  Lower Upper  Value 95% CI 95% CI Se 77.8% 50.6% 100.0%Sp 88.9% 77.1% 100.0%

PPV 70.0% 41.6% 98.4% NPV 92.3% 82.1% 100.0%

2) TVUS score (≥ 9 indicates T+) Sassone 

et al. 

 Dis+ Dis- Tot T+ 9 4 13 

T- 0 23 23 Tot 9 27 36  Lower Upper 

Value 95% CI 95% CI

Comme--Unclegiven n--Did bl--This smeasur--Pre-stasymptQuality ReferenVerificaTest reSample StatisticBlindingDefinitio
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

Statistical tests used: Fisher’s exact test Se, Sp Blinding: No but prospective enrollment PE was blinded to US result Definition of positive and negative on screening test: PE – clinical impression of benign or malignant Gray-scale sonography – Sassone criteria ≥ 9 

malignant PI < 1 malignant 

diagnosis of malignancy/metastatic disease on ultrasound or CT 

Se 100.0% 66.7% 100.0%

Sp 85.2% 71.8% 98.6% PPV 69.2% 44.1% 94.3% NPV 100.0% 87.0% 100.0%

3) Pulsatility Index (< 1 indicates T+) 

 Dis+ Dis- Tot T+ 6 1 7 T- 3 26 29 Tot 9 27 36  Lower Upper  Value 95% CI 95% CI Se 66.7% 35.9% 97.5% Sp 96.3% 89.2% 100.0%PPV 85.7% 59.8% 100.0%NPV 89.7% 78.6% 100.0%

Buist, Golding, Burger, et al., 1994 #960 

Geographical location: The Netherlands Dates: Nov 1988-Sep 

1992 Size of population: 64 Other Prospective series Reference standard: Pathology Reference standard applied to all test negatives?: 

Yes

Test reliability established?: Yes Statistical tests used: 

Age: Median: 60 Range: 24-84 Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Clinically suspected of having primary or recurrent cancer Exclusion criteria: Declined participation, contraindications for one of the diagnostic methods or organizational reasons prevented all methods 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

Data are for primary cancer Recurrent presented but not included here. 1) CT – reviewer a 

 Dis+ Dis- Tot T+ 26 10 36 

T- 1 8 9 Tot 27 18 45  Lower Upper  Value 95% CI 95% CI Se 96.0% 88.6% 100.0%Sp 44.0% 21.1% 66.9% 

PPV 72.2% 57.6% 86.9% NPV 88.9% 68.4% 100.0%

2) CT – reviewer b 

 Dis+ Dis- Tot T+ 24 3 27 

T- 3 15 18 Tot 27 18 45 

Comme--PE by --Populhaving CA”-likeunblind--45 witr/o recuprimary --Imagicancer test --No CA--No PE --Pre-stasymptQuality ReferenVerificaTest reSample intervalStatisticBlinding
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

ROC curves Fisher’s exact Chi-square Se, Sp Blinding: Yes Definition of positive and negative on screening test: NR 

being performed before surgery 

 Lower Upper  Value 95% CI 95% CI Se 89.0% 77.2% 100.0%

Sp 83.0% 65.6% 100.0%

PPV 88.9% 77.0% 100.0%NPV 83.3% 66.1% 100.0%

3) MRI – reviewer a 

 Dis+ Dis- Tot T+ 26 12 38 

T- 1 6 7 Tot 27 18 45  Lower Upper  Value 95% CI 95% CI Se 96.0% 88.6% 100.0%Sp 33.0% 11.3% 54.7% 

PPV 68.4% 53.6% 83.2% NPV 85.7% 59.8% 100.0%

4) MRI – reviewer b 

 Dis+ Dis- Tot T+ 26 1 27 

T- 1 17 18 Tot 27 18 45  Lower Upper  Value 95% CI 95% CI Se 96.0% 88.6% 100.0%Sp 94.0% 83.0% 100.0%

PPV 96.3% 89.2% 100.0%NPV 94.4% 83.9% 100.0%

5) US 

 Dis+ Dis- Tot T+ 24 10 34 

T- 3 8 11 Tot 27 18 45  Lower Upper  Value 95% CI 95% CI Se 89.0% 77.2% 100.0%

examinsuspecDefinitio- 
D-61

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

Sp 44.0% 21.1% 66.9% 

PPV 70.6% 55.3% 85.9% NPV 72.7% 46.4% 99.0% 

6) Physical Exam 

 Dis+ Dis- Tot T+ 26 1 27 

T- 1 17 18 Tot 27 18 45  Lower Upper  Value 95% CI 95% CI Se 96.0% 88.6% 100.0%Sp 94.0% 83.0% 100.0%

PPV 96.3% 89.2% 100.0%NPV 94.4% 83.9% 100.0%

7) CA-125 

 Dis+ Dis- Tot T+ 22 6 28 

T- 5 12 17 Tot 27 18 45  Lower Upper  Value 95% CI 95% CI Se 81.0% 66.2% 95.8% Sp 67.0% 45.3% 88.7% 

PPV 78.6% 63.4% 93.8% NPV 70.6% 48.9% 92.2% 

Kappa for inter-observer reliability: CT = 0.28 MRI = 0.41 
D-62

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommBuy, Ghossain, Hugol, et al., 1996 #4030 

Geographical location: Paris, France Dates: Jan 1993 – Dec 

1994 Size of population: 160 patients 115 met inclusion criteria Other Prospective series Reference standard: Pathology Reference standard applied to all test negatives?: Yes Test reliability established?: No Statistical tests used: Mann Witney McNemar Blinding: NR Definition of positive and negative on screening test: Sonography Borderline or malignant Echogenic structure against the wall of the cyst present; large irregular homogeneous or heterogeneous echogenic structure Irregular thickened (3 mm) wall or septum 

Age: Benign Mean: 40 Range: 22-73 Menopausal = 28 Borderline 47 and 50 years Both premenopausal Malignant 57 mean; 22-84 Menopausal =15 Menopausal status (n [%]): Pre (< 45): 72 (63%) Post (> 55): 43 (37%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Adnexal mass suspected by physical exam or discovered during previous sonography Only patients who had laparoscopy Laparotomy (not laproscopy) included. Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Conventional sonography – indeterminate masses classified as malignant 

 Dis+ Dis- Tot T+ 22 16 38 

T- 3 74 77 Tot 25 90 115  Lower Upper  Value 95% CI 95% CI Se 88.0% 75.3% 100.0%Sp 82.0% 74.1% 89.9% 

PPV 57.9% 42.2% 73.6% NPV 96.1% 91.8% 100.0%

2) Color Doppler and sonography 

 Dis+ Dis- Tot T+ 22 3 25 

T- 3 87 90 Tot 25 90 115  Lower Upper  Value 95% CI 95% CI Se 88.0% 75.3% 100.0%Sp 97.0% 93.5% 100.0%

PPV 88.0% 75.3% 100.0%NPV 96.7% 93.0% 100.0%

3) Resistive Index 

 Dis+ Dis- Tot T+ 5 3 8 

T- 21 87 108 Tot 25 90 116  Lower Upper  Value 95% CI 95% CI Se 18.0% 2.9% 33.1% Sp 97.0% 93.5% 100.0%

PPV 62.5% 29.0% 96.0% NPV 80.6% 73.1% 88.0% 

Comme--Unabl--Meno--No scdescrip--Bordegrouped --Pre-stasymptQuality ReferenVerificaTest reSample StatisticBlindingDefinitio + 
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

present. Benign – mass did not present with any of the findings of malignant tumors, or pattern typical of a benign ovarian mass. Method 2. Morphology + color Doppler Presence of color flow in echogenic portion charac. As malignant - considered malignant Absence of color flow – considered benign If mass classified as benign using morphology then malignant if color flow in a regular wall, regular septum or regular solid mass – benign. No color flow – benign. Method 3. Spectral Doppler analysis Absence of arterial flow – considered benign. Measured RI, PI and PSV (no definition provided). Lowest values retained. Mass malignant if Resistive Index ≤ 0.4; Pulsatility Index ≤ 1 and Peak systolic velocity ≥

15 cm/sec. 

4) Pulsatility Index 

 Dis+ Dis- Tot T+ 18 3 21 

T- 7 87 94 Tot 25 90 115  Lower Upper  Value 95% CI 95% CI Se 71.0% 53.2% 88.8% Sp 97.0% 93.5% 100.0%

PPV 85.7% 70.7% 100.0%NPV 92.6% 87.2% 97.9% 

5) Peak systolic velocity 

 Dis+ Dis- Tot T+ 12 3 15 

T- 13 87 100 Tot 25 90 115  Lower Upper  Value 95% CI 95% CI Se 47.0% 27.4% 66.6% Sp 97.0% 93.5% 100.0%

PPV 80.0% 59.8% 100.0%NPV 87.0% 80.4% 93.6% 
D-64

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommCanis, Pouly, Wattiez, et al., 1997 #3710 

Geographical location: Clermont-Ferrand, France Dates: Jan 1992-Dec 

1994 Size of population: 558 Other Case series Reference standard: Surgery Reference standard applied to all test negatives?: Yes Test reliability established?: No Statistical tests used: Se, Sp Blinding: No Definition of positive and negative on screening test: Ultrasound “suspicious” if solid, mixed, mixed with calcified area, vegetations, cyst wall ≥ 3 

mm, thick septa ≥ 3 mm, 

> 3 septae, multicystic, or ascites”; otherwise considered benign 

Age: NR Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: NR Exclusion criteria: 

Masses discovered at surgery 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Ultrasound results; low malignant potential = benign 

 Dis+ Dis- Tot T+ 29 218 247 

T- 1 310 311 Tot 30 528 558  Lower Upper  Value 95% CI 95% CI Se 96.7% 90.2% 100.0%Sp 58.7% 54.5% 62.9% PPV 11.7% 7.7% 15.8% NPV 99.7% 99.0% 100.0%

2) Low malignant potential = cancer 

 Dis+ Dis- Tot T+ 43 204 247 T- 2 309 311 Tot 45 513 558  Lower Upper  Value 95% CI 95% CI Se 95.6% 89.5% 100.0%Sp 60.2% 56.0% 64.5% PPV 17.4% 12.7% 22.1% NPV 99.4% 98.5% 100.0%

Comme--Clinica--Other given --Not stabdomiQuality ReferenVerificaTest reSample StatisticBlindingDefinitio + 
D-65

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommCarter, Iles, Neven, et al., 1993 #6370 

Geographical location: England Dates: NR 

Size of population: 152 Study type NR Reference standard: Histology Reference standard applied to all test negatives?: Yes Test reliability established?: For CA-125 Statistical tests used: None Blinding: NR Definition of positive and negative on screening test:  “95% of normal blood samples have a CA-125 level < 37.2 u/ml” but not necessarily used 

Age: NR Menopausal status (n [%]): Pre (< 45): 86 Post (> 55): 66 Race/ethnicity (n [%]): NR Risk factors (n [%]): None Inclusion criteria: Presentation with pelvic mass Exclusion criteria: NR 

Not specified Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) CA – 125 Not enough data provided to stratify table by menopausal status 

 Dis+ Dis- Tot T+ 77 1 78 

T- 10 64 74 Tot 87 65 152  Lower Upper  Value 95% CI 95% CI Se 88.5% 81.8% 95.2% Sp 98.5% 95.5% 100.0%

PPV 98.7% 96.2% 100.0%NPV 86.5% 78.7% 94.3% 

Comme----Pre-vs. asy--Uncle--Recursample --CA-12(35? 37Quality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-66

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommCarter, Lau, Fowler, et al., 1995 #4240 

Geographical location: Minneapolis, MN Dates: NR 

Size of population: 123 women Other Consecutive Reference standard: Histopathology or 12 month followup Reference standard applied to all test negatives?: No, but those without operative intervention were followed by US for 12 months Test reliability established?: Yes Statistical tests used: Se, Sp Chi-squared ROC Blinding: NR but prospective study (but not blinded to clinical history) Definition of positive and negative on screening test: Calculated from ROC curves Best P I< 1.0 RI < 0.4 

Age: Mean: 48.3 Menopausal status (n [%]): Pre (< 45): 72 (58.5%) Post (> 55): 51(41.5%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Women with suspected adnexal mass presenting to University of Minn women’s hospital Exclusion criteria: NR (everyone else) 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) PI < 1.0 (AUC = 0.732 ± 0.069) 

 Dis+ Dis- Tot T+ 13 21 34 

T- 10 79 89 Tot 23 100 123  Lower Upper  Value 95% CI 95% CI Se 57.0% 36.8% 77.2% Sp 79.0% 71.0% 87.0% 

PPV 38.2% 21.9% 54.6% NPV 88.8% 82.2% 95.3% 

2) RI < 0.4 (AUC = 0.684 ± 0.068) 

 Dis+ Dis- Tot T+ 5 4 9 

T- 18 96 114 Tot 23 100 123  Lower Upper  Value 95% CI 95% CI Se 22.0% 5.1% 38.9% Sp 96.0% 92.2% 99.8% 

PPV 55.6% 23.1% 88.0% NPV 84.2% 77.5% 90.9% 

2x2 table also calculable for PI at cutoffs of 0.6, 0.8 and 1.4 RI at cutoffs of 0.6, 0.8 and 1.0 

Comme--No res--Pre-stasymptQuality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-67

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommCaruso, Caforio, Testa, et al., 1996 #3810 

Geographical location: Rome, Italy Dates: NR 

Size of population: 122 Other Consecutive patients with diagnosis of adnexal mass scheduled for surgery Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Sasonne’s [3] – yes DePriest {1} - ? Valentine [2] - ? “Vascular score” - NO Statistical tests used: Student’s t test Fisher’s exact test Blinding: NR but US prior to surgery Definition of positive and negative on screening test: Sasonne and DePriest – not described Valentine positive ≥ 3 (where 1 = unilocular cyst, 2 = multilocular 

Age: Mean (SD): 38.4 (16.5) Menopausal status (n [%]): Pre: 88 (70.5%) Post: 36 (29.5%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: 122 consecutive patients with diagnosis of adnexal mass scheduled to undergo surgery at the study hospital Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Sasonne’s criteria 

 Dis+ Dis- Tot T+ 21 27 48 

T- 0 74 74 Tot 21 101 122  Lower Upper  Value 95% CI 95% CI Se 100.0% 85.7% 100.0%Sp 73.3% 64.6% 81.9% PPV 43.8% 29.7% 57.8% NPV 100.0% 95.9% 100.0%

2) DePriest Score 

 Dis+ Dis- Tot T+ 21 31 52 T- 0 70 70 Tot 21 101 122  Lower Upper  Value 95% CI 95% CI Se 100.0% 85.7% 100.0%Sp 69.3% 60.3% 78.3% PPV 40.4% 27.0% 53.7% NPV 100.0% 95.7% 100.0%

3) Valentin score 

 Dis+ Dis- Tot T+ 21 39 60 T- 0 62 62 Tot 21 101 122  Lower Upper  Value 95% CI 95% CI Se 100.0% 85.7% 100.0%Sp 61.4% 51.9% 70.9% PPV 35.0% 22.9% 47.1% NPV 100.0% 95.2% 100.0%

4) Vascular score 

Comme--Aside (which “arbitrascoring --Their mostly save R--Menoto stratierror (“twomen lesions respect--Reporcriteria preciseQuality ReferenVerificaTest reSasson(referenof reliab+ for “vCV was the sco(+/-%) Sample StatisticBlindingprospecsurgery Definitiofor ValeOthers 
D-68

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

cyst, 3 = unilocular solid cyst, 4 = multilocular solid tumor, 5 = solid tumor) “Vascular score” – [table1] ≥ 5 is positive (where 1 for vessels present, vascular location 1 for pericystic 2 for in solid part, 2 for randomly dispersed vessels, 2 for “smooth waveform”, 2 for lowest RI < 0.430 

 Dis+ Dis- Tot T+ 21 8 29 

T- 0 93 93 Tot 21 101 122  Lower Upper  Value 95% CI 95% CI Se 100.0% 85.7% 100.0%Sp 92.1% 86.8% 97.3% PPV 72.4% 56.1% 88.7% NPV 100.0% 96.8% 100.0%

5) Vascular score excluding the 6 patients with a score .+5 studied in luteal phase 

 Dis+ Dis- Tot T+ 18 4 22 T- 0 93 93 Tot 18 97 115  Lower Upper  Value 95% CI 95% CI Se 100.0% 83.3% 100.0%Sp 96.0% 92.1% 99.9% 

PPV 81.8% 65.7% 97.9% NPV 100.0% 96.8% 100.0%
D-69

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommChalas, Welshinger, Engellener, et al., 1992 #5100 

Geographical location: Stony Brook, NY Dates: May 1980-Apr 

1990 Size of population: 288 (47 excluded) Other Series of patients at single center with pelvic mass who were operated on Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes for CA-125 No for platelet count Statistical tests used: Chi-square Se, Sp Blinding: NR But prospective Definition of positive and negative on screening test: CA-125 > 35U/mL Platelets > 400,000/pico L 

Age: NR Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Women with pelvic mass diagnosis who underwent surgery in hospital during time frame Exclusion criteria: 47 excluded because 1) lack of preop platelet count 2) underlying condition associated with thrombocytosis 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) CA-125 > 35 

 Dis+ Dis- Tot T+ 60 8 68 

T- 14 48 62 Tot 74 56 130  Lower Upper  Value 95% CI 95% CI Se 81.1% 72.2% 90.0% Sp 85.7% 76.5% 94.9% PPV 88.2% 80.6% 95.9% NPV 77.4% 67.0% 87.8% 

2) Platelets > 400,000/microliter 

 Dis+ Dis- Tot T+ 78 16 94 T- 61 86 147 Tot 139 102 241  Lower Upper  Value 95% CI 95% CI Se 56.1% 47.9% 64.4% Sp 84.3% 77.3% 91.4% PPV 83.0% 75.4% 90.6% NPV 58.5% 50.5% 66.5% 

Comme--LMP tmaligna--Althou125 and other ncannot CA-125 83% < thrombo60%; S--Se, Sin table calculat--ClinicaQuality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-70

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommChen, Schwartz, and Li, 1990 #5330 

Geographical location: China Dates: NR 

Size of population: 188 Other Convenience sample Reference standard: Histology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: Regression analyses Chi-square Blinding: NR Definition of positive and negative on screening test: CA-125 (serum) > 65 U/ml considered positive 

Age: 20-42 for healthy blood donors – age not provided for 92 patients with benign pelvic masses and 41 patients with malignant masses of whom 16 had ovarian cancer Menopausal status 

(n [%]): 

NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: 55 health female blood donors 92 patients with benign pelvic masses 41 patients with malignant masses Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) CA-125 – serum (among the 92 women with benign masses and 16 patients with ovarian cancer) 

 Dis+ Dis- Tot T+ 15 37 52 

T- 1 55 56 Tot 16 92 108  Lower Upper  Value 95% CI 95% CI Se 93.8% 82.0% 100.0%Sp 59.8% 49.8% 69.8% 

PPV 28.8% 16.5% 41.2% NPV 98.2% 94.7% 100.0%

Comme--Knew diagnosthis imp--CA-12--Borde--Not pr--ClinicaQuality ReferenVerificaTest reSample Only 8 StatisticBlindingDefinitio
D-71

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommChen, Schwartz, Li, et al., 1988 #6870 

Geographical location: Changsha, China Dates: Sep 1985 – Aug 

1986 Size of population: 211 preoperative 44 normal patients Other“Screening” for “normal” patients (but no follow up described) For 211 – diagnosis of mass undergoing surgery at the hospital Reference standard: Histopathology Reference standard applied to all test negatives?: Not to “normal” comparison group but to all of 211 preop patients. Test reliability established?: Yes Statistical tests used: Se, Sp Blinding: NR but testing preceded surgery Definition of positive and negative on screening test: CA-125 > 35 (see comments) 

Age: Mean (SD): Benign masses 38 (11) Malignant 43 (5) Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: “Normal” – normal physical exam and LFTs 211 – “pelvic mass” who had surgery Exclusion criteria: 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) CA-125 for 211 operative patients (> 35 U/ml = T+) 

 Dis+ Dis- Tot T+ 48 61 109 

T- 10 92 102 Tot 58 153 211  Lower Upper  Value 95% CI 95% CI Se 82.8% 73.1% 92.5% Sp 60.1% 52.3% 67.9% 

PPV 44.0% 34.7% 53.4% NPV 90.2% 84.4% 96.0% 

2) CA-125 (> 35 U/ml = T+) limited to patients with epithelial ovarian cancer (excludes non-ovarian malignancies) 

 Dis+ Dis- Tot T+ 30 61 91 

T- 0 92 92 Tot 30 153 183  Lower Upper  Value 95% CI 95% CI Se 100.0% 90.0% 100.0%Sp 60.1% 52.3% 67.9% 

PPV 33.0% 23.3% 42.6% NPV 100.0% 96.7% 100.0%

2x2 tables also provided for cutoffs of > 65 U/ml and > 194 U/ml 

Comme--No folgroup (> 35) thtable --Bordemaligna--No dechosen --Most aabnorm--This sexcludifrom the Quality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-72

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommChou, Chang, Yao, et al., 1994 #10930 

Geographical location: Taiwan, China Dates: Jan 1991 – Feb 

1993 Size of population: 108 Case Series Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: Se, Sp Blinding: NR Definition of positive and negative on screening test: RI > 0.5 CA-125 > 35U/ml 

Age: Mean: 38 Range: 11-85 Menopausal status (n [%]): Pre (< 45): 89 (82.4%) Post (> 55): 19 (17.6%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Scheduled for surgery in time frame for mass Exclusion criteria: 6 excluded : 3 with ovarian CA, 1 with borderline tumor, and 2 with chronic tubal pregnancy 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) RI < 0.5 

 Dis+ Dis- Tot T+ 22 7 29 

T- 3 76 79 Tot 25 83 108  Lower Upper  Value 95% CI 95% CI Se 88.0% 75.3% 100.0%Sp 92.0% 86.2% 97.8% 

PPV 75.9% 60.3% 91.4% NPV 96.2% 92.0% 100.0%

2) CA-125 > 35U/ml 

 Dis+ Dis- Tot T+ 23 21 44 

T- 2 62 64 Tot 25 83 108  Lower Upper  Value 95% CI 95% CI Se 92.0% 81.4% 100.0%Sp 75.0% 65.7% 84.3% 

PPV 52.3% 37.5% 67.0% NPV 96.9% 92.6% 100.0%

3) Combined CA-125 and RI 

 Dis+ Dis- Tot T+ 25 2 27 

T- 0 81 81 Tot 25 83 108  Lower Upper  Value 95% CI 95% CI Se 100.0% 88.0% 100.0%Sp 97.0% 93.3% 100.0%

PPV 92.6% 82.7% 100.0%NPV 100.0% 96.3% 100.0%

Comme--5 patie--Uncleexcludeof ovarisurgery--Clinica--Mostly used fosexual many thQuality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-73

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommCohen, Escobar, Scharm, et al., 2001 #2460 

Geographical location: Chicago, IL Dates: Apr 1999-Jun 

2000 Size of population: 71 women Other Women referred for surgery at the same hospital Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: No – see comments Statistical tests used: Se, Sp PPV, NPV Blinding: 

No but US preoperativeDefinition of positive and negative on screening test: “Any multiloculated, complex, or solid mass in which the echo architecture was not highly suggestive of benign histology was categorized as malignant” For 3D Doppler “masses 

Age: Mean (SD):  Pre - 32  Post - 59 Range: 22-80 Menopausal status (n [%]): Pre: 40 Post: 31 Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Known “complex” pelvic mass referred for preoperative US Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) 2D TVUS 

 Dis+ Dis- Tot T+ 14 26 40 

T- 0 31 31 Tot 14 57 71  Lower Upper  Value 95% CI 95% CI Se 100.0% 78.6% 100.0%Sp 54.0% 41.1% 66.9% 

PPV 35.0% 20.2% 49.8% NPV 100.0% 90.3% 100.0%

2) 2D plus 3D TVUS 

 Dis+ Dis- Tot T+ 14 14 28 

T- 0 43 43 Tot 14 57 71  Lower Upper  Value 95% CI 95% CI Se 100.0% 78.6% 100.0%Sp 75.0% 63.8% 86.2% 

PPV 50.0% 31.5% 68.5% NPV 100.0% 93.0% 100.0%

Comme--Very pconstituquestio--Doppl2D modstudy is and no --No uscriteria, --No disobservepoor de--1 bordcolon cmalignaQuality ReferenVerificaTest reSample StatisticBlindingDefinitiopoor de
D-74

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

with central vascular flow, vascular flow with in excrescences, or flow within septations were graded malignant” based on modified system by Guerriero (ref 9) 

Davies, Jacobs, Woolas, et al., 1993 #4720 

Geographical location: London Dates: NR 

Size of population: 124 Other Case series - Retrospective review of consecutive analysis of women with diagnosis of mass admitted to hospital for surgery Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: RMI Se, Sp Chi-square Students t test Mann-Whitney U test Blinding: NR 

Age: NR Menopausal status (n [%]): Pre (< 45): 86 (69.4%) Post (> 55): 38 (30.6%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Consecutive women admitted to hospital for surgery in time frame Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) CA-125 > 30 U/mL 

 Dis+ Dis- Tot T+ 28 22 50 

T- 9 65 74 Tot 37 87 124  Lower Upper  Value 95% CI 95% CI Se 76.0% 62.2% 89.8% Sp 75.0% 65.9% 84.1% 

PPV 56.0% 42.2% 69.8% NPV 87.8% 80.4% 95.3% 

2) CA-125 > 50U/mL 

 Dis+ Dis- Tot T+ 26 13 39 

T- 11 74 85 Tot 37 87 124  Lower Upper  Value 95% CI 95% CI Se 70.0% 55.2% 84.8% Sp 85.0% 77.5% 92.5% 

PPV 66.7% 51.9% 81.5% NPV 87.1% 79.9% 94.2% 

3) US > 1 

 Dis+ Dis- Tot T+ 37 62 99 

T- 0 25 25 Tot 37 87 124  Lower Upper 

Comme--Standexamin--US sc(Jacobscontext--ClinicaQuality ReferenVerificaTest rediscussSample StatisticBlindingDefinitio
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

Definition of positive and negative on screening test: NR – because test of RMI, various cutoff values analyzed 

 Value 95% CI 95% CI Se 100.0% 91.9% 100.0%

Sp 29.0% 19.5% 38.5% 

PPV 37.4% 27.8% 46.9% NPV 100.0% 88.0% 100.0%

4) US 3 

 Dis+ Dis- Tot T+ 32 23 55 

T- 5 64 69 Tot 37 87 124  Lower Upper  Value 95% CI 95% CI Se 87.0% 76.2% 97.8% Sp 74.0% 64.8% 83.2% 

PPV 58.2% 45.1% 71.2% NPV 92.8% 86.6% 98.9% 

5) Menopausal status alone 

 Dis+ Dis- Tot T+ 32 36 68 

T- 5 51 56 Tot 37 87 124  Lower Upper  Value 95% CI 95% CI Se 87.0% 76.2% 97.8% Sp 59.0% 48.7% 69.3% 

PPV 47.1% 35.2% 58.9% NPV 91.1% 83.6% 98.5% 
D-76

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommDePriest, Gallion, Pavlik, et al., 1997 #3650 

Geographical location: Kentucky Dates: Dec 1987-Dec 

1993 Size of population: 6470 Screening study Reference standard: Histology and follow up Reference standard applied to all test negatives?: Followup applied Test reliability established?: NR Statistical tests used: Fischers exact test Blinding: NR Definition of positive and negative on screening test: Ultrasound Ovarian volume >10 cm3

for postmenopausal women and > 20 cm3 for 

premenopausal Cystic tumor with internal papillary or complex projections into its lumen was considered abnormal. Used an algorithm for disease detection 

Age: Mean: 58 Range: 30-92 Menopausal status (n [%]): Numbers of women by menopausal status not specified although used as an entry criterion. Race/ethnicity (n [%]): NR Risk factors (n [%]): Family history: Ovarian cancer = 1597 (24%) Breast cancer = 1976 (30%) Colon cancer = 990 (15%)Inclusion criteria: Asymptomatic postmenopausal women > 50 years of age Asymptomatic women > 30 years of age with a documented history of ovarian cancer in at least one primary or secondary relative. Exclusion criteria: Known ovarian tumor or personal history of ovarian cancer. 

Symptomatic (n [%]): 0 (0%) Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) TVUS 

 Dis+ Dis- Tot T+ 6 84 90 

T- 1 6379 6380 Tot 7 6463 6470  Lower Upper  Value 95% CI 95% CI Se 85.7% 59.8% 100.0%Sp 98.7% 98.4% 99.0% PPV 6.7% 1.5% 11.8% NPV 100.0% 100.0% 100.0%

2) For operative cases with morphology index < 4 

 Dis+ Dis- Tot T+ 7 34 41 T- 0 49 49 Tot 7 83 90  Lower Upper  Value 95% CI 95% CI Se 100.0% 57.1% 100.0%Sp 59.0% 48.5% 69.6% PPV 17.1% 5.6% 28.6% NPV 100.0% 93.9% 100.0%

Comme--Data nmenopa--None ovarian drawn h--DePri90 oper--% follodescribQuality ReferenVerificaTest reSample StatisticBlindingDefinitio + 
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

If TVUS abnormal, repeat 4-6 weeks. If that’s abnormal used additional tests and then surgery. If normal repeat TVUS in one year. If TVUS initially normal, repeat in one year. 

DePriest, Shenson, Fried, et al., 1993 #6390 

Geographical location: Lexington, Kentucky USA University Hospital Dates: Jan 1987 – Jan 

1992 Size of population: 121 Other Case series Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: No Statistical tests used: T test for means Chi-square and Fisher’s exact test for proportions Blinding: NR (but prospective) Definition of positive 

Age: Mean (SD): pre 30.9 Post 55.9 Range: pre 3-47 Post 44-74 Menopausal status (n [%]): Pre (< 45): 62 (51.2%) Post (> 55): 59 (48.8%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Prospecitive women with mass who had surgery in time frame Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) DePriest ≥ 5 

 Dis+ Dis- Tot T+ 13 28 41 

T- 0 80 80 Tot 13 108 121  Lower Upper  Value 95% CI 95% CI Se 100.0% 76.9% 100.0%Sp 74.1% 65.8% 82.3% PPV 31.7% 17.5% 46.0% NPV 100.0% 96.3% 100.0%

Comme--Only n reporteanalysis --No disobserve--No discalculat--ClinicaQuality ReferenVerificaTest reSample StatisticBlindingDefinitio
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

and negative on screening test: Morphology index score ≥ 5 (Table 1) 

DePriest, van Nagell Jr., Gallion, et al., 1993 #6880 

Geographical location: Kentucky USA University Dates: Nov 1987 - June 

1992 Size of population: 44/3220 Screening study Reference standard: For women with abnormal TVUS - pathology Reference standard applied to all test negatives?: No Test reliability established?: No Statistical tests used: Fischer’s exact test Blinding: NR - prospective Definition of positive and negative on screening test: US – ovarian volume > 10 cm3 or “cystic ovarian 

tumor with a papillary projection into its lumen” Also DePriest score also 

Age: Mean: 60 Range: 33-90 Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): Family history: 502 (15.6%) ovarian CA 1034 (32.1%) breast CA 678 (21.1%) colon CA Inclusion criteria: Volunteers for screening program at U of K Exclusion criteria: Individuals with prior history of ovarian cancer or pelvic radiation 

Symptomatic (n [%]): 0 (0%) Detected by exam (n [%]): NA Detected by imaging (n [%]): NA Combination (n [%]): NR Additional data used for diagnosis: NR 

1) US score ≥ 5 

 Dis+ Dis- Tot T+ 3 6 9 

T- 0 15 15 Tot 3 21 24  Lower Upper  Value 95% CI 95% CI Se 100.0% 0.0% 100.0%Sp 71.4% 52.1% 90.8% PPV 33.3% 2.5% 64.1% NPV 100.0% 80.0% 100.0%

Comme--Scree--Test nyear (dofollow u--No disDePriesQuality ReferenVerificaTest reSample StatisticBlindingDefinitio
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

used (but unclear how used at what cutoff) 

DePriest, Varner, Powell, et al., 1994 #10950 

Geographical location: USA Dates: NR 

Size of population: 213 Retrospective chart review with re-analysis of US data Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: Kappa statistic, Regression analysis Blinding: Yes Definition of positive and negative on screening test: DePriest morphology index score >=5 

Age: For benign tumors mean 44.9 with range (16-84) For malignant mean 53.8 (25-78) Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: NR Exclusion criteria: 11 patients excluded due to lack of US or surgical information 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) RI ≥ 0.5 

 Dis+ Dis- Tot T+ 39 46 85 

T- 5 123 128 Tot 44 169 213  Lower Upper  Value 95% CI 95% CI Se 89.0% 79.8% 98.2% Sp 73.0% 66.3% 79.7% 

PPV 45.9% 35.3% 56.5% NPV 96.1% 92.7% 99.5% 

Comme--LMP g--Good --TVUS Quality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-80

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommDowd, Quinn, Rome, et al., 1993 #4680 

Geographical location: Melbourne, AU Dates: 1978 to 1989 

Size of population: 264 patients total although not all had ultrasound, CA-125 and exam results Other Retrospective chart review Reference standard: Pathology Reference standard applied to all test negatives?: Yes Test reliability established?: NR Statistical tests used: Chi square or Fishers Blinding: Tried to predict disease outcome based on clinical exam and ultrasound Definition of positive and negative on screening test: CA ≤ 35 u/ml considered 

normal US impression of reviewer drawn from US report (not film review): “simple, smooth, and/or 

Age: Range: 15-35 for premenopausal Range: 40 –89 for post Menopausal status (n [%]): Pre (< 45): 121 Post (> 55): 143 Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Patients who had CA-125 performed in presence of pelvic mass Exclusion criteria: 

Test performed for screening purposes only, in absence of pelvic mass excluded Inadequate documentation for pathology. 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) CA-125 premenopausal 

 Dis+ Dis- Tot T+ 32 21 53 

T- 11 57 68 Tot 43 78 121  Lower Upper  Value 95% CI 95% CI Se 74.0% 60.9% 87.1% Sp 73.0% 63.1% 82.9% 

PPV 60.4% 47.2% 73.5% NPV 83.8% 75.1% 92.6% 

2) CA-125 post menopausal 

 Dis+ Dis- Tot T+ 80 9 89 

T- 13 41 54 Tot 93 50 143  Lower Upper  Value 95% CI 95% CI Se 86.0% 78.9% 93.1% Sp 82.0% 71.4% 92.6% 

PPV 89.9% 83.6% 96.2% NPV 75.9% 64.5% 87.3% 

3) CA-125 all patients 

 Dis+ Dis- Tot T+ 112 30 142 

T- 24 98 122 Tot 136 128 264  Lower Upper  Value 95% CI 95% CI Se 82.4% 75.9% 88.8% Sp 76.6% 69.2% 83.9% PPV 78.9% 72.2% 85.6% NPV 80.3% 73.3% 87.4% 

4) Ultrasound all patients 

Comme--Unablstratifiefor premSensitivpostmespecific--LMP tmaligna--ClinicaQuality ReferenVerificaTest reSample StatisticBlindingDefinitio
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

unilateral likely to be benign; “solid or mixed consistency, bilateral, irregular or associated ascites...likely malignancy” Clinical exam: “mass hard, irregular, fixed, attached to other structures.” 

 Dis+ Dis- Tot T+ 61 17 78 

T- 14 90 104 Tot 75 108 183  Lower Upper  Value 95% CI 95% CI Se 81.0% 72.1% 89.9% Sp 84.0% 77.1% 90.9% 

PPV 78.0% 68.8% 87.2% 

NPV 86.0% 79.3% 92.7% 

Einhorn, Bast Jr., Knapp, et al., 1986 #6860 

Geographical location: Sweden Dates: Since 1983 – 

dates unclear Size of population: 100 Other Retrospective comparison of serum samples with operative outcomes Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: Se, Sp Blinding: NR 

Age: NR Menopausal status (n [%]): NR Race/ethnicity (n [%]): Swedish Risk factors (n [%]): NR Inclusion criteria: Patients with pelvic mass who had surgery For whom banked serum present Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) CA-125 > 35 (excluding non-ovarian primary) 

 Dis+ Dis- Tot T+ 14 9 23 

T- 4 73 77 Tot 18 82 100  Lower Upper  Value 95% CI 95% CI Se 77.8% 58.6% 97.0% Sp 89.0% 82.3% 95.8% PPV 60.9% 40.9% 80.8% NPV 94.8% 89.8% 99.8% 

2) CA-125 > 35 (includes metastatic disease) 

 Dis+ Dis- Tot T+ 18 5 23 T- 5 72 77 Tot 23 77 100  Lower Upper  Value 95% CI 95% CI Se 78.3% 61.4% 95.1% Sp 93.5% 88.0% 99.0% PPV 78.3% 61.4% 95.1% NPV 93.5% 88.0% 99.0% 

2) CA-125 > 35 (classifying borderline as “benign” 

Comme--Bordemaligna--Slight specificfrom tex--No staQuality ReferenVerificaTest reSample StatisticBlindingDefinitio
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

Definition of positive and negative on screening test: CA-125 > 35 U/ml 

 Dis+ Dis- Tot T+ 16 7 23 

T- 5 72 77 Tot 21 79 100  Lower Upper  Value 95% CI 95% CI Se 76.2% 58.0% 94.4% Sp 91.1% 84.9% 97.4% PPV 69.6% 50.8% 88.4% NPV 93.5% 88.0% 99.0% 

Ekerhovd, Wienerroith, Staudach, et al, 2001 #8780 

Geographical location: Salzburg, Austria, and Goteborg, Sweden Dates: Jan 1992-Dec 

1997 Size of population: 1304 Other Case series of all women with unilocular adnexal cyst on transvaginal US Reference standard: Surgery Reference standard applied to all test negatives?: Yes Test reliability established?: No Statistical tests used: t-test, chi-square Blinding: 

Age: Range: 14-90 NR for entire group Menopausal status (n [%]): Pre (< 45): 927 (71.1%) Post (> 55):377 (28.9%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Scheduled for surgery and unilocular cyst Exclusion criteria: Presence of internal septae 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Low malignant potential = benign, presence of solid areas or papillations = positive test 

 Dis+ Dis- Tot T+ 13 631 644 

T- 4 656 660 Tot 17 1287 1304  Lower Upper  Value 95% CI 95% CI Se 76.5% 56.3% 96.6% Sp 51.0% 48.2% 53.7% PPV 2.0% 0.9% 3.1% NPV 99.4% 98.8% 100.0%

2) Low malignant potential = cancer 

 Dis+ Dis- Tot T+ 24 620 644 T- 7 653 660 Tot 31 1273 1304  Lower Upper  Value 95% CI 95% CI Se 77.4% 62.7% 92.1% Sp 51.3% 48.6% 54.0% PPV 3.7% 2.3% 5.2% NPV 98.9% 98.2% 99.7% 

Comme--TVUS Quality ReferenVerificaTest reSample StatisticBlindingDefinitio
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

Definition of positive and negative on screening test: Suspicious: unilocular with small solid areas or papillary formation Benign: Simple cysts 

Fenchel, Grab, Nuessle, et al., 2002 #2220 

Geographical location: Ulm, Germany University hospital Dates: May 1997 – Feb 

1999 Size of population: 99 women Other Consecutive patients referred to hospital Reference standard: Histopathology Reference standard applied to all test negatives?: 97 had histopathology, 1 had cytology 1 US follow up Test reliability established?: No for PET Yes for US ? for MRI Statistical tests used: Se, Sp, PPV, NPV Blinding: 

Yes

Age: Mean (SD):46(15) Range: 18-83 Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Consecutive, asymptomatic “sonographically suspect” (by referring physician adnexal mass referred to hospital Exclusion criteria: Pregnant women, clinical symptoms of malignancy, under 18 years 

Symptomatic (n [%]): 0 (0%) Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Combined US and Doppler 

 Dis+ Dis- Tot T+ 11 35 46 

T- 1 52 53 Tot 12 87 99  Lower Upper  Value 95% CI 95% CI Se 92.0% 76.7% 100.0%Sp 60.0% 49.7% 70.3% 

PPV 23.9% 11.6% 36.2% NPV 98.1% 94.5% 100.0%

2) MRI 

 Dis+ Dis- Tot T+ 10 15 25 

T- 2 72 74 Tot 12 87 99  Lower Upper  Value 95% CI 95% CI Se 83.0% 61.7% 100.0%Sp 83.0% 75.1% 90.9% 

PPV 40.0% 20.8% 59.2% NPV 97.3% 93.6% 100.0%

3) FDG PET 

 Dis+ Dis- Tot T+ 7 21 28 

T- 5 66 71 Tot 12 87 99 

Comme--Three (DePrieeach is contribufor this in serie--Hospibased --Bordeprobabcategorof bordedescrip--May bas GraQuality Referentime for case noVerificaTest recomponunclear togethediagnosOther teSample StatisticBlindingDefinitio+/- 
D-84

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

Definition of positive and negative on screening test: For PET – “interpreted visually in consensus” by “2 or 3 experiences nuclear med physicians For FDG uptake – “subjective” scale US DePriest,(≥ 5), Kawai (9-12 = malignant) and Doppler RI < 0.45 = malignant 

 Lower Upper  Value 95% CI 95% CI Se 58.0% 30.1% 85.9% 

Sp 76.0% 67.0% 85.0% 

PPV 25.0% 9.0% 41.0% NPV 93.0% 87.0% 98.9% 

Ferdeghini, Gadducci, Prontera, et al., 1993 #4710 

Geographical location: Italy Dates: NR 

Size of population: 183 Other 2 retrospective samples: one if cancer one if benign – both consecutive Reference standard: Histology Reference standard applied to all test negatives?: Yes Test reliability established?: No Statistical tests used: Student t test Chi square Fishers exact test 

Age: Median (with range): Ovarian cancer = 60 (35-91) Benign = 35 (13 – 76) Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Had pre-operative levels of SIL-2R and CA-125 Exclusion criteria: Autoimmune or rheumatic disease 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) CA-125 

 Dis+ Dis- Tot T+ 42 9 51 

T- 12 120 132 Tot 54 129 183  Lower Upper  Value 95% CI 95% CI Se 77.8% 66.7% 88.9% Sp 93.0% 88.6% 97.4% 

PPV 82.4% 71.9% 92.8% NPV 90.9% 86.0% 95.8% 

Comme--CA-12Quality ReferenVerificaTest reSample StatisticBlindingDefinitio
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

Blinding: NR Definition of positive and negative on screening test: CA-125 ≥ 83 U/ml. 

Ferrazzi, Zanetta, Dordoni, et al., 1997 #3570 

Geographical location: Milan, Italy University Dates: 1995-96 (2 yrs) 

Size of population: 330 masses Other Case series in multicenter Reference standard: Pathology Reference standard applied to all test negatives?: Yes Test reliability established?: Sassone – yes DePriest – yes This study – no Statistical tests used: ROC curve Blinding: NR - prospective Definition of positive and negative on screening test: Sassone (per original 

Age: Mean (SD): 45 (16) Range: 19-89 Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Surgery within 7 days of US, detailed pathology available, women with mass in time frame at three hospitals in Italy Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) This study > 9 

 Dis+ Dis- Tot T+ 60 86 146 

T- 9 175 184 Tot 69 261 330  Lower Upper  Value 95% CI 95% CI Se 87.0% 79.1% 94.9% Sp 67.0% 61.3% 72.7% 

PPV 41.1% 33.1% 49.1% NPV 95.1% 92.0% 98.2% 

2) Sassone > 9 

 Dis+ Dis- Tot T+ 51 91 142 

T- 18 170 188 Tot 69 261 330  Lower Upper  Value 95% CI 95% CI Se 74.0% 63.7% 84.3% Sp 65.0% 59.2% 70.8% 

PPV 35.9% 28.0% 43.8% NPV 90.4% 86.2% 94.6% 

3) DePriest 

 Dis+ Dis- Tot T+ 61 157 218 

T- 8 104 112 Tot 69 261 330  Lower Upper 

Comme--No disobservenew sco--No po--Good testing Quality ReferenVerificaTest reSample StatisticBlindingDefinitio+/- 
D-86

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

article) > 9 DePriest (per original article) > 5 This study – Table 2 > 9 

 Value 95% CI 95% CI Se 88.0% 80.3% 95.7% 

Sp 40.0% 34.1% 45.9% 

PPV 28.0% 22.0% 33.9% NPV 92.9% 88.1% 97.6% 
D-87

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommFinkler, Benacerraf, Lavin, et al., 1988 #1230 

Geographical location: Boston, MA Dates: Nov 1986 to Apr 

1987 Size of population: 131 consecutive patients 106 eventually retained Other Prospective series Reference standard: Pathology Reference standard applied to all test negatives?: 

Yes

Test reliability established?: NR Statistical tests used: Fisher’s exact Blinding: Yes Definition of positive and negative on screening test: CA-125 > 35 U/mL considered positive US had two evaluations first (Table 1) Finkler score ≥ 7 = malignant second Primary US = impression only 

Age: Mean: 45.2 Range: 17-84 Menopausal status (n [%]): 74Pre (< 45): Peri (45-55): Post (> 55): Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Ovarian mass who were scheduled to under exploratory laparotomy Had a pre-operative ultrasound Consecutive patients Exclusion criteria: Original ultrasound unavailable or uninterpretable. Pregnant or with histologic cancer diagnosis 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Original ultrasound – premenopausal 

 Dis+ Dis- Tot T+ 2 2 4 

T- 16 54 70 Tot 18 56 74  Lower Upper  Value 95% CI 95% CI Se 11.0% 0.0% 25.5% Sp 96.0% 90.9% 100.0%

PPV 50.0% 1.0% 99.0% NPV 77.1% 67.3% 87.0% 

2) Specialist ultrasound – premenopausal 

T+ 9 2 11 T- 9 54 63 

Tot 18 56 74  Lower Upper  Value 95% CI 95% CI Se 50.0% 26.9% 73.1% Sp 96.0% 90.9% 100.0%

PPV 81.8% 59.0% 100.0%NPV 85.7% 77.1% 94.4% 

3) CA-125 – premenopausal 

 Dis+ Dis- Tot T+ 9 17 26 

T- 9 39 48 Tot 18 56 74  Lower Upper  Value 95% CI 95% CI Se 50.0% 26.9% 73.1% Sp 69.0% 56.9% 81.1% 

PPV 34.6% 16.3% 52.9% NPV 81.3% 70.2% 92.3% 

4) Original US – postmenopausal 

Comme--Origincancer --“Specsystem --Uncleblinded --Abdom--CA-12positive values when aprior ultQuality ReferenVerificaTest reSample StatisticBlindingDefinitio + 
D-88

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

 Dis+ Dis- Tot T+ 9 2 11 

T- 10 11 21 Tot 19 13 32  Lower Upper  Value 95% CI 95% CI Se 47.0% 24.6% 69.4% Sp 85.0% 65.6% 100.0%

PPV 81.8% 59.0% 100.0%NPV 52.4% 31.0% 73.7% 

5) Specialist US – postmenopausal 

 Dis+ Dis- Tot T+ 15 1 16 

T- 4 12 16 Tot 19 13 32  Lower Upper  Value 95% CI 95% CI Se 78.0% 59.4% 96.6% Sp 92.0% 77.3% 100.0%

PPV 93.8% 81.9% 100.0%NPV 75.0% 53.8% 96.2% 

6) CA-125 – postmenopausal 

 Dis+ Dis- Tot T+ 16 1 17 

T- 3 12 15 Tot 19 13 32  Lower Upper  Value 95% CI 95% CI Se 84.0% 67.5% 100.0%Sp 92.0% 77.3% 100.0%

PPV 94.1% 82.9% 100.0%NPV 80.0% 59.8% 100.0%

7) CA-125 – all ages combined 

 Dis+ Dis- Tot T+ 25 18 43 

T- 12 51 63
D-89

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

Tot 37 69 106 

 Lower Upper  Value 95% CI 95% CI Se 67.6% 52.5% 82.7% Sp 73.9% 63.6% 84.3% PPV 58.1% 43.4% 72.9% NPV 81.0% 71.3% 90.6% 

8) US total 

 Dis+ Dis- Tot T+ 24 55 79 T- 22 68 90 Tot 46 123 169  Lower Upper  Value 95% CI 95% CI Se 52.2% 37.7% 66.6% Sp 55.3% 46.5% 64.1% PPV 30.4% 20.2% 40.5% NPV 75.6% 66.7% 84.4% 
D-90

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommFleischer, Rodgers, Kepple, et al., 1992 #6460 

Geographical location: Nashville, TN Dates: NR 

Size of population: 62 Other Case series Reference standard: Pathology Reference standard applied to all test negatives?: Yes Test reliability established?: No Statistical tests used: Se, Sp Blinding: NR Definition of positive and negative on screening test: PI < 1.0 

Age: NR Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: NR – mass – surgery - USExclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Doppler 

 Dis+ Dis- Tot T+ 17 1 18 

T- 3 41 44 Tot 20 42 62  Lower Upper  Value 95% CI 95% CI Se 85.0% 69.4% 100.0%Sp 97.6% 93.0% 100.0%PPV 94.4% 83.9% 100.0%NPV 93.2% 85.7% 100.0%

Comme--2x2 tatext or f--Table positiveand senQuality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-91

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommFranchi, Beretta, Ghezzi, et al., 1995 #6270 

Geographical location: Italy Dates: Jan 1991 to Dec 

1993 Size of population: 129 Screening study Case series Reference standard: Pathology Reference standard applied to all test negatives?: Yes Test reliability established?: NR Statistical tests used: Mann-Witney U ROC curves Blinding: US blinded to lab results Definition of positive and negative on screening test: 2D Ultrasound: Maximum diameter (5 cm), solid areas, high echogenicity, multilocular appearance, irregular borders, papillary intracystic vegetations, presence of ascites Color Doppler Imaging RI = systolic peak –

Age: Median: 44 Range: 12-91 Menopausal status (n [%]): Pre (< 45): 83 (64.3%) Peri (45-55): NR Post (> 55): NR Race/ethnicity (n [%]): Italian Risk factors (n [%]): NR Inclusion criteria: Abnormal findings on pelvic exam and 2D sonographic features of adnexal mass Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Premenopausal - CA-125 

 Dis+ Dis- Tot T+ 8 26 34 

T- 3 46 49 Tot 11 72 83  Lower Upper  Value 95% CI 95% CI Se 72.7% 46.4% 99.0% Sp 63.8% 52.7% 74.9% 

PPV 23.5% 9.3% 37.8% NPV 93.9% 87.2% 100.0%

2) Premenopausal - Sonography 

 Dis+ Dis- Tot T+ 8 10 18 

T- 3 62 65 Tot 11 72 83  Lower Upper  Value 95% CI 95% CI Se 72.7% 46.4% 99.0% Sp 86.1% 78.1% 94.1% 

PPV 44.4% 21.5% 67.4% NPV 95.4% 90.3% 100.0%

3) Combined ages 

 Dis+ Dis- Tot T+ 31 15 46 

T- 6 77 83 Tot 37 92 129  Lower Upper  Value 95% CI 95% CI Se 83.8% 71.9% 95.7% Sp 83.7% 76.1% 91.2% PPV 67.4% 53.8% 80.9% NPV 92.8% 87.2% 98.3% 

4) Premenopausal - Color Doppler Imaging 

Comme--ROC cutoff --CA-12--No US descripQuality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-92

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

diastolic peak/systolic peak. Artery with lowest RI considered to indicate the malignant potential of the tumor. RI < 0.65 CA-125 ≥ 40UI/ml 

suspected of malignant pelvic tumor 

 Dis+ Dis- Tot T+ 9 20 29 

T- 2 52 54 Tot 11 72 83  Lower Upper  Value 95% CI 95% CI Se 81.8% 59.0% 100.0%Sp 72.2% 61.9% 82.5% 

PPV 31.0% 14.2% 47.9% NPV 96.3% 91.3% 100.0%

5) Color Doppler Imaging - combined ages 

 Dis+ Dis- Tot T+ 30 26 56 

T- 7 66 73 Tot 37 92 129  Lower Upper  Value 95% CI 95% CI Se 81.1% 68.5% 93.7% Sp 71.7% 62.5% 80.9% PPV 53.6% 40.5% 66.6% NPV 90.4% 83.7% 97.2% 

6) Postmenopausal – CA-125 

 Dis+ Dis- Tot T+ 20 3 23 T- 6 17 23 Tot 26 20 46  Lower Upper  Value 95% CI 95% CI Se 76.9% 60.7% 93.1% Sp 85.0% 69.4% 100.0%

PPV 87.0% 73.2% 100.0%NPV 73.9% 56.0% 91.9% 

7) All ages CA-125 

 Dis+ Dis- Tot T+ 28 29 57 

T- 9 63 72
D-93

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

Tot 37 92 129 

 Lower Upper  Value 95% CI 95% CI Se 75.7% 61.9% 89.5% Sp 68.5% 59.0% 78.0% PPV 49.1% 36.1% 62.1% NPV 87.5% 79.9% 95.1% 

8) Postmenopausal - Sonography 

 Dis+ Dis- Tot T+ 23 5 28 T- 3 15 18 Tot 26 20 46  Lower Upper  Value 95% CI 95% CI Se 88.5% 76.2% 100.0%Sp 75.0% 56.0% 94.0% 

PPV 82.1% 68.0% 96.3% NPV 83.3% 66.1% 100.0%

9) Postmenopausal - Color Doppler Imaging

 Dis+ Dis- Tot T+ 21 6 27 

T- 5 14 19 Tot 26 20 46  Lower Upper  Value 95% CI 95% CI Se 81.8% 67.0% 96.6% Sp 72.2% 52.6% 91.8% 

PPV 77.8% 62.1% 93.5% NPV 73.7% 53.9% 93.5% 
D-94

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommGadducci, Baicchi, Marrai, et al., 1996 #6230 

Geographical location: Pisa, Italy University Hospital Dates: NR 

Size of population: 124 women (3 excluded = 121) Other Consecutive patients referred for surgery with diagnosis of ovarian mass Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: Mann-Whitney U test Spearman rank correlation test Logistic regression ROC curves Blinding: No – but consecutive enrollment Definition of positive and negative on screening test: CA-125 > 65 U/ml D-Dimer > 416 ng/ml 

Age: NR Menopausal status (n [%]): Pre: 57 (47.1%) Post: 64 (52.9%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Consecutive women with clinical diagnosis of ovarian mass to undergo surgery Exclusion criteria: Cardiovascular disease, diabetes, acute or chronic inflammatory disease, previous malignancy, or previous episodes of thrombophlebitis or thromboembolia. 2 patients excluded for uterine fibroid (after surgery) 1 excluded for leiomyosarcoma, of small bowel 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) CA-125 > 65 U/ml – premenopause 

 Dis+ Dis- Tot T+ 8 4 12 

T- 4 41 45 Tot 12 45 57  Lower Upper  Value 95% CI 95% CI Se 66.7% 40.0% 93.4% Sp 91.1% 82.8% 99.4% 

PPV 66.7% 40.0% 93.3% NPV 91.1% 82.8% 99.4% 

2) D-Dimer - premenopause 

 Dis+ Dis- Tot T+ 12 4 16 

T- 0 41 41 Tot 12 45 57  Lower Upper  Value 95% CI 95% CI Se 100.0% 75.0% 100.0%Sp 91.1% 82.8% 99.4% 

PPV 75.0% 53.8% 96.2% NPV 100.0% 92.7% 100.0%

3) D-Dimer – combined ages 

 Dis+ Dis- Tot T+ 51 11 62 

T- 5 54 59 Tot 56 65 121  Lower Upper  Value 95% CI 95% CI Se 91.1% 83.6% 98.5% Sp 83.1% 74.0% 92.2% PPV 82.3% 72.7% 91.8% NPV 91.5% 84.4% 98.6% 

4) CA-125 > 65 U/ml - postmenopause 

Comme--Most study wet al., 1--Age bmenopahoweveby men--Cutoff --D-Dimpreviou(using msame a--D-dimlikely ovare not to selecQuality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-95

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

 Dis+ Dis- Tot T+ 35 0 35 T- 9 20 29 Tot 44 20 64  Lower Upper  Value 95% CI 95% CI Se 79.5% 67.6% 91.4% Sp 100.0% 85.0% 100.0%

PPV 100.0% 91.4% 100.0%NPV 69.0% 52.1% 85.8% 

5) CA-125 > 65 U/ml – all ages 

 Dis+ Dis- Tot T+ 43 4 47 

T- 13 61 74 Tot 56 65 121  Lower Upper  Value 95% CI 95% CI Se 76.8% 65.7% 87.8% Sp 93.8% 88.0% 99.7% PPV 91.5% 83.5% 99.5% NPV 82.4% 73.8% 91.1% 

6) D-Dimer - postmenopause 

 Dis+ Dis- Tot T+ 39 7 46 T- 5 13 18 Tot 44 20 64  Lower Upper  Value 95% CI 95% CI Se 88.6% 79.2% 98.0% Sp 65.0% 44.1% 85.9% 

PPV 84.8% 74.4% 95.2% NPV 72.2% 51.5% 92.9% 
D-96

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommGadducci, Capriello, Bartolini, et al., 1988 #6650 

Geographical location: Pisa Italy University Hospital Dates: NR 

Size of population: 119 women OtherPatients undergoing surgery for mass Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: For CA-125 – yes For US – no Statistical tests used: Sensitivity, specificity Blinding: 

No – probably prospectiveDefinition of positive and negative on screening test: US scoring system ≥ 10 (of 16 with 4 points for shape, ascites, outline, and structure) 

Age: NR Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Patients undergoing surgery for mass Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) CA-125 ≥ 35 U/ml 

 Dis+ Dis- Tot T+ 31 20 51 

T- 5 63 68 Tot 36 83 119  Lower Upper  Value 95% CI 95% CI Se 86.1% 74.8% 97.4% Sp 75.9% 66.7% 85.1% 

PPV 60.8% 47.4% 74.2% NPV 92.6% 86.4% 98.9% 

2) US 

 Dis+ Dis- Tot T+ 26 2 28 

T- 10 81 91 Tot 36 83 119  Lower Upper  Value 95% CI 95% CI Se 72.2% 57.6% 86.8% Sp 97.9% 94.8% 100.0%

PPV 92.9% 83.3% 100.0%NPV 89.0% 82.6% 95.4% 

Comme--US scnot grounique specificunclear --CA-12by authonly for in comm--PatienGaddu--ReferQuality ReferenVerificaTest regiven thSample StatisticBlindingDefinitio
D-97

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommGadducci, Ferdeghini, Prontera, et al., 1992 #6850 

Geographical location: Italy Dates: NR 

Size of population: 344 Other Consecutive case series Reference standard: Pathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes for CA-125 Statistical tests used: Chi-square Blinding: NR Definition of positive and negative on screening test: CA-125 35 and 65 U/ml 

Age: NR Menopausal status (n [%]): NRRace/ethnicity (n [%]): Italian Risk factors (n [%]): NR Inclusion criteria: Patients undergoing laparotomy for ovarian masses Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) CA-125 ≥ 65 U/ml (Age < 50 years) 

 Dis+ Dis- Tot T+ 8 146 154 

T- 8 51 59 Tot 16 197 213  Lower Upper  Value 95% CI 95% CI Se 50.0% 25.5% 74.5% Sp 26.0% 19.9% 32.1% 

PPV 5.2% 1.7% 8.7% NPV 86.4% 77.7% 95.2% 

2) CA-125 ≥ 65U/ml (Age ≥ 50) 

 Dis+ Dis- Tot T+ 60 8 68 

T- 14 49 63 Tot 74 57 131  Lower Upper  Value 95% CI 95% CI Se 81.1% 72.2% 90.0% Sp 86.0% 77.0% 95.0% 

PPV 88.2% 80.6% 95.9% NPV 77.8% 67.5% 88.0% 

3) CA-125 ≥ 35 (for all ages) 

 Dis+ Dis- Tot T+ 74 83 157 

T- 16 171 187 Tot 90 254 344  Lower Upper  Value 95% CI 95% CI Se 82.3% 74.4% 90.2% Sp 67.3% 61.5% 73.1% 

PPV 47.1% 39.3% 54.9% NPV 91.4% 87.4% 95.5% 

4) CA-125 ≥ 65 (for all ages) 

Comme--Data sstatus fcutpoin--Appeagrouped --UncledefinitioQuality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-98

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

 Dis+ Dis- Tot T+ 68 154 222 T- 22 100 122 Tot 90 254 344  Lower Upper  Value 95% CI 95% CI Se 75.6% 66.7% 84.4% Sp 39.4% 33.4% 45.4% PPV 30.6% 24.6% 36.7% NPV 82.0% 75.1% 88.8% 

Gadducci, Ferdeghini, Rispoli, et al., 1991 #6490 

Geographical location: Pisa, Italy University Hospital Dates: NR 

Size of population: 220 women Other Preop patients at university hospital Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: Se, Sp Blinding: NR but serum drawn prior to surgery 

Age: NR Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: NR aside from undergoing gynecological surgery (presumably for mass) Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: None 

1) CA-125 > 35 U/ml 

Dis+ Dis- Tot 

T+ 49 66 115 

T- 8 97 105 Tot 57 163 220  Lower Upper  Value 95% CI 95% CI Se 86.0% 77.0% 95.0% Sp 59.5% 52.0% 67.0% 

PPV 42.6% 33.6% 51.6% NPV 92.4% 87.3% 97.5% 

Comme--No de--Hospi--Althouthis was becausQuality ReferenVerificaTest reSample StatisticBlindingprospecDefinitio
D-99

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

Definition of positive and negative on screening test: CA-125 > 35 (or 65) U/ml 

Grab, Flock, Stohr, et al., 2000 #2720 

Geographical location: Germany Dates: NR 

Size of population: 101 OtherCase series Reference standard: Yes Reference standard applied to all test negatives?: Yes Test reliability established?: NR Statistical tests used: None Blinding: Yes Definition of positive and negative on screening test: Sonography: Adnexal masses with suspicious patterns according to Sawai’s classification, DePriest score ≥ 5 or RI < 0.45 assumed to be malignant 

Age: Median: 45 Range: 18-82 Menopausal status (n [%]): NRRace/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Asymptomatic adnexal mass Prospective consecutive patients scheduled for laproscopy offered entry Exclusion criteria: Pregnant women, age < 18 and patients with clinical symptoms of malignancy 

Symptomatic (n [%]): NR – but assume 0% since excluded Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Ultrasound – combination morphology and Doppler 

 Dis+ Dis- Tot T+ 11 36 47 

T- 1 53 54 Tot 12 89 101  Lower Upper  Value 95% CI 95% CI Se 92.0% 76.7% 100.0%Sp 60.0% 49.8% 70.2% 

PPV 23.4% 11.3% 35.5% NPV 98.1% 94.6% 100.0%

2) MRI 

 Dis+ Dis- Tot T+ 10 14 24 

T- 2 75 77 Tot 12 89 101  Lower Upper  Value 95% CI 95% CI Se 83.0% 61.7% 100.0%Sp 84.0% 76.4% 91.6% 

PPV 41.7% 21.9% 61.4% NPV 97.4% 93.8% 100.0%

3) PET 

 Dis+ Dis- Tot T+ 7 18 25 

T- 5 71 76 Tot 12 89 101  Lower Upper 

Value 95% CI 95% CI

Comme--No desurgery --Unclediagnos--DescrCT; no --RI cut why cho--No disobserve--Uncleand Doparallel --One ostate prsymptoQuality ReferenVerificaTest reSample StatisticBlindingDefinitio +, but describ
D-100

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

MRI Lesions considered benign if one or more of the following were met: cystic structures without any solid areas, diameter 4 cm or less wall thickness < 3 mm and presence of typical characteristics of dermoid cyst or endometrioma. If one of these not fulfilled then considered malignant. PET If uptake of F-FDG equaled or exceeded that of the liver and they were not localized within structures with physiologic uptake. COMBINATION All 3 used in conference, but criteria not described 

Se 58.0% 30.1% 85.9% 

Sp 80.0% 71.7% 88.3% 

PPV 28.0% 10.4% 45.6% NPV 93.4% 87.8% 99.0% 

4) All 3 (definition of positive/negative not given) 

 Dis+ Dis- Tot T+ 11 13 24 

T- 1 76 77 Tot 12 89 101  Lower Upper  Value 95% CI 95% CI Se 92.0% 76.7% 100.0%Sp 85.0% 77.6% 92.4% 

PPV 45.8% 25.9% 65.8% NPV 98.7% 96.2% 100.0%
D-101

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommGranberg, Norstrom, and Wikland, 1990 #5320 

Geographical location: Sweden Dates: 1987-1988 

Size of population: 180 OtherProspective series Reference standard: Pathology Reference standard applied to all test negatives?: Yes Test reliability established?: Used the same MD for all exams Statistical tests used: None Blinding: NR Definition of positive and negative on screening test: “Classified as malignant the more complex it looked on ultrasound” 

Age: Range: < 20 to > 70 Menopausal status (n [%]): Pre (< 45): 86 (48%) Post (> 55): 94 (52%) Race/ethnicity (n [%]): Swedish Risk factors (n [%]): NR Inclusion criteria: Women scheduled for elective surgery due to adnexal masses Exclusion criteria: NR 

Symptomatic (n [%]): 71% had symptoms Detected by exam (n [%]): 100% found at a gyn exam performed 1 week to 1 month prior to surgery, but unclear whether symptoms present Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Vaginal ultrasound (data not presented by menopausal status) 

 Dis+ Dis- Tot T+ 32 11 43 

T- 7 130 137 Tot 39 141 180  Lower Upper  Value 95% CI 95% CI Se 82.1% 70.0% 94.1% Sp 92.2% 87.8% 96.6% PPV 74.4% 61.4% 87.5% NPV 94.9% 91.2% 98.6% 

Comme--No US descrip--UncleconsecQuality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-102

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommGranberg, Norstrom, and Wikland, 1991 #10920 

Geographical location: Sweden Dates: May 1988 – Dec 

1988 Size of population: 50 Case series Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Not really Statistical tests used: Student’s T test Linear regression Se, Sp Blinding: NR Definition of positive and negative on screening test: US – at least one of the following criteria fulfilled: 1) tumor > 10 cm in diameter (excluding simple completely unilocular cysts), 2) unilocular with echogenic areas inside the cyst, 3) multilocular with more than one thick (> 1 mm) septation and internal 

Age: Mean: 53.8 Range: 21-92 Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Surgical series Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) US – all patients 

 Dis+ Dis- Tot T+ 16 6 22 

T- 0 28 28 Tot 16 34 50  Lower Upper  Value 95% CI 95% CI Se 100.0% 81.3% 100.0%Sp 82.0% 69.1% 94.9% 

PPV 72.7% 54.1% 91.3% NPV 100.0% 89.3% 100.0%

Comme--No scmorphoreprodu--Clinicapatients --TVUS Quality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-103

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

echoes, 4) multilocularsolid. 

Guerriero, Ajossa, Garau, et al., 2005 #7470 

Geographical location: Cagliari, Italy Dates: NR 

Size of population: 424 women 453 masses Case series

Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Not really Statistical tests used: Se, Sp Kappa statistic, Blinding: NR Definition of positive and negative on screening test: US morphology : benign was anything that resembled an endometrioma, or a cystic teratoma, or with appearance of nonmalignant(not defined) Doppler – not clearly stated but appears to be 

Age: Mean (SD): 39 (15) Range: 14-79 Menopausal status (n [%]): Pre (< 45): 323 (76%) Post (> 55): 101 (24%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: NR Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) US morphology 

 Dis+ Dis- Tot T+ 95 64 159 

T- 0 294 294 Tot 95 358 453  Lower Upper  Value 95% CI 95% CI Se 100.0% 96.8% 100.0%Sp 82.0% 78.0% 86.0% 

PPV 59.7% 52.1% 67.4% NPV 100.0% 99.0% 100.0%

2) Doppler 

 Dis+ Dis- Tot T+ 95 32 127 

T- 0 326 326 Tot 95 358 453  Lower Upper  Value 95% CI 95% CI Se 100.0% 96.8% 100.0%Sp 91.0% 88.0% 94.0% 

PPV 74.8% 67.3% 82.4% NPV 100.0% 99.1% 100.0%

Comme--Definiscan or some sscore o--Kappa --TVUS Quality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-104

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

simple presence or absence of flow visualized in “echogenic structure” 

Guerriero, Ajossa, Risalvato, et al., 1998 #3400 

Geographical location: Italy Dates: Jan 1996-May 

1997 Size of population: 240 178 women with 192 masses Other Prospective series Reference standard: Pathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: Kappa for reliability Blinding: NR Definition of positive and negative on screening test: B-mode: Malignant when echogenic structure situated adjacent to wall of cyst is present, when a large > 3 mm irregular 

Age: Mean (SD): 41 (15) Range: 14-77 Menopausal status (n [%]): Pre (< 45): 127 (71%) Post (> 55): 51 (29%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Women under observation for presence of adnexal mass Exclusion criteria: Pregnant 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

Estimates are for masses not women 1) Post menopause PI ≤ 1 

 Dis+ Dis- Tot T+ 23 12 35 

T- 3 13 16 Tot 26 25 51  Lower Upper  Value 95% CI 95% CI Se 88.0% 75.5% 100.0%Sp 52.0% 32.4% 71.6% 

PPV 65.7% 50.0% 81.4% NPV 81.3% 62.1% 100.0%

2) Total for PI ≤ 1 

 Dis+ Dis- Tot T+ 29 84 113 

T- 4 75 79 Tot 33 159 192  Lower Upper  Value 95% CI 95% CI Se 88.0% 76.9% 99.1% Sp 47.0% 39.2% 54.8% 

PPV 25.7% 17.6% 33.7% NPV 94.9% 90.1% 99.8% 

Comme--2x2 aUS – deused --Uncleused --No exchosen --Good Quality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-105

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

homogeneous or heterogeneous echogenic structure present or when an irregular thickened > 3 mm wall or septum present. Color Doppler imaging RI < 0.4, PI ≤ 1 or a PI ≤

0.8 CA-125: 35 and 65U/ml 
D-106

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommGuerriero, Alcazar, Coccia, et al., 2002 #2130 

Geographical location: Italy Dates: Apr 1997 to Jul 

2000 Size of population: 789 women with 826 masses OtherCase series Reference standard: Pathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: Z statistic K statistic for agreement Blinding: NR Definition of positive and negative on screening test: TV sonography: multiloculated, complex or solid mass in which the echo architecture was not highly indicative of a benign histologic type was categorized as malignant. Color Doppler: 

Age: Mean (SD): 40 (14) Range: 14-81 Menopausal status (n [%]): Pre (< 45): 617 (78%) Post (> 55): 172 (22%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: All women scheduled for surgery in the presence of a persistent adnexal massExclusion criteria: Women with an anechoic unilocular or bilocular cystic mass with a thin regular wall without endocystic vegetation 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Transvaginal sonography: Premenopausal 

 Dis+ Dis- Tot T+ 48 62 110 

T- 1 506 507 Tot 49 568 617  Lower Upper  Value 95% CI 95% CI Se 98.0% 94.1% 100.0%Sp 89.0% 86.4% 91.6% 

PPV 43.6% 34.4% 52.9% NPV 99.8% 99.4% 100.0%

2) Transvaginal sonography: Postmenopausal 

 Dis+ Dis- Tot T+ 91 84 175 

T- 0 88 88 Tot 91 172 263  Lower Upper  Value 95% CI 95% CI Se 100.0% 96.7% 100.0%Sp 51.0% 43.5% 58.5% 

PPV 52.0% 44.6% 59.4% NPV 100.0% 96.6% 100.0%

3) Color Doppler – Premenopausal 

 Dis+ Dis- Tot T+ 46 23 69 

T- 3 545 548 Tot 49 568 617  Lower Upper  Value 95% CI 95% CI Se 94.0% 87.4% 100.0%Sp 96.0% 94.4% 97.6% 

PPV 66.7% 55.5% 77.8% NPV 99.5% 98.8% 100.0%

Comme--CA-12present--EstimindividudenomiQuality ReferenVerificaTest reSample StatisticBlindingDefinitio -; not d
D-107

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

malignancy was assumed if arterial flow was visualized in an echogenic structure or in an irregular solid portion defined as malignant on B-mode imaging. 

4) Color Doppler: Postmenopausal 

 Dis+ Dis- Tot T+ 87 40 127 

T- 4 132 136 Tot 91 172 263  Lower Upper  Value 95% CI 95% CI Se 96.0% 92.0% 100.0%Sp 77.0% 70.7% 83.3% 

PPV 68.5% 60.4% 76.6% NPV 97.1% 94.2% 99.9% 

5) Color Doppler: combined ages 

 Dis+ Dis- Tot T+ 133 63 196 

T- 7 677 684 Tot 140 740 880  Lower Upper  Value 95% CI 95% CI Se 95.0% 91.4% 98.6% Sp 91.5% 89.5% 93.5% PPV 67.9% 61.3% 74.4% NPV 99.0% 98.2% 99.7% 

6) US morphology – combined ages 

 Dis+ Dis- Tot T+ 139 146 285 T- 1 594 595 Tot 140 740 880  Lower Upper  Value 95% CI 95% CI Se 99.3% 97.9% 100.0%Sp 80.3% 77.4% 83.1% PPV 48.8% 43.0% 54.6% NPV 99.8% 99.5% 100.0%
D-108

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommHata, Hata, and Kitao, 1995 #10960 

Geographical location: Japan Dates: NR 

Size of population: 102 Case series

Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Not really Statistical tests used: Se, Sp, Kappa statistic Chi square Blinding: NR Definition of positive and negative on screening test: US morphology : “features that suggested the possibility of malignancy” such as dense irregular septa, multilocular cysts, papillary formation, poorly defined borders, solid focus, echogenic core R< 0.72 PSV > 16 cm/sec 

Age: Mean: 46.1 Range: 20-78 Menopausal status (n [%]): NR Race/ethnicity (n [%]): Japanese Risk factors (n [%]): NR Inclusion criteria: Referred to hospital with mass who had US prior to surgical evaluation Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Peak systolic velocity > 16 cm/sec 

 Dis+ Dis- Tot T+ 25 6 31 

T- 5 66 71 Tot 30 72 102  Lower Upper  Value 95% CI 95% CI Se 83.3% 70.0% 96.6% Sp 91.7% 85.3% 98.1% 

PPV 80.6% 66.7% 94.6% NPV 93.0% 87.0% 98.9% 

2) RI <0.72 

 Dis+ Dis- Tot T+ 28 23 51 

T- 2 49 51 Tot 30 72 102  Lower Upper  Value 95% CI 95% CI Se 93.3% 84.4% 100.0%Sp 68.1% 57.3% 78.9% 

PPV 54.9% 41.2% 68.6% NPV 96.1% 90.8% 100.0%

3) US morphology 

 Dis+ Dis- Tot T+ 26 22 48 

T- 4 50 54 Tot 30 72 102  Lower Upper  Value 95% CI 95% CI Se 86.7% 74.5% 98.9% Sp 69.4% 58.8% 80.0% 

PPV 54.2% 40.1% 68.3% NPV 92.6% 85.6% 99.6% 

Comme--US mscoring --Uncleor PSV --LMP tmaligna--TVUS Quality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-109

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommHata, Hata, Manabe, et al., 1992 #5010 

Geographical location: Japan Dates: NR 

Size of population: 63 Other Prospective series Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: CA-125 – yes RI - no Statistical tests used: ROC curves T tests, Chi-square Blinding: NR Definition of positive and negative on screening test: CA-125 > 35 U/ml RI – calculated from own analysis of data < 0.72 US – not described MRI – malignant = size > 4 cm and (any of the following): 1) cystic, wall > 3 mm +/- nodularity 2) predom solid lesion 3) involvement of other organs or sidewalls or 

Age: Mean: 47.4 Range: 20-78 Menopausal status (n [%]): Pre (< 45): 35 (56%) Post (> 55): 28 (44%) Race/ethnicity (n [%]): JapaneseRisk factors (n [%]): NR Inclusion criteria: Suspected pelvic tumors Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) RI < 0.72 

 Dis+ Dis- Tot T+ 25 17 42 

T- 2 19 21 Tot 27 36 63  Lower Upper  Value 95% CI 95% CI Se 92.6% 82.7% 100.0%Sp 52.8% 36.5% 69.1% 

PPV 59.5% 44.7% 74.4% NPV 90.5% 77.9% 100.0%

2) US 

 Dis+ Dis- Tot T+ 23 11 34 

T- 4 25 29 Tot 27 36 63  Lower Upper  Value 95% CI 95% CI Se 85.2% 71.8% 98.6% Sp 69.4% 54.3% 84.5% 

PPV 67.6% 51.9% 83.4% NPV 86.2% 73.7% 98.8% 

3) MRI 

 Dis+ Dis- Tot T+ 18 1 19 

T- 9 35 44 Tot 27 36 63  Lower Upper  Value 95% CI 95% CI Se 66.7% 48.9% 84.5% Sp 97.1% 91.6% 100.0%

PPV 94.7% 84.7% 100.0%NPV 79.5% 67.6% 91.5% 

4) CA-125 > 35 

Comme--Uncle--Bordemaligna--No US means describ--MRI a--RI cut analysis --UnablQuality ReferenVerificaTest reSample StatisticBlindingDefinitio+/- 
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

omental dz or ascites or adenopathy 

 Dis+ Dis- Tot T+ 16 3 19 

T- 11 33 44 Tot 27 36 63  Lower Upper  Value 95% CI 95% CI Se 59.3% 40.8% 77.8% Sp 91.7% 82.7% 100.0%

PPV 84.2% 67.8% 100.0%NPV 75.0% 62.2% 87.8% 

Herrmann Jr., Locher, and Goldhirsch, 1987 #6840 

Geographical location: Germany Dates: 1981-1985 

Size of population: 312/404 Screening studyRetrospective series Reference standard: Pathology Reference standard applied to all test negatives?: Yes Test reliability established?: No Statistical tests used: Chi-square Blinding: NR Definition of positive and negative on 

Age: NR Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: NR Exclusion criteria: Very young age Pregnancy Endocrinologic disorder Recurrent tumors No pathology diagnosis 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) US (borderline tumors excluded) 

 Dis+ Dis- Tot T+ 38 8 46 

T- 14 177 191 Tot 52 185 237  Lower Upper  Value 95% CI 95% CI Se 73.1% 61.0% 85.1% Sp 95.7% 92.7% 98.6% PPV 82.6% 71.7% 93.6% NPV 92.7% 89.0% 96.4% 

2) US (borderline tumors considered benign) 

 Dis+ Dis- Tot T+ 38 11 49 T- 14 178 192 Tot 52 189 241  Lower Upper  Value 95% CI 95% CI Se 73.1% 61.0% 85.1% Sp 94.2% 90.8% 97.5% PPV 77.6% 65.9% 89.2% NPV 92.7% 89.0% 96.4% 

Comme--Excludget opesonograto test r--Bordefrom aureporte--Data rversus benign togethenumberwith coand NP--Data pprevaleneed ad2x2. --Very uUS scoal (not wdescribQuality ReferenVerificaTest reSample StatisticBlinding
D-111

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

screening test: Ultrasound: Thick septae, irregular solid parts within a mass, indefinite margins, and the presence of ascites and matted bowel loops regarded as malignant. 

Definitio

Hillaby, Aslam, Salim, et al., 2004 #1620 

Geographical location: London, UK Dates: Apr 2000 – Jun 

2003 Size of population: 119 women Case series

Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Interobserver reliability for 2 examiners on 15 cases showed agreement for crescent sign Statistical tests used: Se, Sp Blinding: Yes (prospective study) Definition of positive and negative on screening test: 

Age: Mean: 43 Range: 15-81 Menopausal status (n [%]): Pre: 70 (70%) Post: 30 (30%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Scheduled to undergo surgery for adnexal pathology, referred to tertiary referral gyn scanning unit Exclusion criteria: None 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) US – ovarian crescent sign (T+ = negative) 

 Dis+ Dis- Tot T+ 23 18 41 

T- 1 58 59 Tot 24 76 100  Lower Upper  Value 95% CI 95% CI Se 96.0% 88.2% 100.0%Sp 76.0% 66.4% 85.6% 

PPV 56.1% 40.9% 71.3% NPV 98.3% 95.0% 100.0%

2) PI < 1.0 

 Dis+ Dis- Tot T+ 14 8 22 

T- 10 68 78 Tot 24 76 100  Lower Upper  Value 95% CI 95% CI Se 58.0% 38.3% 77.7% Sp 89.0% 82.0% 96.0% 

PPV 63.6% 43.5% 83.7% NPV 87.2% 79.8% 94.6% 

3) CA-125 ≥ 35 U/ml 

 Dis+ Dis- Tot T+ 21 26 47 

T- 3 50 53 Tot 24 76 100 

Quality ReferenVerificaTest resign evin 15 caSample StatisticBlindingDefinitio
D-112

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

Yes Ovarian crescent sign – presence of normal ovarian tissue on TVUS: Criteria to identify normal ovarian tissues were: Hypoechogenic tissue with or without ovarian follicles located adjacent to the cyst wall, which could not be separated from the cyst by applying a moderate amount of pressure and which was enclosed within the ovarian capsule encircling the tumor. Also CA-125 ≥ 35 U/ml 

PI < 1.0 

 Lower Upper  Value 95% CI 95% CI Se 88.0% 75.0% 100.0%

Sp 66.0% 55.3% 76.7% 

PPV 44.7% 30.5% 58.9% NPV 94.3% 88.1% 100.0%

4) Tumor volume ≥ 180 mL 

 Dis+ Dis- Tot T+ 19 35 54 

T- 5 41 46 Tot 24 76 100  Lower Upper  Value 95% CI 95% CI Se 79.0% 62.7% 95.3% Sp 54.0% 42.8% 65.2% 

PPV 35.2% 22.4% 47.9% NPV 89.1% 80.1% 98.1% 

5) Papillary proliferations 

 Dis+ Dis- Tot T+ 10 10 20 

T- 14 66 80 Tot 24 76 100  Lower Upper  Value 95% CI 95% CI Se 41.0% 21.3% 60.7% Sp 87.0% 79.4% 94.6% 

PPV 50.0% 28.1% 71.9% NPV 82.5% 74.2% 90.8% 

6) Time-averaged maximum velocity (TAMXV ≥ 12 cm/s) 

 Dis+ Dis- Tot T+ 15 7 22 

T- 9 69 78 Tot 24 76 100  Lower Upper 
D-113

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

 Value 95% CI 95% CI Se 63.0% 43.7% 82.3% Sp 91.0% 84.6% 97.4% 

PPV 68.2% 48.7% 87.6% NPV 88.5% 81.4% 95.6% 

Hogdall, Hogdall, Tingulstad, et al., 2000 #2610 

Geographical location: Denmark Dates: Sep 1994 to Apr 

1996 Size of population: 168 Screening study Prospective series Reference standard: Pathology Reference standard applied to all test negatives?: Yes Test reliability established?: ? Interassay coefficient? Statistical tests used: ROC curves Mann-Witney Spearman-Rank Blinding: NR Definition of positive and negative on screening test: Not pre-specified but present Table 3 with 

Age: Benign Median: 48 Range: 19-86 Non-ovarian cancer Median: 69 Range:42-79 Ovarian cancer Median:61.5 Range:31-82 Menopausal status (n [%]): NRRace/ethnicity (n [%]): Danish? Risk factors (n [%]): NR Inclusion criteria: Presence of a pelvic mass and a decision taken to proceed with surgical exploration Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR

1) Overall sensitivity for CA-125 using a cutpoint of 35U/ml 

 Dis+ Dis- Tot T+ 34 28 62 

T- 10 96 106 Tot 44 124 168  Lower Upper  Value 95% CI 95% CI Se 77.3% 64.9% 89.7% Sp 77.4% 70.0% 84.8% 

PPV 54.8% 42.5% 67.2% NPV 90.6% 85.0% 96.1% 

Comme--Data aage 50, that this with ovaspecificQuality ReferenVerificaTest reSample StatisticBlindingDefinitio - 
D-114

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

”generally accepted cutpoints” 

Hricak, Chen, Coakley, et al., 2000 #2800 

Geographical location: San Francisco, CA University Hospital Dates: Apr 1993 – May 

1996 Size of population: 128 women (187 masses) Other Consecutive patients referred for MRI from gynecologist who had surgery Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes; inter- and intraobserver variability explicitly measured Statistical tests used: Logistic regression ROC curves Se, Sp Kappa Blinding: 

Yes

Definition of positive and negative on 

Age: Mean: 53 Range: 18-83 Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Women with diagnosis of adnexal mass referred for MR from Gynoncol clinic who subsequently underwent surgery Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: Compared gadolinium enhanced MRI versus not enhanced 

1) Non-enhanced MRI 

 Dis+ Dis- Tot T+ 83 23 106 

T- 13 68 81 Tot 96 91 187  Lower Upper  Value 95% CI 95% CI Se 86.5% 79.6% 93.3% Sp 74.7% 65.8% 83.7% PPV 78.3% 70.5% 86.1% NPV 84.0% 76.0% 91.9% 

2) Gadolinium-enhanced MRI 

 Dis+ Dis- Tot T+ 91 19 110 T- 5 72 77 Tot 96 91 187  Lower Upper  Value 95% CI 95% CI Se 94.8% 90.3% 99.2% Sp 79.1% 70.8% 87.5% PPV 82.7% 75.7% 89.8% NPV 93.5% 88.0% 99.0% 

Comme--LMP tmaligna--Refergynecomalignasicker p--Data cmass, nQuality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-115

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

screening test: [From ref 19] Malignant = at least one of the following primary criteria present: > 4 cm, bilateral, predominantly solid, cystic with wall or septum > 3 mm or papillary projections. OR at least 2 of the following secondary criteria present: ascites, peritoneal metastasis, adenopathy. 

Huber, Medl, Baumann, et al., 2002 #5700 

Geographical location: Austria Dates: May 1995 – Jan 

2001 Size of population: 93 Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: No Statistical tests used: Chi square Fisher exact test Blinding: Yes Definition of positive and negative on 

Age: NR Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Patients suspected of having ovarian cancer in time frame referred for surgery and had imaging done Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) US morphology 

 Dis+ Dis- Tot T+ 54 8 62 

T- 9 22 31 Tot 63 30 93  Lower Upper  Value 95% CI 95% CI Se 85.0% 76.2% 93.8% Sp 73.0% 57.1% 88.9% 

PPV 87.1% 78.8% 95.4% NPV 71.0% 55.0% 86.9% 

2) MRI 

 Dis+ Dis- Tot T+ 56 4 60 

T- 7 26 33 Tot 63 30 93  Lower Upper  Value 95% CI 95% CI Se 89.0% 81.3% 96.7% Sp 86.0% 73.6% 98.4% 

PPV 93.3% 87.0% 99.6% NPV 78.8% 64.8% 92.7% 

Comme--Patienof ovariinciden--Unclecriteria scoring --CombUS (unafor eachQuality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-116

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

screening test: US – “detection of complex (noncystic) and/or solid mass, which was ≥ 5 cm in premenopausal woman or any size in postmenopausal woman. MRI – descriptive 

Hurteau, Woolas, Jacobs, et al., 1995 #4060 

Geographical location: Patients from London, UK Dates: NR 

Size of population: Unclear – article mentions 100 patients preop evaluation as well as 88 “healthy subjects”, but analysis done on 92 Other Series in single center Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: Sen, Sp Student’s t test Blinding: NR – prospective sampling 

Age: NR Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Unclear – preop with diagnosis of adnexal massExclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) CA-125 > 35 

 Dis+ Dis- Tot T+ 32 31 63 

T- 7 30 37 Tot 39 61 100  Lower Upper  Value 95% CI 95% CI Se 82.1% 70.0% 94.1% Sp 49.2% 36.6% 61.7% PPV 50.8% 38.4% 63.1% NPV 81.1% 68.5% 93.7% 

Comme--Very uinclusio(numbeexplana92) --Data o2x2 tabtest --Inclusnecessdiagnostest Quality ReferenVerificaTest rediscussestablisSample StatisticBlindingDefinitio
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

Definition of positive and negative on screening test: CA-125 > 35 U/mL 

Inoue, Fujita, Nakazawa, et al., 1992 #5120 

Geographical location: Osaka, Japan University Hospital Dates: Sep 1989 – May 

1991 Size of population: 382 women Other Patents who underwent surgery for adnexal mass Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: ROC curves Se, Sp Blinding: 

NoDefinition of positive and negative on screening test: CA-125 > 65 U/mL CEA > 2.4 ng/mL 

Age: NR Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Women undergoing surgery for (presumed) adnexal mass at one of the University hospitals in time frame Exclusion criteria: LMP tumors other than those of surface epithelialstromal type and nongynecological tumors. 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: None 

1) CA-125 (> 65 U/mL) 

 Dis+ Dis- Tot T+ 25 44 69 

T- 40 273 313 Tot 65 317 382  Lower Upper  Value 95% CI 95% CI Se 38.0% 26.2% 49.8% Sp 86.0% 82.2% 89.8% 

PPV 36.2% 24.9% 47.6% NPV 87.2% 83.5% 90.9% 

2) CEA 

 Dis+ Dis- Tot T+ 14 10 24 

T- 51 307 358 Tot 65 317 382  Lower Upper  Value 95% CI 95% CI Se 22.0% 11.9% 32.1% Sp 97.0% 95.1% 98.9% 

PPV 58.3% 38.6% 78.1% NPV 85.8% 82.1% 89.4% 

Additional data reported for other markers, Sialyl-Tn (STN), sialys-Lewis Xi (SLX), CA 19-9, Tissue polypeptide antigen 

Comme--CA-12--No deat all --5 surfwere grcategorQuality ReferenVerificaTest rediscussbetweeSample StatisticBlindingDefinitio
D-118

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommItakura, Kikkawa, Kajiyama, et al., 2003 #1690 

Geographical location: Japan University Hospital Dates: Jun 1998 – Jul 

2000 Size of population: 84 women (95 tumors) Other Hospital referral for surgery secondary to mass Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: CA-125 – yes DePriest – yes PI - yes Statistical tests used: Se, Sp Blinding: Prospective study – blinding not discussed Definition of positive and negative on screening test: CA-125 > 65 U/mL Morphological index of DePriest score > 7 PI < 1.0 

Age: Mean (SD): 49.1 Menopausal status (n [%]): Pre: 41 (48.8%) Post : 43 (51.2%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Patients who underwent surgery at university hospital for mass (not clearly described) Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Morphological index of DePriest (> 7) 

 Dis+ Dis- Tot T+ 24 15 39 

T- 3 42 45 Tot 27 57 84  Lower Upper  Value 95% CI 95% CI Se 90.3% 79.1% 100.0%Sp 73.4% 61.9% 84.9% 

PPV 61.5% 46.3% 76.8% NPV 93.3% 86.0% 100.0%

2) PI (min < 1.0) 

 Dis+ Dis- Tot T+ 22 8 30 

T- 5 49 54 Tot 27 57 84  Lower Upper  Value 95% CI 95% CI Se 80.6% 65.7% 95.5% Sp 85.9% 76.9% 94.9% 

PPV 73.3% 57.5% 89.2% NPV 90.7% 83.0% 98.5% 

3) CA-125 (> 65 U/ml) 

 Dis+ Dis- Tot T+ 19 7 26 

T- 8 50 58 Tot 27 57 84  Lower Upper  Value 95% CI 95% CI Se 70.4% 53.2% 87.6% Sp 87.7% 79.2% 96.2% 

PPV 73.1% 56.0% 90.1% NPV 86.2% 77.3% 95.1% 

Comme--Se anpatient tumor) --CA-12--BordemalignaQuality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-119

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommJacobs, Oram, Fairbanks, et al., 1990 #6820 

Geographical location: London Dates: NR 

Size of population: 143 Other Consecutive series Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: CA-125 - yes Statistical tests used: Stepwise logistic regression Se, Sp RMI Blinding: NR – but prospective Definition of positive and negative on screening test: CA-125 > 30U/mL US: 1 point assigned for each of the following: --multilocular cyst --solid areas --metastases --ascites --bilateral lesion 

Age: Mean (SD): Benign 48.8 (14.3) Malignant 59.0 (11.8) Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Consecutive admissions for elective surgical investigation of pelvic mass in hospital in time frame Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) CA-125 > 30 

 Dis+ Dis- Tot T+ 34 25 59 

T- 8 76 84 Tot 42 101 143  Lower Upper  Value 95% CI 95% CI Se 81.0% 69.1% 92.9% Sp 75.0% 66.6% 83.4% 

PPV 57.6% 45.0% 70.2% NPV 90.5% 84.2% 96.8% 

2) US score > 1 

 Dis+ Dis- Tot T+ 41 52 93 

T- 0 46 46 Tot 41 98 139  Lower Upper  Value 95% CI 95% CI Se 100.0% 92.7% 100.0%Sp 46.9% 37.0% 56.8% 

PPV 44.1% 34.0% 54.2% NPV 100.0% 93.5% 100.0%

3) US score > 2 

 Dis+ Dis- Tot T+ 29 17 46 

T- 12 81 93 Tot 41 98 139  Lower Upper  Value 95% CI 95% CI Se 70.7% 56.8% 84.6% Sp 82.7% 75.2% 90.2% 

PPV 63.0% 49.1% 77.0% NPV 87.1% 80.3% 93.9% 

Comme--CA-12Quality ReferenVerificaTest reSample StatisticBlindingDefinitio(but didas cuto
D-120

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommJacobs, Stabile, Bridges, et al., 1988 #6830 

Geographical location: London, UK Dates: NR 

Size of population: 1010 screened with BME and CA-125 58 US done secondary to abnormal BME or CA125 9 went to surgery Screening study Reference standard: Surgery for 9 repeat US and BME at 3 month intervals for one year for initial abnormals (by CA125 or BME) Reference standard applied to all test negatives?: No Test reliability established?: Yes Statistical tests used: Se, Sp Blinding: NR

Definition of positive and negative on screening test: BME – “palpable mass of any size . . . separate from uterus or GI tract” CA-125 ≥ 30 U/ml 

US ovarian volume > 8.8ml 

Age: Mean: 54 Range: 45-83 Menopausal status (n [%]): Post (> 55): 1010 (100%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: NR Exclusion criteria: 

NR 

Symptomatic (n [%]): 0 (0%) Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) CA-125 > 30 U/ml (assuming all test negatives truly negative) 

 Dis+ Dis- Tot T+ 1 30 31 

T- 0 979 979 Tot 1 1009 1010  Lower Upper  Value 95% CI 95% CI Se 100.0% 

-

200.0% 100.0%

Sp 97.0% 96.0% 98.1% PPV 3.2% 0.0% 9.4% NPV 100.0% 99.7% 100.0%

2) CA-125 > 30U/ml not assuming test negatives true negative (including only those which had US) 

 Dis+ Dis- Tot T+ 1 30 31 T- 0 27 27 Tot 1 57 58  Lower Upper  Value 95% CI 95% CI Se 100.0% 

-

200.0% 100.0%

Sp 47.4% 34.4% 60.3% PPV 3.2% 0.0% 9.4% NPV 100.0% 88.9% 100.0%

3) BME (assuming all negatives true negative) 

 Dis+ Dis- Tot T+ 1 27 28 T- 0 982 982 Tot 1 1009 1010  Lower Upper  Value 95% CI 95% CI Se 100 0%

-

200 0% 100.0%

Comme--Unclevolume from --Vague --Low inscreeni--AbdomQuality ReferenVerificaTest reSample StatisticBlindingDefinitio
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

200.0%

Sp 97.3% 96.3% 98.3% PPV 3.6% 0.0% 10.4% NPV 100.0% 99.7% 100.0%

4) BME not assuming test negatives true negative 

 Dis+ Dis- Tot T+ 1 27 28 T- 0 30 30 Tot 1 57 58  Lower Upper  Value 95% CI 95% CI Se 100.0% 

-

200.0% 100.0%

Sp 52.6% 39.7% 65.6% PPV 3.6% 0.0% 10.4% NPV 100.0% 90.0% 100.0%

4) US alone (ovarian volume > 8.8ml) 

 Dis+ Dis- Tot T+ 1 12 13 T- 0 45 45 Tot 1 57 58  Lower Upper  Value 95% CI 95% CI Se 100.0% 

-

200.0% 100.0%

Sp 78.9% 68.4% 89.5% PPV 7.7% 0.0% 22.2% NPV 100.0% 93.3% 100.0%
D-122

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommJain, 1994 #4620 

Geographical location: Stanford, CA Dates: NR 

Size of population: 42 women (50 masses) Other Prospective series of surgical cases with US Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: RI – yes US – not really (references his own article the next in this batch #4950) Statistical tests used: NR Blinding: NR – but prospective Definition of positive and negative on screening test: RI < 0.4 Grey scale US – Presence of any of the following: Irregular solid portion, irregular wall, thick irregular septa, mural notdule; Doppler done, 

Age: Mean: 43 Range: 33-55 Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: 42 women with clinically suspected adnexal masses undergoing surgery – US performed 1-5 days prior Exclusion criteria: Obstetrical cases 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) RI < 0.4 of MASSES 

 Dis+ Dis- Tot T+ 7 7 14 

T- 2 33 35 Tot 9 40 49  Lower Upper  Value 95% CI 95% CI Se 77.8% 50.6% 100.0%Sp 82.5% 70.7% 94.3% PPV 50.0% 23.8% 76.2% NPV 94.3% 86.6% 100.0%

2) US (MASSES) 

 Dis+ Dis- Tot T+ 9 2 11 T- 0 38 38 Tot 9 40 49  Lower Upper  Value 95% CI 95% CI Se 100.0% 66.7% 100.0%Sp 95.0% 88.2% 100.0%PPV 81.8% 59.0% 100.0%NPV 100.0% 92.1% 100.0%

Comme--Data pcould banalysis --Uncledid US --No disoperato--Data pnot patiQuality ReferenVerificaTest reSample StatisticBlindingDefinitio
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

but neovascularization not required for diagnosis of malignancy 

Jain, Friedman, Pettinger, et al., 1993 #4950 

Geographical location: Davis and Palo Alto, CA Dates: NR 

Size of population: 32 Other Prospective series Reference standard: Histopathology or FNA at time of laparoscopy Reference standard applied to all test negatives?: Yes Test reliability established?: MRI - Statistical tests used: Kappa, Se, Sp Blinding: NR – but prospective Definition of positive and negative on screening test: Descriptive diagnostic criteria for both MRI and US – “simple cyst, hem cyst, endometrioma, dermoid, pedunc fibroid, ovarian carcinoma, ovarian torsion” 

Age: Mean: 41.5 Range: 29-54 Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Prospective women with suspected masses at hospital scheduled for surgery Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) US: Cancer vs. benign 

 Dis+ Dis- Tot T+ 3 14 17 

T- 0 20 20 Tot 3 34 37  Lower Upper  Value 95% CI 95% CI Se 100.0% 0.0% 100.0%Sp 60.0% 43.5% 76.5% 

PPV 17.6% 0.0% 35.8% NPV 100.0% 85.0% 100.0%

2) MRI: Cancer vs. benign 

 Dis+ Dis- Tot T+ 2 0 2 

T- 1 34 35 Tot 3 34 37  Lower Upper  Value 95% CI 95% CI Se 67.0% 13.8% 100.0%Sp 100.0% 91.2% 100.0%

PPV 100.0% 0% 100.0%NPV 97.1% 91.6% 100.0%

Comme--Kappa --Unclestudy (i--US scdid MR--Patholaproscexamin--Se/Sp patients Quality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-124

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommJuhasz, Kurjak, Lampe, et al., 1990 #10860 

Geographical location: Yugoslavia and Hungary Dates: NR 

Size of population: 147 Case series Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: Se, Sp Blinding: NR Definition of positive and negative on screening test: Presence or absence of color flow within adnexal mass on Doppler 

Age: NR Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: NR Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Color flow present or absent 

 Dis+ Dis- Tot T+ 21 17 38 

T- 1 108 109 Tot 22 125 147  Lower Upper  Value 95% CI 95% CI Se 95.5% 86.8% 100.0%Sp 86.4% 80.4% 92.4% PPV 55.3% 39.5% 71.1% NPV 99.1% 97.3% 100.0%

Comme--Unclepresent --No decharact--TVUS Quality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-125

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommKawahara, Yoshida, Kurokawa, et al., 2004 #10 

Geographical location: Fukui, Japan Dates: Sept 2001 – Aug 

2003 Size of population: 38 Other Series of suspected ovarian cancer cases who went to surgery Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: MRI – yes PET scan - ? Statistical tests used: Se, Sp Blinding: NR – prospective study Definition of positive and negative on screening test: MRI – if any of these features was met, mass considered suspicious for malignancy: “cystic without solid areas, diameter of 4cm or less, wall thickness < 0.3 cm, the presence of typical characteristics of 

Age: NR Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Patients who had been screened in gynecological oncology clinic with BME and US and considered to have masses suspicious for malignancy Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) MRI 

 Dis+ Dis- Tot T+ 21 2 23 

T- 2 13 15 Tot 23 15 38  Lower Upper  Value 95% CI 95% CI Se 91.3% 79.8% 100.0%Sp 86.7% 69.5% 100.0%PPV 91.3% 79.8% 100.0%NPV 86.7% 69.5% 100.0%

2) FDG-PET 

 Dis+ Dis- Tot T+ 18 0 18 T- 5 15 20 Tot 23 15 38  Lower Upper  Value 95% CI 95% CI Se 78.3% 61.4% 95.1% Sp 100.0% 80.0% 100.0%PPV 100.0% 83.3% 100.0%NPV 75.0% 56.0% 94.0% 

Comme--LMP tmaligna--Patienreprese--MRI sreprodu--No disobserve--In repstate “thcorrectlmalignabenign 15 patieQuality ReferenVerificaTest reSample StatisticBlindingDefinitio
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

dermoid cyst or endometrioma” For PET scan with 18-Flourodeoxyglucose – “hypermetabolic lesions that were more intense than the liver and not attributable to bladder etc. were considered positive for malignancy” 

Kawai, Kikkawa, Ishikawa, et al., 1994 #10940 

Geographical location: Japan Dates: Apr 1990 – Aug 

1993 Size of population: 109 Case series Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: Student’s t test Chi square analysis Blinding: NR Definition of positive and negative on screening test: 

Age: NR Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: NR Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Doppler 

 Dis+ Dis- Tot T+ 30 14 44 

T- 10 55 65 Tot 40 69 109  Lower Upper  Value 95% CI 95% CI Se 75.0% 61.6% 88.4% Sp 79.2% 69.6% 88.8% 

PPV 68.2% 54.4% 81.9% NPV 84.6% 75.8% 93.4% 

2) CA-125 > 35U/ml 

 Dis+ Dis- Tot T+ 29 37 66 

T- 11 32 43 Tot 40 69 109  Lower Upper  Value 95% CI 95% CI Se 72.2% 58.3% 86.1% Sp 45.8% 34.0% 57.6% 

PPV 43.9% 32.0% 55.9% NPV 74.4% 61.4% 87.5% 

3) CA-72-4 

 Dis+ Dis- Tot T+ 17 12 29 

T- 23 57 80

Comme--Meanis unus--Cut pounusua--LMP tmaligna--Calcuslightly --TVUS Quality ReferenVerificaTest reSample StatisticBlindingDefinitio
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

Doppler: 1/PI with cutoff 0.8 (which equals a cutoff for PI of 1.25) CA-125 > 35 U/ml CA-72-4 > 4U/ml CA-19-9 > 37U/ml 

Tot 40 69 109 

 Lower Upper  Value 95% CI 95% CI Se 41.7% 26.4% 57.0% Sp 83.3% 74.5% 92.1% 

PPV 58.6% 40.7% 76.5% NPV 71.3% 61.3% 81.2% 

4) CA-19-9 

 Dis+ Dis- Tot T+ 14 12 26 

T- 26 57 83 Tot 40 69 109  Lower Upper  Value 95% CI 95% CI Se 36.1% 21.2% 51.0% Sp 83.3% 74.5% 92.1% 

PPV 53.8% 34.7% 73.0% NPV 68.7% 58.7% 78.7% 
D-128

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommKomatsu, Konishi, Mandai, et al., 1996 #4050 

Geographical location: Kyoto, Japan Dates: May 1989 – May 

1993 Size of population: 82 Other Retrospective case series comparing US and MR Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Statistical tests used: Blinding: Yes Definition of positive and negative on screening test: US classification: 0 = cyst with welldefined, thin wall 1a = septation 1b = solid tissue 2a = complex mass with internal structure with diffuse low-level echoes, no distinct findings of cyst 2b = complex mass with internal structure with 

Age: Mean: 45.9 Range: 17-89 Menopausal status (n [%]): Pre (< 45): 54 (65.9%) Post (> 55): 28 (34.1%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: NR Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) US: benign vs. malignant (US class 0 or 1a benign, all other malignant); borderline counted as malignancy 

 Dis+ Dis- Tot T+ 34 26 60 

T- 0 22 22 Tot 34 48 82  Lower Upper  Value 95% CI 95% CI Se 100.0% 91.2% 100.0%Sp 45.8% 31.7% 59.9% PPV 56.7% 44.1% 69.2% NPV 100.0% 86.4% 100.0%

2) MRI: benign vs. malignant (MRI class 1b malignant, all others benign); borderline counted as malignancy 

 Dis+ Dis- Tot T+ 31 3 34 T- 3 22 25 Tot 34 25 59  Lower Upper  Value 95% CI 95% CI Se 91.2% 81.6% 100.0%Sp 88.0% 75.3% 100.0%PPV 91.2% 81.6% 100.0%NPV 88.0% 75.3% 100.0%

Comme--Unclestudy (c--Clinica--Outcoundergo --Over maligna--Resulage/meQuality ReferenVerificanot undTest redescribSample StatisticpresentBlindingDefinitio
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

excrescences with lowlevel echoes and blurred margin 1b, 2a, 2b considered possibly malignant MRI: 0 = cyst with well-defined wall, no internal enhancement, homogenous low intensity on T-1 weighted images, high intensity on T2 1a = neoplasm with septation 1b = solid 2a = cystic mass with complex fluid such as blood, proteinaceous fluid, or fat 2b = cystic mass with unenhanced excrescences 1b considered possibly malignant 
D-130

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommKurjak and Kupesic, 1999 #2920 

Geographical location: Zagreb, Croatia University Hospital Dates: Jan 1997 – Jun 

1998 Size of population: 120 women Other Patients scheduled for surgery at university hospital Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: No Statistical tests used: Se, Sp Blinding: No – but prospective Definition of positive and negative on screening test: TVUS score ≥ 5 (where 

+2 for papillarities > 3 mm, +1 for shadowing present, +1 for septa > 3 mm, +2 for solid parts present, +2 for mixed or high echogenicity, +1 for peritoneal fluid, +2 for RI ≤ 0.42 

Age: Mean (SD):  Pre 34  Peri 49  Post 61 Range: 18-77 Menopausal status (n [%]): Pre: 76 (63.3%) Peri: 7 (5.8%) Post: 37 (30.8%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Not clearly stated – women with masses to undergo surgery in hospital Premenopausal women had US during early proliferative phase only Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) 2D US combined 

 Dis+ Dis- Tot T+ 10 3 13 

T- 1 106 107 Tot 11 109 120  Lower Upper  Value 95% CI 95% CI Se 90.9% 73.9% 100.0%Sp 97.3% 94.2% 100.0%

PPV 76.9% 54.0% 99.8% NPV 99.1% 97.2% 100.0%

2) 3D US combined 

 Dis+ Dis- Tot T+ 11 1 12 

T- 0 108 108 Tot 11 109 120  Lower Upper  Value 95% CI 95% CI Se 100.0% 72.7% 100.0%Sp 99.1% 97.3% 100.0%

PPV 91.7% 76.0% 100.0%NPV 100.0% 97.2% 100.0%

Comme--TVUS systemno refereliabilitreprodu--Same Quality ReferenVerificaTest reSample StatisticBlindingDefinitio
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

3D US score > 7 (where +2 for papilarities, +1 for present shadowing, +1 for septa >3 mm, +2 for solid parts present, +2 for mixed or high echogenicity, +1 for peritoneal fluid present, +2 for irregular surface, +2 for relation with surrounding structures disturbed, +2 for chaotic vessel arrangement, +2 for complex branching pattern) 

Kurjak, Kupesic, Sparac, et al., 2000 #2560 

Geographical location: Zagreb, Croatia University Hospital Dates: Jan 1998 – Jun 

1999 Size of population: 90 women Other Prospective patients with masses for surgery in university hospital Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: No (although same scale used in articles #2820 or #2920) 

Age: Mean (SD):  Pre – 34  Peri – 49  Post – NR Median: Range: 18-77 Menopausal status (n [%]): Pre: 58 (64.4%) Peri: 4 (4.4%) Post: 28 (31.1%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Prospective patients with ovarian mass scheduled toHave surgery in hospital Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) 2D alone (B-mode) 

 Dis+ Dis- Tot T+ 6 5 11 

T- 3 76 79 Tot 9 81 90  Lower Upper  Value 95% CI 95% CI Se 66.7% 35.9% 97.5% Sp 93.8% 88.6% 99.1% 

PPV 54.5% 25.1% 84.0% NPV 96.2% 92.0% 100.0%

2) 2D Doppler alone RI ≤ 0.42 

 Dis+ Dis- Tot T+ 8 4 12 

T- 1 77 78 Tot 9 81 90  Lower Upper  Value 95% CI 95% CI Se 88.9% 68.4% 100.0%Sp 95.1% 90.3% 99.8% 

PPV 66.7% 40.0% 93.3% NPV 98.7% 96.2% 100.0%

Comme--The sinventeindepenthe liter--Differeassessclear Quality ReferenVerificaTest reSample StatisticBlindingDefinitio+/- 
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

Statistical tests used: Se, Sp Blinding: Yes Definition of positive and negative on screening test: 2D US for 2D alone score ≥ 3 is 

positive for Doppler alone score ≥2 is positive for combined 2D score ≥

5 score is positive where +2 for papillarities, +1 for shadowing present, +1 for septa > 3 mm thick, +2 for solid parts present, +2 for mixed of high level echogenicity, +1 for peritoneal fluid present, +2 for RI ≤ 0.42 

3D US score ≥ 5 is+ for Doppler alone score ≥2+ for combined score ≥

7 where +2 for papillarities, +1 for shadowing present, +1 for septa > 3 mm thick, +2 for solid parts present, +2 for mixed of high level echogenicity, +1 for peritoneal fluid present, +2 for irregular surface, +2 for disturbed relation with surrounding structures, +2 for chaotic vessel arrangement, +2 for complex branching pattern 

3) Combined 2D US and Doppler 

 Dis+ Dis- Tot T+ 8 2 10 

T- 1 79 80 Tot 9 81 90  Lower Upper  Value 95% CI 95% CI Se 88.9% 68.4% 100.0%Sp 97.5% 94.1% 100.0%

PPV 80.0% 55.2% 100.0%NPV 98.8% 96.3% 100.0%

4) 3D TVUS 

 Dis+ Dis- Tot T+ 7 2 9 

T- 2 79 81 Tot 9 81 90  Lower Upper  Value 95% CI 95% CI Se 77.8% 50.6% 100.0%Sp 97.5% 94.1% 100.0%

PPV 77.8% 50.6% 100.0%NPV 97.5% 94.2% 100.0%

5) 3D Doppler 

 Dis+ Dis- Tot T+ 8 2 10 

T- 1 79 80 Tot 9 81 90  Lower Upper  Value 95% CI 95% CI Se 88.9% 68.4% 100.0%Sp 97.5% 94.1% 100.0%

PPV 80.0% 55.2% 100.0%NPV 98.8% 96.3% 100.0%

6) Combined 3D 
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

 Dis+ Dis- Tot T+ 9 1 10 T- 0 80 80 Tot 9 81 90  Lower Upper  Value 95% CI 95% CI Se 100.0% 66.7% 100.0%Sp 98.8% 96.4% 100.0%

PPV 90.0% 71.4% 100.0%NPV 100.0% 96.3% 100.0%

Kurjak and Predanic, 1992 #4990 

Geographical location: Zagreb Croatia University Hospital Dates: Sep 1990 – Sep 

1991 Size of population: 812 women screened with US in whom 174 masses detected in 154 women Other Combination – initially screening of women with “clinical suspicion of mass” then analysis of subset who went to surgery (n = 154) Reference standard: For subset - Histopathology Reference standard applied to all test negatives?: Yes for subset Test reliability 

Age: Mean (SD): 48 Range: 19-76 Menopausal status (n [%]): Pre: 111 (72%) Post: 43 (28%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Initially, all women referred to hospital in time frame with clinical suspicion of adnexal mass. Then those who had mass on US and went to surgery Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): Presumably 100% Detected by imaging (n [%]): Not applicable Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Morphologic scoring system 

 Dis+ Dis- Tot T+ 35 7 42 

T- 3 129 132 Tot 38 136 174  Lower Upper  Value 95% CI 95% CI Se 92.1% 83.5% 100.0%Sp 94.8% 91.1% 98.5% 

PPV 83.3% 72.1% 94.6% NPV 97.7% 95.2% 100.0%

2) Color Doppler scoring system 

 Dis+ Dis- Tot T+ 37 0 37 

T- 1 136 137 Tot 38 136 174  Lower Upper  Value 95% CI 95% CI Se 97.3% 92.1% 100.0%Sp 100.0% 97.8% 100.0%

PPV 100.0% 91.9% 100.0%NPV 99.3% 97.8% 100.0%

3) Combined Doppler and morphology 

Comme--Article system used pr#2560) criteria) --Data anot indiQuality ReferenVerificaTest reSample Statisticany of tBlindingDefinitio
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

established?: No Statistical tests used: Se, Sp Blinding: NR but prospective Definition of positive and negative on screening test: TVUS for 2D alone score ≥ 3 is 

positive for Doppler alone score ≥2 is positive for combined 2D score ≥

5 score is positive where +2 for papillarities, +1 for shadowing present, +1 for septa > 3 mm thick, +2 for solid parts present, +2 for mixed of high level echogenicity, +1 for peritoneal fluid present, +2 for RI ≤ 0.42 

 Dis+ Dis- Tot 

T+ 37 0 37 

T- 1 136 137 Tot 38 136 174  Lower Upper  Value 95% CI 95% CI Se 97.3% 92.1% 100.0%Sp 100.0% 97.8% 100.0%

PPV 100.0% 91.9% 100.0%NPV 99.3% 97.8% 100.0%

Kurjak, Schulman, Sosic, et al., 1992 #5020 

Geographical location: Zagreb, Croatia Dates: 1989-1990 

Size of population: 1000 screened 83 operated on Screening study For N = 83, operative series Reference standard: Histopathology (for N = 83) 

Age: NR Menopausal status (n [%]): Post (> 55): 83 (100%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Age > 40 At least 12 months since 

Symptomatic (n [%]): For N = 1000, 257 (25.7%) were symptomatic For N = 83 of the 29 with malignant tumors, 25 were symptomatics Detected by exam (n [%]): NR Detected by imaging (n [%]): For N = 1000, 83 had US that lead to surgery (8.3%) Combination (n [%]): 

1) For RI < 0.41 

 Dis+ Dis- Tot T+ 28 3 31 

T- 1 51 52 Tot 29 54 83  Lower Upper  Value 95% CI 95% CI Se 96.0% 88.9% 100.0%Sp 95.0% 89.2% 100.0%

PPV 90.3% 79.9% 100.0%NPV 98.1% 94.3% 101.0%

2) US morphology 

Comme--US scillustratdescriband how tested/v--RI cutupon difrom thprior reauthors --Doppldescripto be idthe excmeasur
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

Reference standard applied to all test negatives?: Yes for N = 83 Test reliability established?: Yes Statistical tests used: Chi-square Fisher exact Student t test Se, Sp Blinding: NR – but prospective Definition of positive and negative on screening test: RI < 0.41 US morphology score > 4 (figure 1): Color Doppler score – 0 for vessels not seen, 1 for regular separate vessels, 2 for randomly dispersed vessels 

LMP Criteria for surgery included: Mass 5 cm or greater on at least 2 exams Cyst associated with persistent or acute pain Enlarged ovary or cyst with RI “near” 0.4 on 2 separate Exclusion criteria: NR 

NR Additional data used for diagnosis: NR 

 Dis+ Dis- Tot T+ 14 1 15 

T- 15 53 68 Tot 29 54 83  Lower Upper  Value 95% CI 95% CI Se 48.0% 29.8% 66.2% Sp 98.0% 94.3% 100.0%

PPV 93.3% 80.7% 100.0%NPV 77.9% 68.1% 87.8% 

3) For Doppler score (> 2) 

 Dis+ Dis- Tot T+ 26 1 27 

T- 3 53 56 Tot 29 54 83  Lower Upper  Value 95% CI 95% CI Se 89.7% 78.6% 100.0%Sp 98.1% 94.6% 100.0%PPV 96.3% 89.2% 100.0%NPV 94.6% 88.7% 100.0%

4) For combined US and Doppler (< 6) 

 Dis+ Dis- Tot T+ 26 3 29 T- 3 51 54 Tot 29 54 83  Lower Upper  Value 95% CI 95% CI Se 89.7% 78.6% 100.0%Sp 94.4% 88.3% 100.0%PPV 89.7% 78.6% 100.0%NPV 94.4% 88.3% 100.0%

leading results --No disobserve--Numb--Follownot repoQuality ReferenVerificaseries, Test reSample StatisticBlindingDefinitiofor RI, +
D-136

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommKurjak, Shalan, Kupesic, et al., 1994 #4470 

Geographical location: Zagreb, Croatia Dates: Jan 1988 to Dec 

1992 Size of population: 5013 screened 38 operated on Screening study Reference standard: Histopathology for few who went to surgery Otherwise repeat US Reference standard applied to all test negatives?: No But US repeated in initial abnormals (cycstic structures less than 5cm) followed up after 6 months Test reliability established?: Yes Statistical tests used: NR - proportions Blinding: NR - prospective Definition of positive and negative on screening test: “a persistently enlarged ovary” – 2.5 cm or greater in two separate scans RI < 0.41 

Age: Mean (SD): Pre 45.1 (3.5) Post 56.2 (5.2) Range: 4-71 Menopausal status (n [%]): Pre (< 45): 2214 (44%) Post (> 55): 2799 (56%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Age ≥ 40 

No “pelvic symptoms” Exclusion criteria: 

Women on hormonal therapy 

Symptomatic (n [%]): 0 (0%) Detected by exam (n [%]): 0 (0%) Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: Premenopausal women scanned during day 3-8 of cycle STUDY FLOW – 5013 screened 424 abnormal ovaries, of whom 20 went to surgery, leaving 404 repeat US (316 still pending), of whom 70 resolved spontaneously 18 persistent went to surgery

1) US – persistent mass; only those with surgical confirmation 

 Dis+ Dis- Tot T+ 4 1 5 

T- 0 27 27 Tot 4 28 32  Lower Upper  Value 95% CI 95% CI Se 100.0% 25.0% 100.0%Sp 96.4% 89.6% 100.0%PPV 80.0% 44.9% 100.0%NPV 100.0% 88.9% 100.0%

2) US, assuming all test negative true negatives, excluding 316 with results not reported 

 Dis+ Dis- Tot T+ 4 1 5 T- 0 97 97 Tot 4 98 102  Lower Upper  Value 95% CI 95% CI Se 100.0% 25.0% 100.0%Sp 99.0% 97.0% 100.0%PPV 80.0% 44.9% 100.0%NPV 100.0% 96.9% 100.0%

Comme--Decis--Scree316 wostill (frothis is c--Unclediagnoscombinmorpho--US fospan of --Assumdiscuss--No disobserve--Resulage/meQuality ReferenVerificaTest reSample Statistictesting BlindingDefinitio
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

US morphology score > 4 

Kurjak, Zalud, and Alfirevic, 1991 #5190 

Geographical location: Zagreb, Croatia Dates: NR 

Size of population: 14317 total 8,620 asymptomatic for screening 5697 with “suspected adnexal mass” 680 operated on Screening study Reference standard: Histopathology in 680 operated on Reference standard applied to all test negatives?: Only to surgical cases Test reliability established?: Yes Statistical tests used: Not described - proportions Blinding: Not mentioned (prospective) Definition of positive and negative on screening test: RI < 0.4 

Age: Mean: Pre 42 Post 56 Range: 18-72 Menopausal status (n [%]): Pre (< 45): 7495 Post (> 55): 1125 This is of the 8620 women referred from clinic Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: NR Exclusion criteria: NR 

Symptomatic (n [%]): Unclear Detected by exam (n [%]): ?5697/14,317: Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) RI < 0.4 

 Dis+ Dis- Tot T+ 54 1 55 

T- 2 623 625 Tot 56 624 680  Lower Upper  Value 95% CI 95% CI Se 96.4% 91.6% 100.0%Sp 99.8% 99.5% 100.0%PPV 98.2% 94.7% 100.0%NPV 99.7% 99.2% 100.0%

Comme--No methis stu--8620 screenigyn clin(not stamade), analysis --Propomenoparather t--No mewere un--No me--Very pnumber--RI meseparatmeasur--Inter odiscuss--RI < 0use 0.4--Unclesample differen--16/55 Quality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-138

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommKurtz, Tsimikas, Tempany, et al., 1999 #2940 

Geographical location: Ann Arbor, MI Baltimore, MD Boston, MA Philadelphia, PA University Hospitals Dates: May 1993 – Apr 

1996 Size of population: 280 women Other All eligible patients referred by Gyn Onc to University hospital for surgery Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: No Statistical tests used: Se, Sp, ROC Blinding: Yes to outcome (prospective) radiologists not blinded to diagnosis Definition of positive and negative on screening test: 

Age: Mean: 52 Median: 51.5 Range 19-82 Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Over 18, suspected of having ovarian cancer based on physical exam or pelvic US Exclusion criteria: Unable to provide consent, not a surgical candidate, pregnancy, prior surgery within 6 months of entry into study 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Doppler and Conventional US 

 Dis+ Dis- Tot T+ 82 6 88 

T- 27 149 176 Tot 109 155 264  Lower Upper  Value 95% CI 95% CI Se 75.2% 67.1% 83.3% Sp 96.1% 93.1% 99.2% PPV 93.2% 87.9% 98.4% NPV 84.7% 79.3% 90.0% 

2) CT 

 Dis+ Dis- Tot T+ 58 16 74 T- 5 134 139 Tot 63 150 213  Lower Upper  Value 95% CI 95% CI Se 92.1% 85.4% 98.7% Sp 89.3% 84.4% 94.3% PPV 78.4% 69.0% 87.8% NPV 96.4% 93.3% 99.5% 

3) MRI 

 Dis+ Dis- Tot T+ 47 16 63 T- 1 115 116 Tot 48 131 179  Lower Upper  Value 95% CI 95% CI Se 97.9% 93.9% 100.0%Sp 87.8% 82.2% 93.4% PPV 74.6% 63.9% 85.4% NPV 99.1% 97.5% 100.0%

Comme--Data iROC cutotal N’s agree w--ReferoncologQuality ReferenVerificawere exTest reSample StatisticBlindingDefinitio
D-139

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommLeeners, Schild, Funk, et al., 1996 #3940 

Geographical location: Aachen, Germany Academic Dates: Jan 1993 – Sep 

1994 Size of population: 101 patients (109 tumors) 95 women got surgery Other Consecutive series in single center Reference standard: Histopathology for 95 Unclear what for the other 6 Reference standard applied to all test negatives?: No – see above Test reliability established?: 

YesStatistical tests used: Fisher exact Wilcoxon 2 sample test Blinding: NR but prospective Definition of positive and negative on screening test: Sassone’s score > 9 PI < 0.65 RI < 0.45 

Age: Mean: 48.4 Range: 16-84 Menopausal status (n [%]): Pre (< 45): 67 (66.3%) Post (> 55): 34(33.7%) Race/ethnicity (n [%]): NR Risk factors (n [%]): Family history: 16 (15.8%)Inclusion criteria: Consecutive patients referred to US for “clinical suspicion of an adnexal mass” Exclusion criteria: 

NR 

Symptomatic (n [%]): 52 (51.5%) Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Sassone score 

 Dis+ Dis- Tot T+ 16 13 29 

T- 7 73 80 Tot 23 86 109  Lower Upper  Value 95% CI 95% CI Se 69.8% 51.0% 88.5% Sp 85.0% 77.5% 92.5% 

PPV 55.2% 37.1% 73.3% NPV 91.3% 85.1% 97.4% 

2) Doppler (RI – lowest from a series of measurements) 

 Dis+ Dis- Tot T+ 16 34 50 

T- 7 52 59 Tot 23 86 109  Lower Upper  Value 95% CI 95% CI Se 70.9% 52.3% 89.5% Sp 60.9% 50.6% 71.2% 

PPV 32.0% 19.1% 44.9% NPV 88.1% 79.9% 96.4% 

3) Combined Doppler and Sassone score 

 Dis+ Dis- Tot T+ 17 23 40 

T- 6 63 69 Tot 23 86 109  Lower Upper  Value 95% CI 95% CI Se 74.0% 56.1% 91.9% Sp 73.7% 64.4% 83.0% 

PPV 42.5% 27.2% 57.8% NPV 91.3% 84.7% 98.0% 

Comme--Bordemaligna--2x2 tamasses --Patiengynecotimes a--No disinitial w--RI and data its--ClinicaQuality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-140

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommLerner, TimorTritsch, Federman, et al., 1994 #6360 

Geographical location: New York, NY University Hospital Dates: May 1990 – Mar 

1993 Size of population: 312 patients with 350 ovarian masses Other Retrospective analysis of US of women who had gone to surgery for adnexal mass Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes for Sasonne, no for modified criteria used here Statistical tests used: Se, Sp Blinding: Yes Definition of positive and negative on screening test: Modified Sasonne where + was ≥ 3 and +1 for shadowing present, +1 for ≥ 3 mm walls, +2 for 

solid wall structure, +3 

Age: Mean: 44.5 Range: 12-85 Menopausal status (n [%]): Pre (< 45): 228 (73%) Post (> 55): 84 (27%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Women who had surgery in time frame for whom images were available Exclusion criteria: Attempts made to not perform US in luteal phase

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) US scoring system of Sassone (cutoff ≥ 3 for T+) 

 Dis+ Dis- Tot T+ 30 72 102 

T- 1 247 248 Tot 31 319 350  Lower Upper  Value 95% CI 95% CI Se 96.8% 90.6% 100.0%Sp 77.4% 72.8% 82.0% PPV 29.4% 20.6% 38.3% NPV 99.6% 98.8% 100.0%

Comme--The ainstitutiowhich tcriteria performSassondiscuss--Denommasses --LMP tQuality ReferenVerificaTest remay ha

Sample Statistictumors BlindingDefinitio
D-141

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

for papillarities ≥ 3 mm, 

+3 for mixed or high echogenicity 

Lin, Angel, DuBeshter, et al., 1993 #4890 

Geographical location: Rochester, NY, USA Dates: Jul 1989 – Jun 

1990 Size of population: 80 women Other Case series Retrospective Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: No for US and CT (no scoring system used) Statistical tests used: P value calculated by NR Blinding: No; retrospective Definition of positive and negative on screening test: US and CT – “presence of a complex or heterogenous mass, ascites, omental tumor or other evidence of metastatic tumor in the 

Age: Median: 56 Range: 19-88 Menopausal status (n [%]): Pre (< 45): 18 (22.5%) Post (> 55): 62 (77.5) Race/ethnicity (n [%]): Caucasian 72 (90%) Black 8 (10%) Risk factors (n [%]): Family history: 11 (13.8%)Inclusion criteria: “Mass in the pelvic area” who underwent surgery in time frame Exclusion criteria: NR 

Symptomatic (n [%]): Pain - 37(46.3%) Asymptomatic – 70(87.5%) Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) US 

 Dis+ Dis- Tot T+ 15 11 26 

T- 3 11 14 Tot 18 22 40  Lower Upper  Value 95% CI 95% CI Se 83.3% 66.1% 100.0%Sp 50.0% 29.1% 70.9% PPV 57.7% 38.7% 76.7% NPV 78.6% 57.1% 100.0%

2) CT 

 Dis+ Dis- Tot T+ 25 9 34 T- 4 5 9 Tot 29 14 43  Lower Upper  Value 95% CI 95% CI Se 86.2% 73.7% 98.8% Sp 35.7% 10.6% 60.8% PPV 73.5% 58.7% 88.4% NPV 55.6% 23.1% 88.0% 

Comme--Patiengyneco--No scused --Retrosmeans malignablinding prior ra--Bordemaligna--Not alpatients each 2x--The Pdiffer sithan tha(PPV-7Quality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-142

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

pelvic area or abdomen” 

Lin, Wu, Lee, et al., 1993 #6990 

Geographical location: Taiwan University Hospital Dates: Jul 1990 – Oct 

1993 Size of population: 370 women Other Hospital referrals for adnexal masses Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: RI – yes (usually with 0.4 cutoff) Statistical tests used: Se, Sp Blinding: NR but study prospective Definition of positive and negative on screening test: RI ≤ 0.4 or 0.5 or 0.6 

Age: Mean: 40.5 Range: 11-81 Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Suspected ovarian mass on US referred to hospital for surgery Exclusion criteria: Study US in luteal phase 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): 370 (100%) Combination (n [%]): NR Additional data used for diagnosis: NR 

1) RI ≤ 0.4 

 Dis+ Dis- Tot T+ 62 8 70 

T- 28 272 300 Tot 90 280 370  Lower Upper  Value 95% CI 95% CI Se 68.9% 59.3% 78.5% Sp 97.1% 95.1% 99.1% 

PPV 88.6% 81.1% 96.0% NPV 90.7% 87.4% 94.0% 

2) RI ≤ 0.5 

 Dis+ Dis- Tot T+ 71 22 93 

T- 19 258 277 Tot 90 280 370  Lower Upper  Value 95% CI 95% CI Se 78.9% 70.5% 87.3% Sp 92.1% 88.9% 95.3% 

PPV 76.3% 67.7% 85.0% NPV 93.1% 90.2% 96.1% 

3) RI ≤ 0.6 

 Dis+ Dis- Tot T+ 82 38 120 

T- 8 242 250 Tot 90 280 370  Lower Upper  Value 95% CI 95% CI Se 91.1% 85.2% 97.0% Sp 86.4% 82.4% 90.4% 

PPV 68.3% 60.0% 76.7% NPV 96.8% 94.6% 99.0% 

Comme--Bordemaligna--“Satisonly in masses malignainclude60% noused in --Reporform as Quality ReferenVerificaTest rediscussin studySample StatisticBlindingDefinitio
D-143

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommLuxman, Bergman, Sagi, et al., 1991 #6530 

Geographical location: Tel Aviv, Israel Dates: NR 

Size of population: 102 OtherCase series Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: No Statistical tests used: Se, Sp Blinding: No Definition of positive and negative on screening test: US – unclear “simple” if lesion unilocular and lacking septa “complex” if solid area, papillae, septa, enhanced echogenicity 

Age: Mean: 62 Range: 42-90 Menopausal status (n [%]): Post (> 55): 102 (100%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: NR – presumable, presence of mass scheduled for surgery during time frame Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) US—Size > 5 cm and/or complex/solid = malignant 

 Dis+ Dis- Tot T+ 27 42 69 

T- 2 31 33 Tot 29 73 102  Lower Upper  Value 95% CI 95% CI Se 93.0% 83.7% 100.0%Sp 42.0% 30.7% 53.3% 

PPV 39.1% 27.6% 50.6% NPV 93.9% 85.8% 100.0%

2) US—size > 5 cm alone = malignant 

 Dis+ Dis- Tot T+ 24 12 36 

T- 5 61 66 Tot 29 73 102  Lower Upper  Value 95% CI 95% CI Se 82.8% 69.0% 96.5% Sp 83.6% 75.1% 92.1% PPV 66.7% 51.3% 82.1% NPV 92.4% 86.0% 98.8% 

3) US—complex or solid = malignant 

 Dis+ Dis- Tot T+ 27 33 60 T- 2 40 42 Tot 29 73 102  Lower Upper  Value 95% CI 95% CI Se 93.1% 83.9% 100.0%Sp 54.8% 43.4% 66.2% PPV 45.0% 32.4% 57.6% NPV 95.2% 88.8% 100.0%

Comme--All po42-90 --Very ugraded “compleQuality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-144

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommMa, Shen, and Lang, 2003 #1900 

Geographical location: Peking, China University Dates: Jan 1998 – June 

1999 Size of population: 140 women Other Retrospective analysis of surgical patients with CA125 and US in single academic center Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: CA-125 – yes US – unclear what scoring system used – reliability probably not established Statistical tests used: Se, Sp, PPV Blinding: NR (retrospective analysis of already collected data) Definition of positive and negative on screening test: CA-125 > (various cutoffs analyzed 30, 50, 100) 

Age: Range: 30 - NR Menopausal status (n [%]): Pre: 89 (64%) Post: 51 (36%) > 1 year of amenorrhea or if s/p hysterectomy, age > 50 years Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: “Ovarian neoplasm” patients over 30 years admitted to a single institution Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) CA-125 ≥ 30 U/ml 

 Dis+ Dis- Tot T+ 56 27 83 

T- 7 50 57 Tot 63 77 140  Lower Upper  Value 95% CI 95% CI Se 88.9% 81.1% 96.7% Sp 64.9% 54.2% 75.6% 

PPV 67.5% 57.4% 77.5% NPV 87.7% 79.2% 96.2% 

2) CA-125 ≥ 50 

 Dis+ Dis- Tot T+ 53 21 74 

T- 10 56 66 Tot 63 77 140  Lower Upper  Value 95% CI 95% CI Se 84.1% 75.1% 93.1% Sp 72.7% 62.7% 82.7% 

PPV 71.6% 61.3% 81.9% NPV 84.8% 76.2% 93.5% 

3) US score ≥ 2 

 Dis+ Dis- Tot T+ 59 13 72 

T- 4 64 68 Tot 63 77 140  Lower Upper  Value 95% CI 95% CI Se 93.7% 87.7% 99.7% Sp 83.1% 74.7% 91.5% 

PPV 81.9% 73.1% 90.8% NPV 94.1% 88.5% 99.7% 

Comme--Meno--Unclecomes --Uncleimaging --CA-12used in Quality ReferenVerificaTest re+ for CA- for US Sample StatisticBlindingDefinitio
D-145

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

US score 0 or 1 point given for: multi-focal lesion, nature of focal lesion, unilateral or bilateral lesion, ascites, metastasis Max = 5 

Maggino, Gadducci, D’Addario, et al., 1994 #4500 

Geographical location: Padua, Pisa, Bari, Brescia, and Milan, Italy Dates: Mar 1991-Mar 

1992 Size of population: 383; 48 excluded based on criteria, 45 not reported because ultrasound and CA-125 did not lead to surgery Other Multicenter series Reference standard: Surgery Reference standard applied to all test negatives?: No Test reliability established?: Not referenced or discussed (ultrasound) Statistical tests used: Se, Sp Blinding: No Definition of positive and negative on 

Age: Range: 40-91 Overall mean not reportedMenopausal status (n [%]): 100% post menopausal Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Clinical diagnosis of pelvic mass Postmenopausal at least 1 year Exclusion criteria: Premenopausal, Previous malignancy, except breast ca Previous bilateral adnexectomy Previous hysterectomy if < 55 years 

Symptomatic (n [%]): 209 (72.1%) Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) CA-125, threshold >35, EXCLUDING 45 patients not operated on because of US and CA-125 

 Dis+ Dis- Tot T+ 83 24 107 

T- 23 110 133 Tot 106 134 240  Lower Upper  Value 95% CI 95% CI Se 78.3% 70.5% 86.1% Sp 82.1% 75.6% 88.6% PPV 77.6% 69.7% 85.5% NPV 82.7% 76.3% 89.1% 

2) CA-125, threshold > 65, EXCLUDING 45 patients not operated on because of US and CA-125 

 Dis+ Dis- Tot T+ 76 10 86 T- 30 124 154 Tot 106 134 240  Lower Upper  Value 95% CI 95% CI Se 71.7% 63.1% 80.3% Sp 92.5% 88.1% 97.0% PPV 88.4% 81.6% 95.1% NPV 80.5% 74.3% 86.8% 

3) Ultrasound, equivocal or higher as positive, EXCLUDING patients not operated on because of findings 

Comme--Refereall test -2x2 tabwith adother noQuality ReferenVerificaTest reSample StatisticBlindingDefinitio + 
D-146

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

screening test: Probably benign: • < 5 cm • thin, clear wall• hypoechogenic• no septae, or no 

more than 3 thin septae

• No fluid in cul de 

sac

Equivocal: • Between 5 and 10 

cm

• Thick, clear, smooth 

wall

• Hypoechogenic 

liquid or solid homogeneous content

• > 3 thin septae• Thick, regular 

septae

• No vegetations

• No free peritoneal 

fluid

Malignant: none of the above

 Dis+ Dis- Tot T+ 105 72 177 

T- 1 62 63 Tot 106 134 240  Lower Upper  Value 95% CI 95% CI Se 99.1% 97.2% 100.0%Sp 46.3% 37.8% 54.7% PPV 59.3% 52.1% 66.6% NPV 98.4% 95.3% 100.0%

4) Ultrasound, malignant as positive, EXCLUDING patients not operated on because of findings 

 Dis+ Dis- Tot T+ 90 30 120 T- 16 104 120 Tot 106 134 240  Lower Upper  Value 95% CI 95% CI Se 84.9% 78.1% 91.7% Sp 77.6% 70.6% 84.7% PPV 75.0% 67.3% 82.7% NPV 86.7% 80.6% 92.7% 
D-147

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommMalkasian Jr., Knapp, Lavin, et al., 1988 #6810 

Geographical location: Rochester, MN; Boston, MA; Hershey, PA; Los Angeles, CA Dates: NR 

Size of population: 172; 14 excluded for total of 158 Other Multicenter, case series Reference standard: Surgery/pathologyReference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: Se/Sp Blinding: Yes Definition of positive and negative on screening test: CA-15 at various thresholds 

Age: Benign Mean: 43.5 Range: 15-88 Malignant Mean: 63.5 Range: 16-96 Menopausal status (n [%]): BenignPre (< 45): 56 (62.2%) Post (> 55): 34 (37.8%) Malignant: Pre 10 (14.7%) Post: 58 (85.3%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Palpable mass Scheduled for surgery Blood drawn within 1 week of surgery Exclusion criteria: Preop definitive diagnosis of ovarian cancer (n = 11) Blood > 1 week (n = 3) 

Symptomatic (n [%]): Clinical presentation not described Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: Stage I 23.3% II 10.0% III 61.5% IV 5.0% 

1) All patients, CA-125 > 35 as positive 

 Dis+ Dis- Tot T+ 53 18 71 

T- 15 72 87 Tot 68 90 158  Lower Upper  Value 95% CI 95% CI Se 77.9% 68.1% 87.8% Sp 80.0% 71.7% 88.3% PPV 74.6% 64.5% 84.8% NPV 82.8% 74.8% 90.7% 

2) All patients, CA-125 > 100 as threshold 

 Dis+ Dis- Tot T+ 50 4 54 T- 18 86 104 Tot 68 90 158  Lower Upper  Value 95% CI 95% CI Se 73.5% 63.0% 84.0% Sp 95.6% 91.3% 99.8% PPV 92.6% 85.6% 99.6% NPV 82.7% 75.4% 90.0% 

3) Premenopausal patients, CA-125 > 35 as threshold 

 Dis+ Dis- Tot T+ 6 15 21 T- 4 41 45 Tot 10 56 66  Lower Upper  Value 95% CI 95% CI Se 60.0% 29.6% 90.4% Sp 73.2% 61.6% 84.8% PPV 28.6% 9.2% 47.9% NPV 91.1% 82.8% 99.4% 

4) Premenopausal patients, CA-125 > 100 

Comme--Uncle--Spect--Tests surgeryhave bedecisio-- BordemalignaQuality ReferenVerificaTest reSample given) StatisticBlindingDefinitio + 
D-148

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

as threshold 

 Dis+ Dis- Tot T+ 6 3 9 

T- 4 53 57 Tot 10 56 66  Lower Upper  Value 95% CI 95% CI Se 60.0% 29.6% 90.4% Sp 94.6% 88.7% 100.0%PPV 66.7% 35.9% 97.5% NPV 93.0% 86.4% 99.6% 

5) Postmenopausal patients, CA-125 > 35 as threshold 

 Dis+ Dis- Tot T+ 47 3 50 T- 11 31 42 Tot 58 34 92  Lower Upper  Value 95% CI 95% CI Se 81.0% 70.9% 91.1% Sp 91.2% 81.6% 100.0%PPV 94.0% 87.4% 100.0%NPV 73.8% 60.5% 87.1% 

6) Postmenopausal patients, CA-125 > 100 as threshold 

 Dis+ Dis- Tot T+ 44 1 45 T- 13 33 46 Tot 57 34 91  Lower Upper  Value 95% CI 95% CI Se 77.2% 66.3% 88.1% Sp 97.1% 91.4% 100.0%PPV 97.8% 93.5% 100.0%NPV 71.7% 58.7% 84.8% 
D-149

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommMaly, Riss, and Deutinger, 1995 #6800 

Geographical location: Vienna, Austria Dates: NR 

Size of population: 102 women Other Case series Reference standard: Pathology Reference standard applied to all test negatives?: Yes Test reliability established?: Not referenced or discussed Statistical tests used: Chi-square, t-test Blinding: NR Definition of positive and negative on screening test: Diastolic notch: “short drop of flow curve at beginning of diastole” 

Age: Range: 28-75 Menopausal status (n [%]): Pre (< 45): 55 (53.9%) Post (> 55): 47 (46.1%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: NR Exclusion criteria: NR 

Symptomatic (n [%]): Clinical presentation not described Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: Premenopausal US in secretory phase 

1) Diastolic notch absent 

 Dis+ Dis- Tot T+ 37 5 42 

T- 0 39 39 Tot 37 44 81  Lower Upper  Value 95% CI 95% CI Se 100.0% 91.9% 100.0%Sp 88.6% 79.3% 98.0% PPV 88.1% 78.3% 97.9% NPV 100.0% 92.3% 100.0%

2) Demonstrable blood vessels 

 Dis+ Dis- Tot T+ 37 44 81 T- 2 19 21 Tot 39 63 102  Lower Upper  Value 95% CI 95% CI Se 94.9% 87.9% 100.0%Sp 30.2% 18.8% 41.5% PPV 45.7% 34.8% 56.5% NPV 90.5% 77.9% 100.0%

Comme--UncleconsecQuality ReferenVerificaTest reSample StatisticBlindingDefinitio - (not c
D-150

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommMancuso, De Vivo, Triolo, et al., 2004 #1610 

Geographical location: Italy University Hospital Dates: NR 

Size of population: 125 women Other Patients referred to hospital with mass who had surgery Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: CA-125 - yes US – unclear what was used Statistical tests used: Se, Sp, LR Blinding: NR (US and serum prior to surgery) Definition of positive and negative on screening test: CA-125 ≥ 35 U/ml 

US – NR what was + or negative or what scoring system used 

Age: Mean (SD): 42.2 Range: 18 - 82 Menopausal status (n [%]): Pre 76 (61%) Post 49 (39%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Patients referred to hospital with mass who had surgery Exclusion criteria: 

NR 

Symptomatic (n [%]): 68 (54.4%) symptomatic 5 (4%) had urinary or intestinal symptoms only 30 (24%) described as asymptomatic Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: 22 (17.6%) reported a menstrual disorder as main symptom 

1) US 

 Dis+ Dis- Tot T+ 14 24 38 

T- 0 87 87 Tot 14 111 125  Lower Upper  Value 95% CI 95% CI Se 100.0% 78.6% 100.0%Sp 78.6% 71.0% 86.2% 

PPV 36.8% 21.5% 52.2% NPV 100.0% 96.6% 100.0%

2) CA-125 ≥ 35 U/ml 

 Dis+ Dis- Tot T+ 14 24 38 

T- 0 87 87 Tot 14 111 125  Lower Upper  Value 95% CI 95% CI Se 100.0% 78.6% 100.0%Sp 78.6% 71.0% 86.2% 

PPV 36.8% 21.5% 52.2% NPV 100.0% 96.6% 100.0%

Comme--Menodefined --Even status cor < 50 --US sc(?SasonegativQuality ReferenVerificaTest reSample StatisticBlindingDefinitio+ for CA- for US 
D-151

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommManjunath, Pratapkumar, Sujatha, et al., 2001 #2510 

Geographical location: Manipal, India Dates: Jan 1997 – Aug 

1999 Size of population: 152 women Other Retrospective analysis of women admitted to academic hospital with pelvic mass who had surgery Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: CA-125 – yes US - ? Statistical tests used: Se, Sp, ROC curves Blinding: NR Definition of positive and negative on screening test: CA-125 (multiple cutoffs) US score 1 point given for presence of multilocular systic lesion, solid area, bilateral, ascites, intraabdominal mets. 

Age: NR Menopausal status (n [%]): Pre (< 45): 84(55.2%) Post (> 55): 64(42.1%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Patients who had surgery for pelvic masses Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) CA-125 ≥ 35 U/ml 

 Dis+ Dis- Tot T+ 77 10 87 

T- 16 45 61 Tot 93 55 148  Lower Upper  Value 95% CI 95% CI Se 83.0% 75.4% 90.6% Sp 82.0% 71.8% 92.2% 

PPV 88.5% 81.8% 95.2% NPV 73.8% 62.7% 84.8% 

2) US score ≥ 2 

 Dis+ Dis- Tot T+ 40 6 46 

T- 53 49 102 Tot 93 55 148  Lower Upper  Value 95% CI 95% CI Se 43.0% 32.9% 53.1% Sp 89.0% 80.7% 97.3% 

PPV 87.0% 77.2% 96.7% NPV 48.0% 38.3% 57.7% 

Comme--LMP tmaligna--Althoureporteby men--UncleQuality ReferenVerificaTest re125 ?/- for USample StatisticBlindingDefinitio+/- 
D-152

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommMarchetti, Zambon, Lamaina, et al., 2002 #2230 

Geographical location: Padua, Italy Dates: Sep 1996-Oct 

2001 Size of population: 176 positives/4,350 exams Screening study Reference standard: Surgery, followup Reference standard applied to all test negatives?: No Test reliability established?: Not referenced or discussed Statistical tests used: Chi-square, Se/Sp Blinding: Yes Definition of positive and negative on screening test: Criteria for referral or positive test not described 

Age: Mean: 49 Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Borderline classified as malignant Exclusion criteria: NR 

Symptomatic (n [%]): 518 (11.9%) Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: Screening frequency not described 

1) All patients with positive ultrasound, borderline classified as malignant, assuming negative ultrasound truly negative 

 Dis+ Dis- Tot T+ 2 174 176 

T- 0 4174 4174 Tot 2 4348 4350  Lower Upper  Value 95% CI 95% CI Se 100.0% 0.0% 100.0%Sp 96.0% 95.4% 96.6% PPV 1.1% 0.0% 2.7% NPV 100.0% 99.9% 100.0%

2) Patients undergoing surgery only (not clear from paper, but 29 had “ultrasound findings indicative of malignant lesions”, and 45 total underwent surgery 

 Dis+ Dis- Tot T+ 2 27 29 T- 0 16 16 Tot 2 43 45  Lower Upper  Value 95% CI 95% CI Se 100.0% 0.0% 100.0%Sp 37.2% 22.8% 51.7% PPV 6.9% 0.0% 16.1% NPV 100.0% 81.3% 100.0%

Comme--Variab--Lengtnot clea--ResulmenopaQuality ReferenVerificaTest reSample StatisticBlindingDefinitio - 
D-153

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommMarret, Sauget, Giraudeau, et al., 2004 #7680 

Geographical location: France Dates: Feb 2002 – Mar 

2003 Size of population: 99 women 101 masses Prospective series (“pilot” per authors)Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: Kappa statistics AUC Se, Sp Chi square – Fisher exact Blinding: NR Definition of positive and negative on screening test: RI < 0.53 CA-125 > 25 U/ml 

Age: Mean: 46.2 Range: 19-72 Menopausal status (n [%]): Pre (< 45): 58 (58.6%) Post (> 55): 41 (41.4%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Woman with diagnosis of adnexal mass admitted to hospital in time frame Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) RI < 0.53 

 Dis+ Dis- Tot T+ 18 13 31 

T- 5 65 70 Tot 23 78 101  Lower Upper  Value 95% CI 95% CI Se 78.0% 61.1% 94.9% Sp 83.0% 74.7% 91.3% 

PPV 58.1% 40.7% 75.4% NPV 92.9% 86.8% 98.9% 

2) CA-125 ≥ 25 

 Dis+ Dis- Tot T+ 19 12 31 

T- 4 66 70 Tot 23 78 101  Lower Upper  Value 95% CI 95% CI Se 83.0% 67.6% 98.4% Sp 85.0% 77.1% 92.9% 

PPV 61.3% 44.1% 78.4% NPV 94.3% 88.8% 99.7% 

Comme--Analywomen --Study of IV cothis is a outcomevidenc--Unablstatus --Intero0.92 --US mnot speQuality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-154

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommMatthes, Moreira de Andrade, and Bighetti, 1996 #11020 

Geographical location: Brazil Dates: Feb 1992 – Feb 

1994 Size of population: 51, however results only available for 43 Reference standard: Reference standard applied to all test negatives?: Test reliability established?: Statistical tests used: Blinding: Definition of positive and negative on screening test: 

Age: Mean: 45.75 Median: 46 Range: 15-83 Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Unclear Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) US (Kurjak morphology) 

 Dis+ Dis- Tot T+ 8 7 15 

T- 2 26 28 Tot 10 33 43  Lower Upper  Value 95% CI 95% CI Se 80.0% 55.2% 100.0%Sp 78.8% 64.8% 92.7% PPV 53.3% 28.1% 78.6% NPV 92.9% 83.3% 100.0%

Comme--8 patienot men--Kurjak classificcutpoin--LMP i--Uncleor combQuality ReferenVerificaTest reSample StatisticBlindingDefinitio+/- 
D-155

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommMcIntosh, Drescher, Karlan, et al., 2004 #6700 

Geographical location: Seattle, WA Dates: NR 

Size of population: 95/315 total including healthy controls (no mass) 52 ovarian cancer 43 benign ovarian tumors = 95 used for calculations here Other Case-control Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: ROC, LR models Blinding: NR Definition of positive and negative on screening test: SA 125 – cutoffs not selected a priori 

Age: NR Menopausal status (n [%]): Pre: 90 (29%) Post: 225 (71%) Race/ethnicity (n [%]): White: 268 (85%) Hispanic: 4 (1%%) Black: 1 (< 1%) Asian: 8 (3%) Native American: 3 (< 1%)Risk factors (n [%]): NR Inclusion criteria: Cases and controls – randomly selected from repository Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) CA-125 (cutoff not specified; sensitivity calculated corresponding to 98% specificity on ROC curve based on LR model) 

 Dis+ Dis- Tot T+ 19 1 20 

T- 33 42 75 Tot 52 43 95  Lower Upper  Value 95% CI 95% CI Se 37.2% 24.1% 50.3% Sp 98.0% 93.8% 100.0%

PPV 95.0% 85.4% 100.0%NPV 56.0% 44.8% 67.2% 

Also reported for soluble mesothelin related (SMR) marker; not reported here. 

Quality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-156

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommMedl, Kulenkampff, Stiskal, et al., 1995 #6300 

Geographical location: Vienna, Austria Dates: NR 

Size of population: 73 women Other Case series Reference standard: Surgery Reference standard applied to all test negatives?: Yes Test reliability established?: Not described or discussed Statistical tests used: Se/Sp Blinding: Not described Definition of positive and negative on screening test: Ultrasound: • Cyst with irregular 

wall 

• Wall thickness > 3 cm • Papillary wall 

structures 

• Solid components • Presence of ascites MRI: • > 4cm 

Age: NR Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: NR Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: Stage I: n=11 (29.7%) II: n=1 (2.7%) III: n=24 (64.9%) IV: n=1 (2.7%) 

1) Ultrasound 

 Dis+ Dis- Tot T+ 30 8 38 

T- 7 22 29 Tot 37 30 67  Lower Upper  Value 95% CI 95% CI Se 81.0% 68.4% 93.6% Sp 73.0% 57.1% 88.9% 

PPV 78.9% 66.0% 91.9% NPV 75.9% 60.3% 91.4% 

2) MRI 

 Dis+ Dis- Tot T+ 36 5 41 

T- 1 25 26 Tot 37 30 67  Lower Upper  Value 95% CI 95% CI Se 97.3% 92.1% 100.0%Sp 83.3% 70.0% 96.7% PPV 87.8% 77.8% 97.8% NPV 96.2% 88.8% 100.0%

Comme--Uncle--Clinica--No scif descrany of tmalignadescribQuality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-157

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

• Wall thickness > 3 

mm or nodular or other solid components 

• Entirely solid • Involvement of 

adjacent organs 

• Ascites • Lymph node > 1 cm • Peritoneal, 

mesenteric, or omental disease 

Menon, Talaat, Rosenthal, et al., 2000 #2780 

Geographical location: London, UK Dates: 1986-1989 

Size of population: 22,000 in prevalence screen, 10,958 randomized to 3 annual incidence screens. Results based on 741women Screening study Reference standard: Surgery, registry diagnosis of cancer, followup questionnaire Reference standard applied to all test negatives?: Yes Test reliability established?: 

Not referenced or discussedStatistical tests used: 

Age: NR Menopausal status (n [%]): 100% postmenopausal, > 45 Race/ethnicity (n [%]): NR Risk factors (n [%]): All with elevated CA-125 Inclusion criteria: NR Exclusion criteria: 

NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: All with CA-125 > 30 75.3% of scans transabdominal, 8.4% transvaginal, 16.2% both 

All results given using number of scans as denominator (n = 1219), disease defined as incident cancer within 1 year of scan 1) Abnormal volume as threshold 

 Dis+ Dis- Tot T+ 17 63 80 

T- 2 945 947 Tot 19 1008 1027  Lower Upper  Value 95% CI 95% CI Se 89.5% 75.7% 100.0%Sp 93.8% 92.3% 95.2% PPV 21.3% 12.3% 30.2% NPV 99.8% 99.5% 100.0%

2) Abnormal morphology as threshold 

 Dis+ Dis- Tot T+ 19 61 80 T- 0 947 947 Tot 19 1008 1027  Lower Upper  Value 95% CI 95% CI Se 100.0% 84.2% 100.0%Sp 93.9% 92.5% 95.4% PPV 23.8% 14.4% 33.1% NPV 100.0% 99.7% 100.0%

Comme--AuthodifferenunderpoQuality ReferenVerificaTest reSample small nStatisticBlindingDefinitio + 
D-158

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

Se/Sp Blinding: Yes Definition of positive and negative on screening test: If CA-125 > 30 U/ml, ultrasound If ultrasound normal: < 8.8 ml volume, uniform hypoechogenicity, smooth outlines, or not visualized but no abnormality repeated CA-125 q 3 months x 1 year, then annual screening: Equivocal: Ovarian volume < 8.8 ml with abnormal morphology: repeat scan q 6 weeks until either normal or abnormal scan Abnormal: Ovarian volume > 8.8 ml, referred to gynecologist, with management at their discretion 

3) Complex morphology as threshold 

 Dis+ Dis- Tot T+ 16 27 43 

T- 3 981 984 Tot 19 1008 1027  Lower Upper  Value 95% CI 95% CI Se 84.2% 67.8% 100.0%Sp 97.3% 96.3% 98.3% PPV 37.2% 22.8% 51.7% NPV 99.7% 99.4% 100.0%
D-159

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommMerce, Caballero, Barco, et al., 1998 #3510 

Geographical location: Spain Dates: 1990 - 1995 

Size of population: 213 129 had surgery Other Patients with masses ?referred to hospital Reference standard: Histopathology for those in surgery, repeat US for the others Reference standard applied to all test negatives?: No Test reliability established?: Unclear for US score Yes for RI Statistical tests used: ROC curves Blinding: NR but US prior to surgery Definition of positive and negative on screening test: RI ≤ 0.5 For US sonographic index score ≥ 6 which was volume + morphology score 

Age: Mean: 41 Range: 15 - 87 Menopausal status 

(n [%]): 

NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Premenopausal women with ovarian mass >28mm in diameter, or >10mm for menopausal women. Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) US score ≥ 6 

 Dis+ Dis- Tot T+ 21 34 55 

T- 1 73 74 Tot 22 107 129  Lower Upper  Value 95% CI 95% CI Se 95.5% 86.8% 100.0%Sp 68.2% 59.4% 77.0% PPV 38.2% 25.3% 51.0% NPV 98.6% 96.0% 100.0%

2) RI ≤ 0.5 

 Dis+ Dis- Tot T+ 18 36 54 T- 4 71 75 Tot 22 107 129  Lower Upper  Value 95% CI 95% CI Se 80.0% 63.3% 96.7% Sp 66.7% 57.8% 75.6% 

PPV 33.3% 20.8% 45.9% NPV 94.7% 89.6% 99.8% 

Comme--Time diagnoswas 2 w--US scdifferenhow relnot des--2x2 tahad surQuality Referenbased osurgery Verificain 213-Test reSample StatisticBlindingDefinitio
D-160

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommMorgante, la Marca, Ditto, et al., 1999 #2900 

Geographical location: Siena, Italy Dates: Jan 1995 – Dec 

1997 Size of population: 124 Other Case series Consecutive admissions for surgery Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: Se, Sp, ROC Chi-square Mann-Whitney U test Blinding: NR - prospective Definition of positive and negative on screening test: CA-125 – range used US score: Presence of multilocular cystic lesions (1), solid areas (1), bilateral lesions (1), ascites (1), intraabdominal mets (1) 

Age: NR: Menopausal status (n [%]): Pre (< 45): 69 (55.6%) Post (> 55): 55 (44.3%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Age >30 Mass scheduled for surgery in time frame Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) US score of 2 

 Dis+ Dis- Tot T+ 22 12 34 

T- 9 81 90 Tot 31 93 124  Lower Upper  Value 95% CI 95% CI Se 71.0% 55.0% 87.0% Sp 87.0% 80.2% 93.8% 

PPV 64.7% 48.6% 80.8% NPV 90.0% 83.8% 96.2% 

2) CA-125 ≥ 25 U/ml 

 Dis+ Dis- Tot T+ 24 15 39 

T- 7 78 85 Tot 31 93 124  Lower Upper  Value 95% CI 95% CI Se 78.0% 63.4% 92.6% Sp 84.0% 76.5% 91.5% 

PPV 61.5% 46.3% 76.8% NPV 91.8% 85.9% 97.6% 

3) CA-125 ≥ 50 U/ml 

 Dis+ Dis- Tot T+ 23 5 28 

T- 8 88 96 Tot 31 93 124  Lower Upper  Value 95% CI 95% CI Se 74.0% 58.6% 89.4% Sp 95.0% 90.6% 99.4% 

PPV 82.1% 68.0% 96.3% NPV 91.7% 86.1% 97.2% 

Comme--What score n--BordemalignaQuality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-161

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommO’Connell, Ryan, Murphy, et al., 1987 #6690 

Geographical location: Hamilton, Ontario Dates: Nov 1984-May 

1986 Size of population: 56 women Other Case series Reference standard: Surgery/pathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: Se/Sp/ROC Blinding: Yes Definition of positive and negative on screening test: Varied 

Age: Mean (SD): 55 Range: 13-81 Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: NR Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: “High clinical suspicion of ovarian cancer” CA-125 drawn within 3 days of surgery 

1) CA-125 threshold >35 U/ml, ovarian cancer vs. any other diagnosis (including other malignancy) 

 Dis+ Dis- Tot T+ 26 17 43 

T- 0 13 13 Tot 26 30 56  Lower Upper  Value 95% CI 95% CI Se 100.0% 88.5% 100.0%Sp 43.3% 25.6% 61.1% PPV 60.5% 45.9% 75.1% NPV 100.0% 76.9% 100.0%

2) CA-125 threshold > 60 U/ml, ovarian cancer vs. any other diagnosis (including other malignancy) 

 Dis+ Dis- Tot T+ 24 12 36 T- 2 18 20 Tot 26 30 56  Lower Upper  Value 95% CI 95% CI Se 92.0% 81.6% 100.0%Sp 60.0% 42.5% 77.5% 

PPV 66.7% 51.3% 82.1% NPV 90.0% 76.9% 100.0%

3) CA-125 threshold > 35 U/ml, any malignancy vs. benign 

 Dis+ Dis- Tot T+ 36 7 43 

T- 2 11 13 Tot 38 18 56  Lower Upper  Value 95% CI 95% CI Se 95.0% 88.1% 100.0%Sp 61.0% 38.5% 83.5% 

Comme--Clinica--Very h--BordemalignaQuality ReferenVerificaTest reSample StatisticBlindingDefinitio + 
D-162

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

PPV 83.7% 72.7% 94.8% NPV 84.6% 65.0% 100.0%

4) CA-125 threshold > 60 U/ml, any malignancy vs. benign 

 Dis+ Dis- Tot T+ 33 3 36 T- 5 15 20 Tot 38 18 56  Lower Upper  Value 95% CI 95% CI Se 87.0% 76.3% 97.7% Sp 83.0% 65.6% 100.0%

PPV 91.7% 82.6% 100.0%NPV 75.0% 56.0% 94.0% 
D-163

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommOnsrud, Shabana, and Austgulen, 1996 #3950 

Geographical location: Trondheim, Norway Dates: NR 

Size of population: 72 women Other Case series Reference standard: Surgery/pathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: Wilcoxon rank sum, Se/Sp Blinding: Yes Definition of positive and negative on screening test: Varied 

Age: Range: 19-80 years Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: NR Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: Stage I: 20/45 (44.4%) Stage II: 1/45 (2.2%) Stage III: 21/45 (46.7%) Stage IV: 1/45 (2.2%) 

1) CA-125 > 20 U/ml 

 Dis+ Dis- Tot T+ 37 4 41 

T- 8 23 31 Tot 45 27 72  Lower Upper  Value 95% CI 95% CI Se 82.0% 70.8% 93.2% Sp 85.0% 71.5% 98.5% 

PPV 90.2% 81.2% 99.3% NPV 74.2% 58.8% 89.6% 

2) TNF p 55 > 2.0 ng/ml 

 Dis+ Dis- Tot T+ 26 3 29 

T- 19 24 43 Tot 45 27 72  Lower Upper  Value 95% CI 95% CI Se 58.0% 43.6% 72.4% Sp 89.0% 77.2% 100.0%

PPV 89.7% 78.6% 100.0%NPV 55.8% 41.0% 70.7% 

3) TNF p 75 > 4.3 ng/ml 

 Dis+ Dis- Tot T+ 7 1 8 

T- 38 26 64 Tot 45 27 72  Lower Upper  Value 95% CI 95% CI Se 16.0% 5.3% 26.7% Sp 96.0% 88.6% 100.0%

PPV 87.5% 64.6% 100.0%NPV 40.6% 28.6% 52.7% 

Comme--Clinica--Spect--Patiendescrib-- CA-1mean +women Quality ReferenVerificaTest reSample StatisticBlindingDefinitio + 
D-164

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommPadungsutt, Thirapagawong, Senapad, et al., 2000 #520 

Geographical location: Bangkok, Thailand Dates: May 1996-Mar 

1997 Size of population: 92 women Other Case series Reference standard: Surgery Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: Blinding: Definition of positive and negative on screening test: 

Age: Mean (SD): 38.8 (2.8) Range: 10-69 Menopausal status (n [%]): Pre (< 45): 64 (69.6%) Post (> 55): 28 (30.4%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: NR Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: Stage I: 17/40 (42.5%) Stage II: 3/40 (7.5%) Stage III: 20/40 (50%) 

1) Tissue polypeptide specific antigen > 80 U/L 

 Dis+ Dis- Tot T+ 36 15 51 

T- 4 37 41 Tot 40 52 92  Lower Upper  Value 95% CI 95% CI Se 90.0% 80.7% 99.3% Sp 71.2% 58.8% 83.5% PPV 70.6% 58.1% 83.1% NPV 90.2% 81.2% 99.3% 

Comme--Clinica--Not ststatus --Patiendescrib--Bordemaligna--Not a Quality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-165

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommPatsner and Mann, 1988 #5360 

Geographical location: Stony Brook, NY Dates: Jul 1985-Jul 

1987 Size of population: 250 women Other Consecutive case series Reference standard: Surgery/pathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: Se/Sp Blinding: Yes Definition of positive and negative on screening test: CA-125 > 35 

Age: NR Menopausal status (n [%]): Pre (< 45): 125 (50%) Post (> 55): 125 (50%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: NR Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: Invasive ovarian cancer Stage I: 14/80 (17.5%) Stage II: 3/80 (3.8%) Stage III: 50/80 (62.5%) Stage IV: 13/80 (16.3%) 

1) CA-125 > 35 U/ml, All patients 

 Dis+ Dis- Tot T+ 92 25 117 

T- 36 97 133 Tot 128 122 250  Lower Upper  Value 95% CI 95% CI Se 71.9% 64.1% 79.7% Sp 79.5% 72.3% 86.7% PPV 78.6% 71.2% 86.1% NPV 72.9% 65.4% 80.5% 

2) CA-125 > 35 U/ml, Premenopausal 

 Dis+ Dis- Tot T+ 33 16 49 T- 18 58 76 Tot 51 74 125  Lower Upper  Value 95% CI 95% CI Se 65.0% 51.9% 78.1% Sp 78.0% 68.6% 87.4% 

PPV 67.3% 54.2% 80.5% NPV 76.3% 66.8% 85.9% 

3) CA-125 > 35 U/ml, Postmenopausal 

 Dis+ Dis- Tot T+ 59 9 68 

T- 18 39 57 Tot 77 48 125  Lower Upper  Value 95% CI 95% CI Se 77.0% 67.6% 86.4% Sp 81.0% 69.9% 92.1% 

PPV 86.8% 78.7% 94.8% NPV 68.4% 56.4% 80.5% 

Comme--Clinica--BordemalignaQuality ReferenVerificaTest reSample StatisticBlindingDefinitio + 
D-166

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommPrompeler, Madjar, and Sauerbrei, 1996 #3960 

Geographical location: Freiburg, Germany Dates: Jul 1992-Jul 

1994 Size of population: 212 consecutive cases Other Case series Reference standard: Surgery Reference standard applied to all test negatives?: Yes Test reliability established?: Discussed Statistical tests used: Spearman’s, MannWhitney, See/Sp Blinding: No Definition of positive and negative on screening test: 20 different measures of ovarian vascularity, flow studied. 4 best criteria were • Minimum resistive 

index (difference of peak systolic and maximum end diastolic, divided by peak systolic flow velocity; cutpoint 0.5 

Age: NR Menopausal status (n [%]): Pre (< 45): 81 (38.2%) Post (> 55): 131 (61.8%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: NR Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: US timed to surgery date – therefore not all premenopausal US done in proliferative phase 

Malignant disease includes borderline (n = 9) 1) Total number of arteries > 4, all patients 

 Dis+ Dis- Tot T+ 56 34 90 

T- 12 110 122 Tot 68 144 212  Lower Upper  Value 95% CI 95% CI Se 82.4% 73.3% 91.5% Sp 76.4% 69.5% 83.3% 

PPV 62.2% 52.2% 72.2% NPV 90.2% 84.9% 95.4% 

2) Total number of arteries > 4, postmenopausal 

 Dis+ Dis- Tot T+ 45 14 59 

T- 10 62 72 Tot 55 76 131  Lower Upper  Value 95% CI 95% CI Se 81.8% 71.6% 92.0% Sp 81.6% 72.9% 90.3% 

PPV 76.3% 65.4% 87.1% NPV 86.1% 78.1% 94.1% 

3) Total number of arteries > 4, premenopausal 

 Dis+ Dis- Tot T+ 11 20 31 

T- 2 48 50 Tot 13 68 81  Lower Upper  Value 95% CI 95% CI Se 84.6% 65.0% 100.0%Sp 70.6% 59.8% 81.4% 

Comme--Clinica--LMP tmalignaQuality ReferenVerificaTest reSample power) StatisticBlindingDefinitio
D-167

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

• Total number of 

tumor arteries in color mode; cutpoint 4 

• Maximum systolic 

flow velocity; cutpoint 30 cm/sec 

• Sum of all systolic 

flow velocities; cutpoint 75 cm/sec 

PPV 35.5% 18.6% 52.3% NPV 96.0% 90.6% 100.0%

4) Min resistive index > 0.5, all patients 

 Dis+ Dis- Tot T+ 56 59 115 

T- 12 85 97 Tot 68 144 212  Lower Upper  Value 95% CI 95% CI Se 82.1% 73.0% 91.2% Sp 59.2% 51.2% 67.2% 

PPV 48.7% 39.6% 57.8% NPV 87.6% 81.1% 94.2% 

5) Min resistive index, postmenopausal 

 Dis+ Dis- Tot T+ 45 23 68 

T- 10 53 63 Tot 55 76 131  Lower Upper  Value 95% CI 95% CI Se 81.5% 71.2% 91.8% Sp 69.2% 58.8% 79.6% 

PPV 66.2% 54.9% 77.4% NPV 84.1% 75.1% 93.2% 

6) Min resistive index, premenopausal 

 Dis+ Dis- Tot T+ 11 36 47 

T- 2 32 34 Tot 13 68 81  Lower Upper  Value 95% CI 95% CI Se 84.6% 65.0% 100.0%Sp 47.1% 35.2% 58.9% PPV 23.4% 11.3% 35.5% NPV 94.1% 86.2% 100.0%
D-168

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

7) Maximum systolic velocity, all patients 

 Dis+ Dis- Tot T+ 54 33 87 

T- 14 111 125 Tot 68 144 212  Lower Upper  Value 95% CI 95% CI Se 79.1% 69.4% 88.8% Sp 76.8% 69.9% 83.7% 

PPV 62.1% 51.9% 72.3% NPV 88.8% 83.3% 94.3% 

8) Max systolic velocity, postmenopausal 

 Dis+ Dis- Tot T+ 42 9 51 

T- 13 67 80 Tot 55 76 131  Lower Upper  Value 95% CI 95% CI Se 75.9% 64.6% 87.2% Sp 87.7% 80.3% 95.1% 

PPV 82.4% 71.9% 92.8% NPV 83.8% 75.7% 91.8% 

9) Max systolic velocity, premenopausal 

 Dis+ Dis- Tot T+ 21 24 45 

T- 1 44 45 Tot 22 68 90  Lower Upper  Value 95% CI 95% CI Se 95.5% 86.8% 100.0%Sp 64.7% 53.3% 76.1% PPV 46.7% 32.1% 61.2% NPV 97.8% 93.5% 100.0%

10) Sum of systolic velocities, all patients 
D-169

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

 Dis+ Dis- Tot T+ 61 38 99 T- 7 106 113 Tot 68 144 212  Lower Upper  Value 95% CI 95% CI Se 89.6% 82.3% 96.9% Sp 73.6% 66.4% 80.8% 

PPV 61.6% 52.0% 71.2% NPV 93.8% 89.4% 98.2% 

11) Sum of systolic velocities, postmenopausal 

 Dis+ Dis- Tot T+ 50 12 62 

T- 5 64 69 Tot 55 76 131  Lower Upper  Value 95% CI 95% CI Se 90.7% 83.0% 98.4% Sp 84.6% 76.5% 92.7% 

PPV 80.6% 70.8% 90.5% NPV 92.8% 86.6% 98.9% 
D-170

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommPyrgiotis, Salamalekis, Loghis, et al., 1993 #4790 

Geographical location: Athens, Greece Dates: NR 

Size of population: 126 women Other Case series Reference standard: Surgery/pathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: Se/Sp Blinding: Yes Definition of positive and negative on screening test: CA-125 > 35 U/ml 

Age: NR Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: NR Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) All pelvic masses Borderline included as malignant (n = 4) CA-125 > 35 U/ml 

 Dis+ Dis- Tot T+ 48 7 55 

T- 14 57 71 Tot 62 64 126  Lower Upper  Value 95% CI 95% CI Se 77.4% 67.0% 87.8% Sp 89.1% 81.4% 96.7% PPV 87.3% 78.5% 96.1% NPV 80.3% 71.0% 89.5% 

2) Ovarian masses only (excluding fibroids etc) 

 Dis+ Dis- Tot T+ 46 3 49 T- 8 26 34 Tot 54 29 83  Lower Upper  Value 95% CI 95% CI Se 85.2% 75.7% 94.7% Sp 89.7% 78.6% 100.0%PPV 93.9% 87.2% 100.0%NPV 76.5% 62.2% 90.7% 

Comme--Clinica--Drawn Quality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-171

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommRehn, Lohmann, and Rempen, 1996 #3910 

Geographical location: Wurzburg, Germany Dates: Mar 1992 – Dec 

1994 Size of population: 310 Case series

Reference standard: Histopathology Reference standard applied to all test negatives?: Yes for 300 women 10 premenopausal women were “followed up to resolution” Test reliability established?: Yes Statistical tests used: Chi square U test Wilcoxon test Regression analysis Blinding: NR Definition of positive and negative on screening test: US morphology – Sassone’s criteria score ≥ 9 as well as presence of “inhomogeneous echogenicity, irregular wall, or solid portion” considered suggestive of 

Age: Mean: 43.5 Range: 17-88 Menopausal status (n [%]): Pre (< 45): 227 (73%) Post (> 55): 83(27%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Unclear – presumably women with masses in hospital during time frame who had US Exclusion criteria: Uterine malignancy 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): 310(100%) Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Sassone’s score ≥ 9 

 Dis+ Dis- Tot T+ 43 70 113 

T- 8 189 197 Tot 51 259 310  Lower Upper  Value 95% CI 95% CI Se 84.0% 73.9% 94.1% Sp 73.0% 67.6% 78.4% 

PPV 38.1% 29.1% 47.0% NPV 95.9% 93.2% 98.7% 

2) US morphology descriptive (group 4) 

 Dis+ Dis- Tot T+ 46 91 137 

T- 5 168 173 Tot 51 259 310  Lower Upper  Value 95% CI 95% CI Se 90.0% 81.8% 98.2% Sp 65.0% 59.2% 70.8% 

PPV 33.6% 25.7% 41.5% NPV 97.1% 94.6% 99.6% 

3) PI ≤ 1.0 

 Dis+ Dis- Tot T+ 34 122 156 

T- 17 137 154 Tot 51 259 310  Lower Upper  Value 95% CI 95% CI Se 67.0% 54.1% 79.9% Sp 53.0% 46.9% 59.1% 

PPV 21.8% 15.3% 28.3% NPV 89.0% 84.0% 93.9% 

Comme--Documbenign --Uncleretrospe--LMP tmaligna--Overlamaligna--Regrenegativsize for total, bubenign --TVUS Quality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-172

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

malignancy PI ≤ 1.0 

Reles, Wein, and Lichtenegger, 1997 #6090 

Geographical location: Berlin, Germany Dates: Mar 1992-Aug 

1994 Size of population: 98 women Other Case series Reference standard: Surgery/pathology Reference standard applied to all test negatives?: Yes Test reliability established?: Not referenced or discussed Statistical tests used: Chi-square, MannWhitney, Se/Sp Blinding: NR Definition of positive and negative on screening test: Morphology: Malignant if • Complex cystic 

pattern with irregularly thick septae 

• Cystic or polycystic 

Age: NR Menopausal status (n [%]): Pre (< 45):33 (36.3%) Post (> 55): 52 (57.1%) Unknown: 5 (5.55%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: NR Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

Cancers of non-ovarian origin (n = 7) not included 1) TVUS, all patients 

 Dis+ Dis- Tot T+ 20 11 31 

T- 2 58 60 Tot 22 69 91  Lower Upper  Value 95% CI 95% CI Se 90.9% 78.9% 100.0%Sp 84.1% 75.4% 92.7% PPV 64.5% 47.7% 81.4% NPV 96.7% 92.1% 100.0%

2) TVUS, premenopausal (n = 33) 

 Dis+ Dis- Tot T+ 5 6 11 T- 0 22 22 Tot 5 28 33  Lower Upper  Value 95% CI 95% CI Se 100.0% 40.0% 100.0%Sp 78.6% 63.4% 93.8% PPV 45.5% 16.0% 74.9% NPV 100.0% 86.4% 100.0%

3) TVUS, postmenopausal (n = 52) 

 Dis+ Dis- Tot T+ 13 4 17 T- 2 33 35 Tot 15 37 52 

Comme--Clinica-- 2x2 tamenopaapproxiconsistefor somNPV Quality ReferenVerificaTest reSample StatisticBlindingDefinitio + 
D-173

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

pattern with papillary or indented mural part 

• Polycystic pattern with 

irregularly thick septae and solid part < 50% 

• Solid pattern 

(>50%) with irregular cystic part 

• Completely solid 

homogeneous or inhomogeneous patter 

(modified morphology classification from Vera 1986 and Kawai 1992) Color Doppler Pulsatility index ≤ 1.1 

Resistive index 0.7 Lowest measured PI and RI used 

 Lower Upper  Value 95% CI 95% CI Se 86.7% 69.5% 100.0%

Sp 89.2% 79.2% 99.2% PPV 76.5% 56.3% 96.6% NPV 94.3% 86.6% 100.0%

4) Color Doppler pulsatility index < 1.1 

 Dis+ Dis- Tot T+ 18 12 30 

T- 2 34 36 Tot 20 46 66  Lower Upper  Value 95% CI 95% CI Se 90.0% 76.9% 100.0%Sp 74.0% 61.3% 86.7% 

PPV 60.1% 42.5% 77.6% NPV 94.5% 87.0% 100.0%

5) Color Doppler pulsatility index < 1.1, 

premenopausal (n = 24) 

 Dis+ Dis- Tot T+ 4 6 10 

T- 1 13 14 Tot 5 19 24  Lower Upper  Value 95% CI 95% CI Se 80.0% 44.9% 100.0%Sp 68.4% 47.5% 89.3% PPV 40.0% 9.6% 70.4% NPV 92.9% 79.4% 100.0%

6) Color Doppler pulsatility index < 1.1, 

postmenopausal (n = 37) 

 Dis+ Dis- Tot T+ 13 4 17 

T- 1 19 20 Tot 14 23 37 
D-174

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

 Lower Upper  Value 95% CI 95% CI Se 92.9% 79.4% 100.0%

Sp 82.6% 67.1% 98.1% PPV 76.5% 56.3% 96.6% NPV 95.0% 85.4% 100.0%

Reuter, Steffens, Schuppler, et al., 1998 #10990 

Geographical location: Germany Dates: Jan 1994 – Aug 1995 Size of population: 65 Case series (retrospective)Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: Chi square Blinding: NR Definition of positive and negative on screening test: Used criteria from reference [16] Malignancy assumed if 

Age: Mean: 48.8 Range: 18-84 Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Patients with suspected adnexal tumors in time frame Exclusion criteria: 

NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) MRI 

 Dis+ Dis- Tot T+ 12 12 24 

T- 0 41 41 Tot 12 53 65  Lower Upper  Value 95% CI 95% CI Se 100.0% 75.0% 100.0%Sp 78.2% 67.1% 89.3% 

PPV 50.0% 30.0% 70.0% NPV 100.0% 92.7% 100.0%

2) TVUS 

 Dis+ Dis- Tot T+ 12 18 30 

T- 0 35 35 Tot 12 53 65  Lower Upper  Value 95% CI 95% CI Se 100.0% 75.0% 100.0%Sp 65.5% 52.7% 78.3% 

PPV 40.0% 22.5% 57.5% NPV 100.0% 91.4% 100.0%

Comme--For Mdifferenimaging --Diagnconfere2 radiolto each --No mepatholo--Used (citation --Borde-TVUS Quality ReferenVerificaTest reSample StatisticBlindingDefinitio+/- 
D-175

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

one or more of the following was present: solid growth or solid component wall with or without necrosis; cystic lesion with thickness of walls or septa more than 3 mm; nodular or papillary projections; excessive multilocularity; infiltration in neighboring organs or pelvic wall; tumor manifestation in the peritoneum, mesentery, omentum; lymphadenopathy. Benign was none of the above present 

Roman, Muderspach, Burnett, et al., 1998 #3410 

Geographical location: Los Angeles, CA Dates: Jul 1992-Mar 

1994 Size of population: 226 women Other Case series Reference standard: Surgery/pathology Reference standard applied to all test negatives?: Yes Test reliability established?: 

Yes Statistical tests used: Fisher’s exact test, Se/Sp 

Age: Mean: 39 Range: 13-80 Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Isolated pelvic mass with surgery planned Exclusion criteria: 

Emergency surgery Evidence of metastases Past history of cancer 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) CEA > 3 ng/ml, borderline classified as malignant 

 Dis+ Dis- Tot T+ 7 13 20 

T- 25 181 206 Tot 32 194 226  Lower Upper  Value 95% CI 95% CI Se 21.9% 7.6% 36.2% Sp 93.3% 89.8% 96.8% PPV 35.0% 14.1% 55.9% NPV 87.9% 83.4% 92.3% 

2) CEA > 3 ng/ml, borderline classified as benign 

 Dis+ Dis- Tot T+ 5 15 20 T- 17 189 206 Tot 22 204 226  Lower Upper 

Value 95% CI 95% CI

Comme--Clinica--Not stmenopa--BordemalignaQuality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-176

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

Blinding: Yes Definition of positive and negative on screening test: CEA: > 3.0 ng/ml in nonsmokers, > 5.0 ng/ml in smokers 

Se 22.7% 5.2% 40.2% 

Sp 92.6% 89.1% 96.2% PPV 25.0% 6.0% 44.0% NPV 91.7% 88.0% 95.5% 

Roman, Muderspach, Stein, et al., 1997 #6160 

Geographical location: Los Angeles, CA Dates: Jul 1992-Mar 

1994 Size of population: 226 Other Non-consecutive case series Reference standard: Surgery/pathology Reference standard applied to all test negatives?: Yes Test reliability established?: Statistical tests used: Chi-square, logistic regression, Se/Sp Blinding: NR Definition of positive and negative on 

Age: NR Menopausal status (n [%]): Pre (< 45): 181 (80.1%) Post (> 55): 45 (19.9%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Isolated pelvic mass with surgery planned Exclusion criteria: Emergency surgery Evidence of metastases Past history of cancer 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Borderline classified as malignant CA-125 > 35 U/ml 

 Dis+ Dis- Tot T+ 29 54 83 

T- 14 129 143 Tot 43 183 226  Lower Upper  Value 95% CI 95% CI Se 67.4% 53.4% 81.4% Sp 70.5% 63.9% 77.1% PPV 34.9% 24.7% 45.2% NPV 90.2% 85.3% 95.1% 

2) Any positive tumor marker 

 Dis+ Dis- Tot T+ 31 55 86 T- 12 128 140 Tot 43 183 226  Lower Upper  Value 95% CI 95% CI Se 72.1% 58.7% 85.5% Sp 70.0% 63.4% 76.6% 

PPV 36.1% 25.9% 46.2% NPV 91.4% 86.8% 96.1% 

3) Any positive tumor marker, postmenopausal 

Comme--Clinica--US auused, hmakes not numQuality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-177

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

screening test: CA-125: >35 U/mL HCG: > 15 AFP: > 10 ng/ml LDH: > 350 U/L Gray scale ultrasound: Cystic with one large (> 2 cm) or multiple nodules or cystic/solid; completely solid masses not appearing to arise from the uterus in postmenopausal women Simplified scoring system used (not described in scoring fashion) Doppler (only if gray scale suspicious) PI < 1.0 or RI < 0.4 

 Dis+ Dis- Tot T+ 11 6 17 

T- 5 23 28 Tot 16 29 45  Lower Upper  Value 95% CI 95% CI Se 68.8% 46.1% 91.5% Sp 79.3% 64.6% 94.0% 

PPV 64.7% 42.0% 87.4% NPV 82.1% 68.0% 96.3% 

4) Ultrasound—all patients 

 Dis+ Dis- Tot T+ 38 24 62 

T- 5 159 164 Tot 43 183 226  Lower Upper  Value 95% CI 95% CI Se 88.4% 78.8% 98.0% Sp 86.9% 82.0% 91.8% 

PPV 61.3% 49.2% 73.4% NPV 97.0% 94.3% 99.6% 

5) Ultrasound: Premenopausal 

 Dis+ Dis- Tot T+ 25 13 38 

T- 2 141 143 Tot 27 154 181  Lower Upper  Value 95% CI 95% CI Se 92.6% 82.7% 100.0%Sp 91.6% 87.2% 96.0% 

PPV 65.9% 50.8% 81.0% NPV 98.6% 96.7% 100.0%

6) Ultrasound: Postmenopausal 

 Dis+ Dis- Tot T+ 13 11 24 

T- 3 18 21
D-178

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

Tot 16 29 45 

 Lower Upper  Value 95% CI 95% CI Se 81.3% 62.2% 100.0%Sp 62.1% 44.4% 79.8% 

PPV 54.2% 34.3% 74.1% NPV 85.8% 70.8% 100.0%

Salem, White, and Lai, 1994 #4430 

Geographical location: Toronto, Canada Dates: Sep 1992 – Jan 

1994 Size of population: 99 patients 102 masses from among 377 women with adnexal mass at sonography Other Referral series Reference standard: Histopathology Reference standard applied to all test negatives?: No Test reliability established?: US – probably Sassone PI yes Statistical tests used: Se, Spec Blinding: Yes 

Age: Range: 15-58 Menopausal status (n [%]): Pre (< 45): 57 (57.6%) Peri (45-54): 23 (23.2%) Post (> 55): 19 (19.2%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Women with diagnosis of mass referred for surgery Exclusion criteria: Studies done not in first 10 days after menstruation in premenopausal women (to avoid luteal phase) PI that couldn’t be measured due to no flow (present in 7 masses) 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): 100% had adnexal mass detected at sonography Combination (n [%]): NR Additional data used for diagnosis: NR 

1) PI < 1 

 Dis+ Dis- Tot T+ 10 17 27 

T- 3 65 68 Tot 13 82 95  Lower Upper  Value 95% CI 95% CI Se 76.9% 54.0% 99.8% Sp 79.3% 70.5% 88.0% PPV 37.0% 18.8% 55.3% NPV 95.6% 90.7% 100.0%

2) PI < 1, peri- and postmenopausal patients 

 Dis+ Dis- Tot T+ 8 9 17 T- 3 22 25 Tot 11 31 42  Lower Upper  Value 95% CI 95% CI Se 72.7% 46.4% 99.0% Sp 71.0% 55.0% 86.9% PPV 47.1% 23.3% 70.8% NPV 88.0% 75.3% 100.0%

3) PI < 1, premenopausal patients 

 Dis+ Dis- Tot T+ 2 8 10 T- 0 43 43

Comme--Analyindividu--No flolesions--ScorinSasonndescrib--But unto consQuality ReferenVerificahad hisadnexaTest reSample StatisticBlindingDefinitiofor PI 
D-179

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

Definition of positive and negative on screening test: Pulsatility index (PI) = (PSV-EDV)/mean velocity. Considered positive if < 1. 

Tot 2 51 53 

 Lower Upper  Value 95% CI 95% CI Se 100.0% 0.0% 100.0%Sp 84.3% 74.3% 94.3% PPV 20.0% 0.0% 44.8% NPV 100.0% 93.0% 100.0%

4) PI < 1, age > 45 years 

 Dis+ Dis- Tot T+ 8 3 11 T- 9 22 31 Tot 17 25 42  Lower Upper  Value 95% CI 95% CI Se 47.1% 23.3% 70.8% Sp 88.0% 75.3% 100.0%PPV 72.7% 46.4% 99.0% NPV 71.0% 55.0% 86.9% 
D-180

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommSassone, TimorTritsch, Artner, et al., 1991 #6780 

Geographical location: New York, NY Dates: Jun 1987 – Dec 

1989 Size of population: 143 women Retrospective case series Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: No Statistical tests used: Se, Sp Correlation coefficient for US and pathology Blinding: Yes Definition of positive and negative on screening test: Sassone ≥ 9 

Age: Mean: 41.6 Median: 41 Range: 20-85 Menopausal status (n [%]): Pre (< 45): 116(80.4%) Post (> 55): 24(16.8%) 3 unknown secondary to hysterectomy (2.1%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: All laparotomy performed for gynecologic indications in hospital in time frame Exclusion criteria: 

Pregnancy Previous BSO Previous treated carcinoma 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Sassone ≥ 9 

 Dis+ Dis- Tot T+ 13 22 35 

T- 0 108 108 Tot 13 130 143  Lower Upper  Value 95% CI 95% CI Se 100.0% 76.9% 100.0%Sp 83.0% 76.5% 89.5% 

PPV 37.1% 21.1% 53.2% NPV 100.0% 97.2% 100.0%

Comme--This is describsystem with ph--Bordebenign --No mepatients --TVUS Quality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-181

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommSawicki, Spiewankiewicz, Cendrowski, et al., 2001 #2450 

Geographical location: Warsaw, Poland Dates: NR 

Size of population: 329 women Other Case series Reference standard: Surgery/pathology Reference standard applied to all test negatives?: Yes Test reliability established?: Not referenced or discussed Statistical tests used: Chi-square, Fishers’s exact test, MannWhitney, t-test, Se/Sp Blinding: Not described Definition of positive and negative on screening test: Gray-scale ultra sound: (Sassone’s criteria) • Solid or mixed 

solid/cystic 

• Faded borders • Septae > 3 mm • Solid papillary 

projections into cyst 

Age: Range: 15-88 Mean for patients with benign lesions: 42.6 (12.3) Mean for patients with malignant lesions: 53.1 (12.6) Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: NR Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: Premenopausal US on day 7-8 Stage I: 20/74 (27%) Stage II: 9/74 (12.2%) Stage III: 42/74 (56.7%) Stage IV: 3/74 (4.1%) 

1) TVUS, morphology only 

 Dis+ Dis- Tot T+ 64 83 147 

T- 10 172 182 Tot 74 255 329  Lower Upper  Value 95% CI 95% CI Se 86.5% 78.7% 94.3% Sp 67.5% 61.8% 73.2% 

PPV 43.6% 35.6% 51.6% NPV 94.5% 91.2% 97.8% 

2) Color Doppler (unclear if test characteristics calculated based on Doppler alone, or Doppler plus morphology) 

 Dis+ Dis- Tot T+ 69 14 83 

T- 5 241 246 Tot 74 255 329  Lower Upper  Value 95% CI 95% CI Se 93.2% 87.5% 98.9% Sp 94.5% 91.7% 97.3% 

PPV 83.1% 75.0% 91.2% NPV 98.0% 96.2% 99.7% 

Comme--Clinica--Unclecomparindepen--Uncle“Dopplevasculasemiquamount scale)” Quality ReferenVerificaTest reSample testing charactStatisticcomparBlindingDefinitio - (resis

but not used) 
D-182

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

cavity > 3 mm 

• > 50 mm free fluid in 

cul de sac 

Color Doppler: RI < 0.5 Other criteria included presence of “intense” angiogenesis within septae or solid parts of tumor, but unclear how this was used in determining benign vs malignant 

Schelling, Braun, Kuhn, et al., 2000 #2770 

Geographical location: Munich, Germany Dates: NR 

Size of population: 63 in development set; 257 in validation set Other Development and validation Reference standard: Surgery/pathology Reference standard applied to all test negatives?: Yes Test reliability established?: Discussed Statistical tests used: Logistic regression for development; Se/Sp for validation 

Age: NR Menopausal status (n [%]): Pre (< 45): 166 (64.6%) Post (> 55): 91 (35.4%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: NR Exclusion criteria: History of malignancy 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Ultrasound (any solid component = positive), all patients 

 Dis+ Dis- Tot T+ 38 42 80 

T- 1 176 177 Tot 39 218 257  Lower Upper  Value 95% CI 95% CI Se 97.4% 92.5% 100.0%Sp 80.7% 75.5% 86.0% PPV 47.5% 36.6% 58.4% NPV 99.4% 98.3% 100.0%

2) Ultrasound, any solid component, premenopausal 

 Dis+ Dis- Tot T+ 10 25 35 T- 1 130 131 Tot 11 155 166  Lower Upper  Value 95% CI 95% CI Se 90.9% 73.9% 100.0%Sp 83.9% 78.1% 89.7% PPV 28.6% 13.6% 43.5% NPV 99.2% 97.7% 100.0%

Comme--Clinica--Criterdescrib--For m65 can predictistable/va predicthe DopvariableQuality ReferenVerificaTest reSample StatisticBlindingDefinitio+ 
D-183

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

Blinding: Yes Definition of positive and negative on screening test: Solid component on morphology, presence of central vascularization on Doppler 

3) Utrasound, any solid component, postmenopausal 

 Dis+ Dis- Tot T+ 28 17 45 

T- 0 46 46 Tot 28 63 91  Lower Upper  Value 95% CI 95% CI Se 100.0% 89.3% 100.0%Sp 73.0% 62.1% 84.0% PPV 62.2% 48.1% 76.4% NPV 100.0% 93.5% 100.0%

4) Central vascularity on Doppler in solid component, all patients 

 Dis+ Dis- Tot T+ 36 14 50 T- 3 204 207 Tot 39 218 257  Lower Upper  Value 95% CI 95% CI Se 92.3% 83.9% 100.0%Sp 93.6% 90.3% 96.8% PPV 72.0% 59.6% 84.4% NPV 98.6% 96.9% 100.0%

5) Central vascularity on Doppler in solid component, premenopausal 

 Dis+ Dis- Tot T+ 10 9 19 T- 1 146 147 Tot 11 155 166  Lower Upper  Value 95% CI 95% CI Se 90.9% 73.9% 100.0%Sp 94.2% 90.5% 97.9% PPV 52.6% 30.2% 75.1% NPV 99.3% 98.0% 100.0%
D-184

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

6) Central vascularity on Doppler in solid component, postmenopausal 

 Dis+ Dis- Tot T+ 26 5 31 

T- 2 58 60 Tot 28 63 91  Lower Upper  Value 95% CI 95% CI Se 92.9% 83.3% 100.0%Sp 92.1% 85.4% 98.7% PPV 83.9% 70.9% 96.8% NPV 96.7% 92.1% 100.0%

Schneider, Schneider, Reed, et al., 1993 #4830 

Geographical location: Arizona, USA Academic Center Dates: NR 

Size of population: 55 women Other “Cross-sectional” referral Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Sasonne ? Granberg RI - yes Statistical tests used: 

Age: Mean: 53 Median: 53 Range: 10-79 Menopausal status (n [%]): Pre: 22 (40%) Post: 33 (60%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Women referred to OB/Gyn department with diagnosis of mass and scheduled for surgery already Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): All patients had ultrasound finding of adnexal mass Combination (n [%]): NR Additional data used for diagnosis: NR 

1) RI ≤ 0.8 

 Dis+ Dis- Tot T+ 15 17 32 

T- 1 22 23 Tot 16 39 55  Lower Upper  Value 95% CI 95% CI Se 93.8% 81.9% 100.0%Sp 56.4% 40.8% 72.0% PPV 46.9% 29.6% 64.2% NPV 95.7% 87.3% 100.0%

2) Granberg et al method US 

 Dis+ Dis- Tot T+ 14 6 20 T- 2 33 35 Tot 16 39 55  Lower Upper  Value 95% CI 95% CI Se 87.5% 71.3% 100.0%Sp 84.6% 73.3% 95.9% 

PPV 70.0% 49.9% 90.1% NPV 94.3% 86.6% 100.0%

Comme--RI cut(not pro--RI ≤ 0(1.0) Quality ReferenVerificaTest re+ for CA? for otSample StatisticBlindingDefinitio+/- 
D-185

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

Se, Sp Blinding: Yes Definition of positive and negative on screening test: Sasonne’s score Granberg [5] method of 2D US RI ≤ 0.8 CA-125 > 35 U/ml 

3) Sasonne (cut off 9) 

 Dis+ Dis- Tot T+ 14 10 24 

T- 2 29 31 Tot 16 39 55  Lower Upper  Value 95% CI 95% CI Se 87.5% 71.3% 100.0%Sp 74.4% 60.7% 88.1% 

PPV 58.3% 38.6% 78.1% NPV 93.5% 84.9% 100.0%

4) CA-125 > 35 U/ml 

 Dis+ Dis- Tot T+ 12 6 18 

T- 4 33 37 Tot 16 39 55  Lower Upper  Value 95% CI 95% CI Se 75.0% 53.8% 96.2% Sp 84.6% 73.3% 95.9% 

PPV 66.7% 44.9% 88.4% NPV 89.2% 79.2% 99.2% 
D-186

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommSchutter, Davelaar, van Kamp, et al., 2002 #2160 

Geographical location: Amsterdam and Enschede, The Netherlands Dates: Nov 1990-Dec 

1992 Size of population: 511; serum available for 412 Other Serum bank Reference standard: Surgery/pathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: Se/Sp; logistic regression Blinding: Yes Definition of positive and negative on screening test: Varied; “optimal” cutpoints CA-125: 57 u/mL CA-15-3: 26 u/mL CA-724: 3. 5 u/mL 

Age: NR Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: NR Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) CA-125, ovarian cancer vs benign ovarian mass, threshold = 35 u/mL 

 Dis+ Dis- Tot T+ 108 35 143 

T- 25 94 119 Tot 133 129 262  Lower Upper  Value 95% CI 95% CI Se 81.0% 74.3% 87.7% Sp 73.0% 65.3% 80.7% 

PPV 75.6% 68.5% 82.6% NPV 78.8% 71.5% 86.2% 

2) CA-125, ovarian cancer vs benign ovarian mass, threshold = 57 u/mL 

 Dis+ Dis- Tot T+ 102 23 126 

T- 31 106 136 Tot 133 129 262  Lower Upper  Value 95% CI 95% CI Se 77.0% 69.8% 84.2% Sp 82.0% 75.4% 88.6% 

PPV 81.5% 74.7% 88.3% NPV 77.6% 70.6% 84.6% 

3) CA-15-3, ovarian cancer vs benign mass, threshold = 26 u/mL 

 Dis+ Dis- Tot T+ 82 9 91 

T- 51 120 171 Tot 133 129 262  Lower Upper  Value 95% CI 95% CI Se 62.0% 53.8% 70.2% Sp 93.0% 88.6% 97.4% 

PPV 90.1% 84.0% 96.2% NPV 70.4% 63.5% 77.2% 

Comme--ClinicaQuality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-187

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

4) CA-724, Ovarian cancer vs benign ovarian mass, threshold = 3.5 u/mL 

 Dis+ Dis- Tot T+ 84 18 102 

T- 49 111 160 Tot 133 129 262  Lower Upper  Value 95% CI 95% CI Se 63.0% 54.8% 71.2% Sp 86.0% 80.0% 92.0% 

PPV 82.3% 74.9% 89.7% NPV 69.3% 62.1% 76.4% 

5) CA-125, all malignancy vs all benign, threshold = 35 u/mL 

 Dis+ Dis- Tot T+ 136 41 177 

T- 90 130 220 Tot 226 171 397  Lower Upper  Value 95% CI 95% CI Se 60.0% 53.6% 66.4% Sp 76.0% 69.6% 82.4% 

PPV 76.8% 70.5% 83.0% NPV 59.0% 52.5% 65.5% 

6) CA-125, all malignancy vs all benign, threshold = 57 u/mL 

 Dis+ Dis- Tot T+ 118 27 145 

T- 108 144 252 Tot 226 171 397  Lower Upper  Value 95% CI 95% CI Se 52.0% 45.5% 58.5% Sp 84.0% 78.5% 89.5% 

PPV 81.1% 74.7% 87.5% NPV 57.0% 50.9% 63.1% 
D-188

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

7) CA 15-3, all malignancy vs all benign, threshold = 26 u/mL 

 Dis+ Dis- Tot T+ 106 15 122 

T- 120 156 275 Tot 226 171 397  Lower Upper  Value 95% CI 95% CI Se 47.0% 40.5% 53.5% Sp 91.0% 86.7% 95.3% 

PPV 87.3% 81.4% 93.3% NPV 56.5% 50.7% 62.4% 

8) CA-724, all malignancy vs all benign, threshold = 3.5 U/mL 

 Dis+ Dis- Tot T+ 118 27 145 

T- 108 144 252 Tot 226 171 397  Lower Upper  Value 95% CI 95% CI Se 52.0% 45.5% 58.5% Sp 84.0% 78.5% 89.5% 

PPV 81.1% 74.7% 87.5% NPV 57.0% 50.9% 63.1% 
D-189

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommSchutter, Kenemans, Sohn, et al., 1994 #940 

Geographical location: Amsterdam, The Netherlands; and Heidelberg, Koln, Wurzburg, and Ulm, Germany Dates: Nov 1990-Dec 

1992 Size of population: 276; 48 excluded (13 45 years old or less, 16 not amenorrheic for 12 months, 4 no path dx, 14 additional malignancy, 10 indeterminate pelvic exam, 3 no preop CA125), for total of 228 Other Multicenter, prospective, patients referred for pelvic mass Reference standard: Surgery/pathology Reference standard applied to all test negatives?: Yes Test reliability established?: Not referenced or discussed Statistical tests used: Se/Sp; logistic regression Blinding: No Definition of positive 

Age: Mean: 63 Range: 45-88 Menopausal status (n [%]): 100% postmenopausal Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: 45 years old Amenorrheic > 12 months Schedule for surgery with tissue diagnosis No history of bilateral oophorectomy or additional cancer Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): 199 (87.3%) Detected by imaging (n [%]): 28 (12.7%) Combination (n [%]): NR Additional data used for diagnosis: Stage distribution: I: 16/72 (22.2%) II: 7/72 (9.7%) III: 34/72 (47.2%) IV: 15/72 (20.8%) 

Borderline tumors (n = 6) not included 1) CA-125 > 35 U/ml 

 Dis+ Dis- Tot T+ 68 25 93 

T- 27 102 129 Tot 95 127 222  Lower Upper  Value 95% CI 95% CI Se 71.6% 62.5% 80.6% Sp 80.3% 73.4% 87.2% PPV 73.1% 64.1% 82.1% NPV 79.1% 72.0% 86.1% 

2) Ultrasound: Finkler score > 7 (as described) 

 Dis+ Dis- Tot T+ 84 46 130 T- 11 81 92 Tot 95 127 222  Lower Upper  Value 95% CI 95% CI Se 88.4% 82.0% 94.9% Sp 63.8% 55.4% 72.1% PPV 64.6% 56.4% 72.8% NPV 88.0% 81.4% 94.7% 

Comme--Clinica(symptoQuality ReferenVerificaTest reSample StatisticBlindingDefinitio
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

and negative on screening test: Ultrasound: Positive if multiseptated or irregular cystic mass “consistent in appearance with ovarian tumor; or presence of ascites CA-125: > 35 U/mL 

Schutter, Sohn, Kristen, et al., 1998 #730 

Geographical location: Germany Dates: NR 

Size of population: 155 women Other Unclear Reference standard: Histology Reference standard applied to all test negatives?: Yes Test reliability established?: For pelvic exam – No CA-125 – Yes CA-72-4 - ? (mostly in gastric CA) they set own cutoff point here US - Yes Statistical tests used: Chi-square ROC Logistic regression Blinding: 

No

Age: Mean: 63 Median: 61 Range: 45-88 Menopausal status (n [%]): Post (> 55): 155 (100%) Race/ethnicity (n [%]): NR (assume 100% white) Risk factors (n [%]): NR Inclusion criteria: NR (see citation 25) Exclusion criteria: 

NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) PE 

 Dis+ Dis- Tot T+ 54 24 78 

T- 5 68 73 Tot 59 92 151  Lower Upper  Value 95% CI 95% CI Se 91.5% 84.4% 98.6% Sp 73.9% 64.9% 82.9% PPV 69.2% 59.0% 79.5% NPV 93.2% 87.4% 98.9% 

2) US 

 Dis+ Dis- Tot T+ 51 28 79 T- 8 64 72 Tot 59 92 151  Lower Upper  Value 95% CI 95% CI Se 86.4% 77.7% 95.2% Sp 69.6% 60.2% 79.0% PPV 64.6% 54.0% 75.1% NPV 88.9% 81.6% 96.1% 

3) CA-125 ≥ 35 U/ml 

 Dis+ Dis- Tot T+ 41 15 56 T- 18 77 95 Tot 59 92 151 

Comme--Bordefrom 2x--Note “paramesystem --FinkleQuality ReferenVerificamany nTest reU/S, CASample StatisticBlindingDefinitio
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

Definition of positive and negative on screening test: Table 1 Exam – clinical impression of malignancy US – Finkler Score 7-10 CA-125 - ≥ 35 U/ml 

 Lower Upper  Value 95% CI 95% CI Se 69.5% 57.7% 81.2% 

Sp 83.7% 76.1% 91.2% PPV 73.2% 61.6% 84.8% NPV 81.1% 73.2% 88.9% 

Scoutt, McCarthy, Lange, et al., 1994 #4530 

Geographical location: New Haven, CT Dates: 1988-1990 

Size of population: 103 patients with 121 masses; data provided on 120 Other Case series Reference standard: Surgery Reference standard applied to all test negatives?: No; 11 with “classic” leiomyomas, 2 with “no mass’ Test reliability established?: Not referenced or discussed Statistical tests used: Se/Sp Blinding: Yes Definition of positive 

Age: Median: 40 Range: 2-87 Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: NR Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Data provided for mass, not patient MRI, malignant vs. benign; threshold for positive MR = indeterminate or malignant 

 Dis+ Dis- Tot T+ 21 11 32 

T- 1 87 88 Tot 22 98 120  Lower Upper  Value 95% CI 95% CI Se 95.5% 86.8% 100.0%Sp 88.8% 82.5% 95.0% PPV 65.6% 49.2% 82.1% NPV 98.9% 96.6% 100.0%

Comme--Clinica--LengtQuality ReferenVerificaTest reSample StatisticBlindingDefinitio
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

and negative on screening test: Malignancy: solid or highly complex, mural nodules, septations > 3 mm, ascites. Indeterminate if not definitely benign or malignant 

Sengoku, Satoh, Saitoh, et al., 1994 #4390 

Geographical location: Asahikawa, Japan Dates: Apr 1991-May 

1992 Size of population: 28 women Other Case series Reference standard: Surgery/pathology Reference standard applied to all test negatives?: Yes Test reliability established?: Discussed Statistical tests used: Se/Sp, t-test Blinding: No Definition of positive and negative on screening test: Ultrsound morphology 

Age: Mean (SD): 49 (15) Range: 19-80 Menopausal status (n [%]): Pre (< 45): 17 (60.7%) Post (> 55): 11 (39.3%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: NR Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) CA-125 > 35 U/ml, benign vs malignant 

 Dis+ Dis- Tot T+ 13 3 16 

T- 3 9 12 Tot 16 12 28  Lower Upper  Value 95% CI 95% CI Se 81.3% 62.1% 100.0%Sp 75.0% 50.5% 99.5% PPV 81.3% 62.1% 100.0%NPV 75.0% 50.5% 99.5% 

2) Ultrasound morphology 

 Dis+ Dis- Tot T+ 13 4 17 T- 3 8 11 Tot 16 12 28  Lower Upper  Value 95% CI 95% CI Se 81.3% 62.1% 100.0%Sp 66.7% 40.0% 93.3% PPV 76.5% 56.3% 96.6% NPV 72.7% 46.4% 99.0% 

3) Pulsatility index < 1.5 

 Dis+ Dis- Tot T+ 13 1 14 T- 3 11 14

Comme--Clinica--Small --No decomes Quality ReferenVerificaTest reSample StatisticBlindingDefinitio + 
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

Sassone system (referenced, not described) Pulsatility index: < 1.5 CA-125> > 35 

Tot 16 12 28 

 Lower Upper  Value 95% CI 95% CI Se 81.3% 62.1% 100.0%Sp 91.7% 76.0% 100.0%PPV 92.9% 79.4% 100.0%NPV 78.6% 57.1% 100.0%

Shabana and Onsrud, 1994 #4400 

Geographical location: Trondheim, Norway Dates: NR 

Size of population: 85 women Other – Case control Three groups compared in terms of serum markers:33 with ovarian Ca, 26 with benign pelvic masses, and 26 with normal pelvis Reference standard: Histopathology for all but those with “normal pelvis” which was assessed at laparoscopy Reference standard applied to all test negatives?: Yes Test reliability established?: Yes for CA-125 Statistical tests used: Se, Sp, ROC 

Age: NR Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: NR Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) CA-125 > 25 U/ml 

 Dis+ Dis- Tot T+ 26 2 28 

T- 4 24 28 Tot 30 26 56  Lower Upper  Value 95% CI 95% CI Se 86.7% 74.5% 98.8% Sp 92.3% 82.1% 100.0%PPV 92.9% 83.3% 100.0%NPV 85.7% 72.8% 98.7% 

Comme--Not pr--Only 2includeof this i--CA-12in text --Unclechosen Quality ReferenVerificaTest reSample StatisticBlindingDefinitio
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

Blinding: NR Definition of positive and negative on screening test: CA-125 > 25 U/ml 

Siegel, Dehdashti, Mutch, et al., 2003 #1960 

Geographical location: St Louis, MO; Houston, TX; Indianapolis, IN; Dates: NR 

Size of population: 35; 2 did not undergo surgery Other Validation Reference standard: Surgery Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: Se/Sp Blinding: Yes Definition of positive and negative on screening test: “Focal increased uptake of radiotracer at sites not 

Age: Mean: 55 Range: 31-78 Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: NR Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Results provided only for newly diagnosed pelvic masses (n = 26) Borderline excluded (faint uptake by 1 reader, none by other) 

 Dis+ Dis- Tot T+ 7 4 11 

T- 0 14 14 Tot 7 18 25  Lower Upper  Value 95% CI 95% CI Se 100.0% 57.1% 100.0%Sp 77.8% 58.6% 97.0% PPV 63.6% 35.2% 92.1% NPV 100.0% 78.6% 100.0%

Specificity increased to 82% when re-read with clinical information available 

Comme--Clinica--Not a Quality ReferenVerificaTest reSample StatisticBlindingDefinitio
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

corresponding to obvious normal anatomic structures” 

Smikle, Lunt, and Hankins, 1995 #6290 

Geographical location: USA Dates: Jun 1990 – Aug 

1992 Size of population: 195 Retrosceptive case seriesReference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: Fisher exact test Blinding: NR Definition of positive and negative on screening test: CA-125 >= 35 U/ml 

Age: Those with benign lesions: mean age – 45 (14.7) Those with malignant lesions: mean – 56.9 (13.9) Menopausal status (n [%]): Not clear for those for whom CA-125 was available (n = 100) 50 were > 50 years old and 50 were <=50 Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Chart review of all cases with operative reports of “rule-out malignancy” “pelvic mass” “adnexal mass” in time frame Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) CA-125 >= 35 U/ml in postmenopausal women (age >50) 

 Dis+ 5 Tot T+ 11 26 37 

T- 2 32 34 Tot 13 58 71  Lower Upper  Value 95% CI 95% CI Se 84.6% 65.0% 100.0%Sp 55.2% 42.4% 68.0% PPV 29.7% 15.0% 44.5% NPV 94.1% 86.2% 100.0%

2) CA-125 in women <= 50 

 Dis+ 5 Tot T+ 2 12 14 T- 0 36 36 Tot 2 48 50  Lower Upper  Value 95% CI 95% CI Se 100.0% -50.0% 100.0%Sp 75.0% 62.8% 87.3% PPV 14.3% 0.0% 32.6% NPV 100.0% 91.7% 100.0%

3) CA-125 for all women combined 

 Dis+ 5 Tot T+ 13 17 30 T- 2 68 70 Tot 15 85 100  Lower Upper  Value 95% CI 95% CI Se 86.7% 69.5% 100.0%Sp 80.0% 71.5% 88.5% 

Comme--Bordemaligna--Of 19had CA--State distinguhowevecould b--Not reabdomiQuality ReferenVerificaTest reSample StatisticBlindingDefinitio
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

PPV 43.3% 25.6% 61.1% NPV 97.1% 93.2% 100.0%

Sohaib, Mills, Sahdev, et al., 2005 #7430 

Geographical location: UK Dates: NR 

Size of population: 89, however only data for 72 Prospective case series

Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: ROC curves Student’s t-test Mann-Whitney U test Chi square Blinding: Yes Definition of positive and negative on screening test: US – morphology and RI and PI were noted and a “subjective assessment was made as to whether each mass was benign or malignant” and then 

Age: Mean: 53 Range: 19-86 Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Referral to hospital for adnexal mass in time frame Exclusion criteria: 

NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) US 

 Dis+ Dis- Tot T+ 29 26 55 

T- 0 17 17 Tot 29 43 72  Lower Upper  Value 95% CI 95% CI Se 100.0% 89.7% 100.0%Sp 39.5% 24.9% 54.1% 

PPV 52.7% 39.5% 65.9% NPV 100.0% 82.4% 100.0%

2) MRI 

 Dis+ Dis- Tot T+ 28 7 35 

T- 1 36 37 Tot 29 43 72  Lower Upper  Value 95% CI 95% CI Se 96.6% 90.0% 100.0%Sp 83.7% 72.7% 94.7% 

PPV 80.0% 66.7% 93.3% NPV 97.3% 92.1% 100.0%

Comme--Bordemaligna--Se, Showevecutpoinenough authors MRI pecases w- TVUS unable Quality ReferenVerificaTest reSample StatisticBlindingDefinitio
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

assigned to groups: 1) benign, 2) probably benign, 3) possibly malignant, 4) probably malignant, 5) malignant For Se and Sp calcs, groups 1 and 2 were evaluated together as were 3, 4, 5. MRI – classified into malignant or benign by radiologist “impression” and into same 5 categories. 

Soper, Hunter, Daly, et al., 1990 #6590 

Geographical location: Durham, NC Dates: Jan 1985-Jan 

1986 Size of population: 100 women Other Single center Prospective series Reference standard: Pathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes (reference) Statistical tests used: NR Blinding: Assays done after 

Age: NR Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: “Diagnostic laparotomy for pelvic mass” Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) CA-125—All malignancies, > 35 U/mL as threshold 

 Dis+ Dis- Tot T+ 38 14 52 

T- 16 32 48 Tot 54 46 100  Lower Upper  Value 95% CI 95% CI Se 70.4% 58.2% 82.5% Sp 69.6% 56.3% 82.9% PPV 73.1% 61.0% 85.1% NPV 66.7% 53.3% 80.0% 

2) CA-125—ovarian cancer, > 35 U/mL as threshold 

 Dis+ Dis- Tot T+ 38 22 60 T- 4 36 40 Tot 42 58 100  Lower Upper  Value 95% CI 95% CI Se 90.5% 81.6% 99.4% Sp 62.1% 49.6% 74.6% PPV 63.3% 51.1% 75.5% NPV 90.0% 80.7% 99.3% 

Comme--Unclepatients --Clinica--BordemalignaQuality ReferenVerificaTest reSample StatisticBlindingDefinitio N/AS 
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

surgery Definition of positive and negative on screening test: 

3) CA-125—All malignancies, > 65 U/ml as threshold 

 Dis+ Dis- Tot T+ 42 8 50 

T- 12 38 50 Tot 54 46 100  Lower Upper  Value 95% CI 95% CI Se 77.8% 66.7% 88.9% Sp 82.6% 71.7% 93.6% PPV 84.0% 73.8% 94.2% NPV 76.0% 64.2% 87.8% 

4) CA-125---Ovarian cancer, > 65 U/ml as threshold 

 Dis+ Dis- Tot T+ 35 15 50 T- 7 43 50 Tot 42 58 100  Lower Upper  Value 95% CI 95% CI Se 83.3% 72.1% 94.6% Sp 74.1% 62.9% 85.4% PPV 70.0% 57.3% 82.7% NPV 86.0% 76.4% 95.6% 

5) TAG-72---Ovarian cancer 

 Dis+ Dis- Tot T+ 21 4 25 T- 21 54 75 Tot 42 58 100  Lower Upper  Value 95% CI 95% CI Se 50.0% 34.9% 65.1% Sp 93.1% 86.6% 99.6% PPV 84.0% 69.6% 98.4% NPV 72.0% 61.8% 82.2% 
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

6) CA-15-3—Ovarian cancer 

 Dis+ Dis- Tot T+ 23 11 34 

T- 19 47 66 Tot 42 58 100  Lower Upper  Value 95% CI 95% CI Se 54.8% 39.7% 69.8% Sp 81.0% 70.9% 91.1% PPV 67.6% 51.9% 83.4% NPV 71.2% 60.3% 82.1% 

Results not reported separately, but CA-125 > 65 sensitivity of 79%, specificity of 86% in patients > 50. 

Stein, Laifer-Narin, Johnson, et al., 1995 #4280 

Geographical location: Los Angeles, CA Dates: Jul 1992-Feb 

1993 Size of population: 161 patients, 170 masses Other Single center series Reference standard: Surgery/pathology Reference standard applied to all test negatives?: Yes Test reliability established?: References provided Statistical tests used: 

Age: NR Menopausal status (n [%]): Pre (< 45):114 (70.8%) Post (> 55): 39 (24.2%) 8 (4.9%) post hysterectomy Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: NR Exclusion criteria: Premenopausal with simple or hemorrhagic cysts that resolved on followup, or if examined on any day other than days 3-10 of menstrual cycle; 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Ultrasound morphology (transvaginal in all but 23) 

 Dis+ Dis- Tot T+ 46 47 93 

T- 1 76 77 Tot 47 123 170  Lower Upper  Value 95% CI 95% CI Se 97.9% 93.7% 100.0%Sp 61.8% 53.2% 70.4% PPV 49.5% 39.3% 59.6% NPV 98.7% 96.2% 100.0%

2) Color Doppler-internal flow within solid component or septation 

 Dis+ Dis- Tot T+ 36 38 74 T- 11 85 96 Tot 47 123 170  Lower Upper  Value 95% CI 95% CI Se 76.6% 64.5% 88.7% 

Comme--Denomexclude--Resulmenopa--Analymasses Quality ReferenVerificaTest reSample StatisticBlindingDefinitio
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

Mann-Whitney Blinding: Unclear if radiologists were blinded to clinical data Definition of positive and negative on screening test: PI < 1.0 RI < 0.4 Morphology: suggestive of malignancy if complex cystic with solid mural nodules, complex cystic with thick septations ≥ 3 mm, predominately solid, or solid 

corpus luteum cyst on pathology; masses determined to arise from uterus on ultrasound 

Sp 69.1% 60.9% 77.3% PPV 48.6% 37.3% 60.0% NPV 88.5% 82.2% 94.9% 

3) Spectral Doppler—pulsatility index < 1.0 

 Dis+ Dis- Tot T+ 31 42 73 

T- 16 81 97 Tot 47 123 170  Lower Upper  Value 95% CI 95% CI Se 67.0% 53.6% 80.4% Sp 66.0% 57.6% 74.4% 

PPV 42.5% 31.1% 53.8% NPV 83.5% 76.1% 90.9% 

4) Spectral Doppler—resistive index < 0.4 

 Dis+ Dis- Tot T+ 11 12 23 

T- 36 111 147 Tot 47 123 170  Lower Upper  Value 95% CI 95% CI Se 23.4% 11.3% 35.5% Sp 90.2% 85.0% 95.5% PPV 47.8% 27.4% 68.2% NPV 75.5% 68.6% 82.5% 
D-201

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommStrigini, Gadducci, Del Bravo, et al., 1996 #4000 

Geographical location: Pisa, Italy Dates: Jan 1993-June 

1994 Size of population: 109 women Other Case series Reference standard: Surgery Reference standard applied to all test negatives?: Yes Test reliability established?: No Statistical tests used: Mann-Whitney U test, chi-square Blinding: Unclear Definition of positive and negative on screening test: Ultrasound: solid, irregular structure, thick septae, irregular margins Doppler: PI < 1 CA-125: > 65 U/mL 

Age: Median: 43 Range: 18-80 Menopausal status (n [%]): Pre (< 45): 75 (69%) Post (> 55): 34 (31%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Not clearly described Consecutive patients scheduled for laparotomy for adnexal mass in time frame Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: “Most” premenopausal women followed over several menstrual cycles to rule out functional cyst 

1) Ultrasound: Premenopausal 

 Dis+ Dis- Tot T+ 6 2 8 

T- 0 67 67 Tot 6 69 75  Lower Upper  Value 95% CI 95% CI Se 100.0% 40.0% 100.0%Sp 97.1% 93.1% 100.0%PPV 75.0% 45.0% 100.0%NPV 100.0% 92.0% 100.0%

2) Ultrasound: Postmenopausal 

 Dis+ Dis- Tot T+ 10 2 12 T- 3 19 22 Tot 13 21 34  Lower Upper  Value 95% CI 95% CI Se 76.9% 54.0% 99.8% Sp 90.5% 77.9% 100.0%PPV 83.3% 62.2% 100.0%NPV 86.4% 72.0% 100.0%

3) Ultrasound: Combined pre and post 

 Dis+ Dis- Tot T+ 16 4 20 T- 3 86 89 Tot 19 90 109  Lower Upper  Value 95% CI 95% CI Se 84.2% 67.8% 100.0%Sp 95.6% 91.3% 99.8% PPV 80.0% 62.5% 97.5% NPV 96.6% 92.9% 100.0%

4) Doppler: Premenopausal 

Comme--Clinica--Uncleresoluti--US crreproduvariabilQuality ReferenVerificaTest reSample StatisticBlindingDefinitio
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

 Dis+ Dis- Tot T+ 5 19 24 

T- 1 50 51 Tot 6 69 75  Lower Upper  Value 95% CI 95% CI Se 83.3% 53.5% 100% Sp 72.5% 61.9% 83.0% PPV 20.8% 4.6% 37.1% NPV 98.0% 94.2% 100% 

5) Doppler: Postmenopausal 

 Dis+ Dis- Tot T+ 11 4 15 T- 2 17 19 Tot 13 21 34  Lower Upper  Value 95% CI 95% CI Se 84.6% 65.0% 100% Sp 81.0% 64.2% 97.7% PPV 73.3% 51.0% 95.7% NPV 89.5% 75.7% 100% 

6) Doppler: pre and post combined 

 Dis+ Dis- Tot T+ 16 23 39 T- 3 67 70 Tot 19 90 109  Lower Upper  Value 95% CI 95% CI Se 84.2% 67.8% 100.0%Sp 74.4% 65.4% 83.5% PPV 41.0% 25.6% 56.5% NPV 95.7% 91.0% 100.0%

7) CA-125: Premenopausal 

 Dis+ Dis- Tot T+ 3 7 10 T- 3 62 65
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

Tot 6 69 75 

 Lower Upper  Value 95% CI 95% CI Se 50.0% 10.0% 90.0% Sp 89.9% 82.7% 97.0% PPV 30.0% 1.6% 58.4% NPV 95.4% 90.3% 100.0%

8) CA-125: Postmenopausal 

 Dis+ Dis- Tot T+ 8 2 10 T- 5 19 24 Tot 13 21 34  Lower Upper  Value 95% CI 95% CI Se 61.5% 35.1% 88.0% Sp 90.5% 77.9% 100% PPV 80.0% 55.2% 100% NPV 79.2% 62.9% 95.4% 

9) CA-125: combined 

 Dis+ Dis- Tot T+ 77 9 86 T- 8 81 89 Tot 85 90 175  Lower Upper  Value 95% CI 95% CI Se 90.6% 84.4% 96.8% Sp 90.0% 83.8% 96.2% PPV 89.5% 83.1% 96.0% NPV 91.0% 85.1% 97.0% 
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommSzpurek, Moszyniki, and Sajdak, 2004 #1530 

Geographical location: Poland Dates: NR 

Size of population: 464 women Case series

Reference standard: Pathology Reference standard applied to all test negatives?: Yes

Test reliability established?: 

NoStatistical tests used: Se, Sp, ROC Blinding: NoDefinition of positive and negative on screening test: DS index ≥ 4 Doppler Subjective Index 

Age: Pre-menopause: Mean (SD): 37.4 (9.7) Post-menopause: Mean (SD): 63.4 (8.7) Menopausal status (n [%]): Pre: 363 (78%) Post: 101 (22%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Women undergoing surgery for ovarian mass who had had Doppler u/s done at the hospital Exclusion criteria: 

NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: DS index 1 point given for each of the following: Number of vessels (≥ 5) 

Location of vessels (in septae, in papillae or solid parts) Arrangement of vessels (Irregular, random) Shape of velocity waves (smooth; low waveform amplitude) Presence of protodiastolic notch (absent) 

1) Doppler index (cutoff DS ≥ 4) postmenopausal women only (n = 101)

 Dis+ Dis- Tot T+ 68 0 68 

T- 6 27 33 Tot 74 27 101  Lower Upper  Value 95% CI 95% CI Se 91.9% 85.7% 98.1% Sp 100.0% 88.9% 100.0%PPV 100.0% 95.6% 100.0%NPV 81.8% 68.7% 95.0% 

AUC = 0.9775 2) Doppler index (cutoff DS ≥ 4) all women (n = 464) 

 Dis+ Dis- Tot T+ 143 20 163 T- 22 279 301 Tot 165 299 464  Lower Upper  Value 95% CI 95% CI Se 86.7% 81.5% 91.9% Sp 93.3% 90.5% 96.1% 

PPV 87.7% 82.7% 92.8% NPV 92.7% 89.8% 95.6% 

AUC = 0.9315 3) Doppler index (cutoff DS ≥ 4) premenopause 

 Dis+ Dis- Tot T+ 75 20 95 

T- 16 252 268 Tot 91 272 363  Lower Upper  Value 95% CI 95% CI Se 82.4% 74.6% 90.2% Sp 92.6% 89.5% 95.7% 

Comme--Cut ofthis stuQuality ReferenVerificaTest reSample StatisticBlindingDefinitio
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

PPV 78.9% 70.7% 87.1% NPV 94.0% 91.2% 96.9% 

Tailor, Bourne, Campbell, et al., 2003 #1970 

Geographical location: UK Dates: NR 

Size of population: 2500 screened Screening study Reference standard: Histopathology or repeat US at between 12 weeks and six months depending on characteristic of first US and individual family history Reference standard applied to all test negatives?: No Test reliability established?: No for US Yes for CA-125 Statistical tests used: Se Sp, Posterior, prior oddss Blinding: Not described – but prospective study Definition of positive and negative on screening test: US – considered 

Age: Mean: 48 Range: 17-78 Menopausal status (n [%]): Pre (< 45): 1629 (65%) Post (> 55): 644 (26%) And 227(9%) were post hysterectomy Race/ethnicity (n [%]): NR Risk factors (n [%]): See below Inclusion criteria: Self-referred women in time frame for screening Women with at least 1 relative with ovarian cancer and another with another cancer Exclusion criteria: NR 

Symptomatic (n [%]): 0 (0%) Detected by exam (n [%]): 0 (0%) Detected by imaging (n [%]): 0 Combination (n [%]): NR Additional data used for diagnosis: NR 

1) US for the first screening episode 

 Dis+ 5 Tot T+ 6 76 82 

T- 1 2417 2418 Tot 7 2493 2500  Lower Upper  Value 95% CI 95% CI Se 85.7% 59.8% 100.0%Sp 97.0% 96.3% 97.6% PPV 7.3% 1.7% 13.0% NPV 100.0% 99.9% 100.0%

2) US for the second screening episode (n = 998) 

 Dis+ 5 Tot T+ 3 11 14 T- 0 984 984 Tot 3 995 998  Lower Upper  Value 95% CI 95% CI Se 100.0% 0.0% 100.0%Sp 98.9% 98.2% 99.5% PPV 21.4% 0.0% 42.9% NPV 100.0% 99.7% 100.0%

3) for >= 3rd screen episode (n = 733) 

 Dis+ 5 Tot T+ 2 6 8 

T- 0 725 725 Tot 2 731 733  Lower Upper  Value 95% CI 95% CI Se 100.0% -50.0% 100.0%Sp 99.2% 98.5% 99.8% 

Comme--Bordemaligna--Good specific organizpatient) --Meno--UnablCA-125 negativ--Subjeused --Inclusstudy p--TVUS Quality ReferenVerificaTest reSample StatisticBlindingDefinitio
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

abnormal is: “ovary enlarged (>95th centile), a 

cyst was detected, and areas of hypo- or hyperechogenicity were seen which were inconsistent with normalphysiology” CA-125 – range used 

PPV 25.0% 0.0% 55.0% NPV 100.0% 99.6% 100.0%

Takac, 1998 #3240 

Geographical location: Maribor, Slovenia Dates: Jan 1994-Dec 

1995 Size of population: 120 women Other Case series Reference standard: Surgery Reference standard applied to all test negatives?: Yes Test reliability established?: Yes; referenced and discussed Statistical tests used: Mann-Whitney Blinding: Not mentioned Definition of positive and negative on screening test: ROC done on varying 

Age: Overall not reported; mean age of patients with benignmasses 42 (13.5), malignant 53.3 (17.1) Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Adnexal mass that had surgery Exclusion criteria: Not undergoing surgery 

Symptomatic (n [%]): NR Detected by exam (n [%]): 120 (100%) had mass on examination in clinic—but unclear what initial presentation Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: Premenopausal US in follicular phase

1) Resistive index ≤ 0.4 

 Dis+ Dis- Tot T+ 32 2 34 

T- 7 76 83 Tot 39 78 117  Lower Upper  Value 95% CI 95% CI Se 82.1% 70.0% 94.1% Sp 97.4% 93.9% 100.0%PPV 94.1% 86.2% 100.0%NPV 91.6% 85.6% 97.5% 

3 patients with absent vascularization (2 benign, 1 malignant) excluded from analysis in paper; reported Se = 82%, Sp = 97% 

Quality ReferenVerificaTest reSample StatisticBlindingDefinitio
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

definitions for resistive index Both highest and lowest measured RI used in calculating final RI 

Tanir, Ozalp, Yalcin, et al., 2003 #1850 

Geographical location: Eskisehir, Turkey Dates: Aug 1991-Sept 

2002 Size of population: 63 women Other Case series Reference standard: Surgery/pathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: ROC Blinding: Yes Definition of positive and negative on screening test: Varied cutoff for VEGF, CA-125 

Age: Reported separately by diagnosis: Non-neoplastic 39.0 (2.0) Benign 42.2 (5.2) Malignant 56.9 (4.2) Menopausal status (n [%]): Pre (< 45): 40 (63%) Post (> 55): 23 (37%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: NR Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: Ultrasound (including Doppler) 

1) VEGF—threshold 68.7 

 Dis+ Dis- Tot T+ 11 6 17 

T- 1 44 45 Tot 12 50 62  Lower Upper  Value 95% CI 95% CI Se 92.0% 76.7% 100.0%Sp 88.0% 79.0% 97.0% 

PPV 64.7% 42.0% 87.4% NPV 97.8% 93.5% 100.0%

2) CA-125 ≥ 37 U/mL 

 Dis+ Dis- Tot T+ 11 23 34 

T- 1 27 28 Tot 12 50 62  Lower Upper  Value 95% CI 95% CI Se 92.0% 76.7% 100.0%Sp 54.0% 40.2% 67.8% 

PPV 32.4% 16.6% 48.1% NPV 96.4% 89.6% 100.0%

Comme--Clinica-- Bordemaligna--UnablmenopaPremen VEGF CA-12Postme VEGF CA-12ReportereporteuncertaQuality ReferenVerificaTest reSample StatisticBlindingDefinitio + 
D-208

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommTay and Chua, 1994 #4450 

Geographical location: Singapore Dates: Oct 1991 – Apr 

1992 Size of population: 105 women Other Prospective study of patients admitted to single center with mass for surgery Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: Se, Sp Blinding: Definition of positive and negative on screening test: CA-125 > 35 U/mL 

Age: Mean (SD): 38.6 (12.9) Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Patients admitted to hospital with diagnosis of “ovarian cysts” for elective surgery. Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): 105 (100%) Additional data used for diagnosis: NR 

1) Serum CA-125 > 35 U/ml 

 Dis+ Dis- Tot T+ 8 21 29 

T- 1 74 75 Tot 9 95 104  Lower Upper  Value 95% CI 95% CI Se 88.9% 68.4% 100.0%Sp 77.9% 69.6% 86.2% PPV 27.6% 11.3% 43.9% NPV 98.7% 96.1% 100.0%

Comme--Uncle(“cysts”--Study with uri--There reportePPV, athis stu22%...” reporteshould in our 2Quality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-209

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommTekay and Jouppila, 1992 #10970 

Geographical location: Finland Dates: NR 

Size of population: 72 Case series

Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: Se, Sp Mann-Whitney U test Blinding: Not mentioned but prospective Definition of positive and negative on screening test: RI <= 0.6 or 0.5 

Age: Premenopausal – mean 37 range 17-50 Post menopausal – mean age 60 range 42-74 Menopausal status (n [%]): Pre (< 45): 46 (63.9%) Post (> 55): 26(36.1%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Referral to hospital for adnexal mass who underwent surgery Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) RI <=0.6 

 Dis+ Dis- Tot T+ 9 17 26 

T- 2 44 46 Tot 11 61 72  Lower Upper  Value 95% CI 95% CI Se 82.0% 59.3% 100.0%Sp 72.0% 60.7% 83.3% PPV 34.6% 16.3% 52.9% NPV 95.7% 89.8% 100.0%

2) RI <+ 0.5 

 Dis+ Dis- Tot T+ 5 7 12 T- 6 54 60 Tot 11 61 72  Lower Upper  Value 95% CI 95% CI Se 46.0% 16.5% 75.5% Sp 89.0% 81.1% 96.9% 

PPV 41.7% 13.8% 69.6% NPV 90.0% 82.4% 97.6% 

Comme--Bordemaligna--Althoumorphoable to --Overlamaligna--68 exaabdomiresults Quality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-210

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommTepper, LernerGeva, Altaras, et al., 1995 #4090 

Geographical location: Kfar Saba, Israel Dates: 1990-1993 

Size of population: 217 women Other All patients admitted to hospital with mass for surgery Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes, by reference Statistical tests used: Se, Sp Blinding: NR Definition of positive and negative on screening test: RI cutoff of < 0.4 (literature standard) compared with 0.47 (study mean) and 0.53 (mean + 2SD) 

Age: Mean (SD): 44.3 Range: 8-79 Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Admitted to hospital for surgery for diagnosis of adnexal mass Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) RI (cutoff < 0.4), only considering patients in whom blood flow velocity waveforms could be detected, borderline tumors excluded 

 Dis+ Dis- Tot T+ 17 3 20 

T- 8 79 87 Tot 25 82 107  Lower Upper  Value 95% CI 95% CI Se 68.0% 49.7% 86.3% Sp 96.3% 92.3% 100.0%PPV 85.0% 69.4% 100.0%NPV 90.8% 84.7% 96.9% 

2) RI (cutoff < 0.4), borderline tumors counted as malignant 

 Dis+ Dis- Tot T+ 19 3 22 T- 33 162 195 Tot 52 165 217  Lower Upper  Value 95% CI 95% CI Se 36.5% 23.5% 49.6% Sp 98.2% 96.1% 100.0%PPV 86.4% 72.0% 100.0%NPV 83.1% 77.8% 88.3% 

3) RI (cutoff < 0.4) borderline tumors counted as benign 

 Dis+ Dis- Tot T+ 17 5 22 T- 21 174 195 Tot 38 179 217  Lower Upper  Value 95% CI 95% CI Se 44.7% 28.9% 60.5% Sp 97.2% 94.8% 99.6% 

Comme--To traabstraccould b--Uncle--InterodiscussTumors are not Authors patients wavefo25/38 (612/14 (882/165 Quality ReferenVerifica

Test reSample StatisticBlindingDefinitio
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

PPV 77.3% 59.8% 94.8% NPV 89.2% 84.9% 93.6% 

4) RI (cutoff < 0.47) 

 Dis+ Dis- Tot T+ 33 23 56 T- 5 142 147 Tot 38 165 203  Lower Upper  Value 95% CI 95% CI Se 86.8% 76.1% 97.6% Sp 86.1% 80.8% 91.3% PPV 58.9% 46.0% 71.8% NPV 96.6% 93.7% 99.5% 

5) RI (cutoff < 0.53) 

 Dis+ Dis- Tot T+ 38 43 81 T- 0 122 122 Tot 38 165 203  Lower Upper  Value 95% CI 95% CI Se 100.0% 92.1% 100.0%Sp 73.9% 67.2% 80.6% PPV 46.9% 36.0% 57.8% NPV 100.0% 97.5% 100.0%
D-212

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommTian, Zhang, Jiao, et al., 2000 #2670 

Geographical location: Beijing, China Dates: April 1996-Nov 

1998 Size of population: 71 women Other Case series Reference standard: Surgery/pathology Reference standard applied to all test negatives?: Yes Test reliability established?: Not referenced or discussed Statistical tests used: Chi-square, t-test Blinding: Yes; explicitly stated Definition of positive and negative on screening test: Grade 1 or 2 uptake of c99m, no move with peristalsis or volume change of bladder, or signs of intestinal, peritoneal, or lymphatic involvement 

Age: Benign Range: 15-72 Malignant Range: 25-70 Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Mass, scheduled for laparoscopy Exclusion criteria: NR 

Symptomatic (n [%]): “Most” had “no symptoms other than slight abdominal pain” Detected by exam (n [%]): 65 (91.5%; unclear if screening exam) Detected by imaging (n [%]): 28 (39.4%); MRI or CT Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Tc-99m 

 Dis+ Dis- Tot T+ 22 7 29 

T- 1 41 42 Tot 23 48 71  Lower Upper  Value 95% CI 95% CI Se 92.0% 80.9% 100.0%Sp 54.0% 39.9% 68.1% 

PPV 75.9% 60.3% 91.4% NPV 97.6% 93.0% 100.0%

2) CA-125 (>35 U/ml) 

 Dis+ Dis- Tot T+ 20 12 32 

T- 3 18 21 Tot 23 30 53  Lower Upper  Value 95% CI 95% CI Se 87.0% 73.2% 100.0%Sp 60.0% 42.5% 77.5% PPV 62.5% 45.7% 79.3% NPV 85.7% 70.7% 100.0%

3) CT-MRI 

 Dis+ Dis- Tot T+ 10 8 18 T- 3 7 10 Tot 13 15 28  Lower Upper  Value 95% CI 95% CI Se 76.9% 54.0% 99.8% Sp 46.7% 21.4% 71.9% PPV 55.6% 32.6% 78.5% NPV 70.0% 41.6% 98.4% 

Comme--Small --Differedifferen--Clinica--Explicblinded --No dediagnosbased oMRI or Quality ReferenVerificaTest reSample StatisticBlindingDefinitio+ 
D-213

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommTimmerman, Verrelst, Bourne, et al., 1999 #5940 

Geographical location: UK Dates: Aug 1994 – Aug 

1996 Size of population: 173 women Other Consecutive case series Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: Logistic regression ROC Se Sp Blinding: NR - prospective Definition of positive and negative on screening test: CA-125 ≥ 35 

Age: Mean: Pre 40 Post 64 Range: 22-93 Menopausal status (n [%]): Pre (< 45): 83 (48.0%) Post (> 55): 90 (52.0%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Prospective patients to get surgery for mass Exclusion criteria: 

No CA-125 preoperatively available 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) CA-125 ≥ 35 (borderline included as malignant) 

 Dis+ Dis- Tot T+ 39 23 62 

T- 10 101 111 Tot 49 124 173  Lower Upper  Value 95% CI 95% CI Se 79.6% 68.3% 90.9% Sp 81.5% 74.7% 88.3% 

PPV 62.9% 50.9% 74.9% NPV 91.0% 85.7% 96.3% 

2) CA-125 ≥ 35 (borderline included as benign) 

 Dis+ Dis- Tot T+ 34 27 61 

T- 10 102 112 Tot 44 129 173  Lower Upper  Value 95% CI 95% CI Se 77.3% 64.9% 89.7% Sp 79.1% 72.0% 86.1% PPV 55.7% 43.3% 68.2% NPV 91.1% 85.8% 96.4% 

Comme--ClinicaQuality ReferenVerificaTest reSample StatisticBlindingDefinitio+/- 
D-214

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommTimorTritsch, Lerner, Monteagudo, et al., 1993 #10840 

Geographical location: USA 

Dates: Apr 1991 – May 1992 Size of population: 93 patients 115 masses Case series

Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: Se, Sp Blinding: Not described but prospective Definition of positive and negative on screening test: Sassone scoring system Used (cutoff not mentioned but assume >= 9) RI < 0.46 PI < 0.62 

Age: Mean: 43.2 Range: 13-74 Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Presenting to hospital with diagnosis of mass in time frame Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Sassone morphologic criteria 

 Dis+ Dis- Tot T+ 11 9 20 

T- 1 61 62 Tot 12 70 82  Lower Upper  Value 95% CI 95% CI Se 93.7% 80.0% 100.0%Sp 87.1% 79.2% 95.0% 

PPV 55.0% 33.2% 76.8% NPV 98.4% 95.3% 100.0%

2) PI < 0.62 

 Dis+ Dis- Tot T+ 11 2 13 

T- 2 68 70 Tot 12 70 83  Lower Upper  Value 95% CI 95% CI Se 87.5% 68.8% 100.0%Sp 97.4% 93.7% 100.0%

PPV 84.6% 65.0% 100.0%NPV 97.1% 93.2% 100.0%

3) RI < 0.46 

 Dis+ Dis- Tot T+ 11 1 12 

T- 1 69 70 Tot 12 70 82  Lower Upper  Value 95% CI 95% CI Se 93.8% 80.2% 100.0%Sp 98.7% 96.0% 100.0%

PPV 91.7% 76.0% 100.0%NPV 98.6% 95.8% 100.0%

Comme--Excludmasses measur--Bordemaligna--RI and results cutpoin--Don’t Sassonoriginal --Clinica- -Althowas repindividuindividu--TVUS Quality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-215

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommTingulstad, Hagen, Skjeldestad, et al., 1996 #3890 

Geographical location: Norway Dates: Feb 1992 – Feb 

1994 Size of population: 173 women Other Consecutive patient series Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: Chi square, Se Sp, ROC Mann-Whitney U test Blinding: NR - prospective Definition of positive and negative on screening test: CA-125 – range US ≥ 2, where 

1 point assigned for each of the following: multilocular cystic lesion solid areas bilateral lesion ascites intra-abdominal ascites 

Age: NR Menopausal status (n [%]): Pre (< 45): 82 (47.4%) Post (> 55): 91 (52.6%) (defined as > 12 months amenorrhea or age > 50 if hysterectomy) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Age >30 with pelvic mass scheduled for surgery Exclusion criteria: 

NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) CA-125 > 25 U/ml 

 Dis+ Dis- Tot T+ 45 22 67 

T- 11 95 106 Tot 56 117 173  Lower Upper  Value 95% CI 95% CI Se 80.0% 69.5% 90.5% Sp 81.0% 73.9% 88.1% 

PPV 67.2% 55.9% 78.4% NPV 89.6% 83.8% 95.4% 

2) CA-125 > 50 U/ml 

 Dis+ Dis- Tot T+ 41 7 48 

T- 15 110 125 Tot 56 117 173  Lower Upper  Value 95% CI 95% CI Se 73.0% 61.4% 84.6% Sp 94.0% 89.7% 98.3% 

PPV 85.4% 75.4% 95.4% NPV 88.0% 82.3% 93.7% 

3) US score > 2 

 Dis+ Dis- Tot T+ 38 21 59 

T- 18 96 114 Tot 56 117 173  Lower Upper  Value 95% CI 95% CI Se 68.0% 55.8% 80.2% Sp 82.0% 75.0% 89.0% 

PPV 64.4% 52.2% 76.6% NPV 84.2% 77.5% 90.9% 

4) Menopausal status (postmenopausal = malignant) 

Comme--RMI s--No deQuality ReferenVerificaTest re/intraobSample StatisticBlindingDefinitio
D-216

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

 Dis+ Dis- Tot T+ 45 46 91 

T- 11 71 82 Tot 56 117 173  Lower Upper  Value 95% CI 95% CI Se 80.4% 70.0% 90.8% Sp 60.7% 51.8% 69.5% PPV 49.5% 39.2% 59.7% NPV 86.6% 79.2% 94.0% 

Torres, Derchain, Faundes, et al., 2002 #2170 

Geographical location: Sao Paulo, Brazil Dates: Jan 1996 – Mar 

1998 Size of population: 158 women Other Series Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: Se, Sp Regression Blinding: NR – but prospective 

Age: NR Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Pelvic mass who had surgery in time frame Exclusion criteria: Lung masses, Signs of hepatic or intraperitoneal mets 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) CA-125 > 35 U/ml 

 Dis+ Dis- Tot T+ 52 23 75 

T- 15 68 83 Tot 67 91 158  Lower Upper  Value 95% CI 95% CI Se 78.0% 68.1% 87.9% Sp 75.0% 66.1% 83.9% 

PPV 69.3% 58.9% 79.8% NPV 81.9% 73.6% 90.2% 

2) US score ≥ 2 

 Dis+ Dis- Tot T+ 55 30 85 

T- 12 61 73 Tot 67 91 158  Lower Upper  Value 95% CI 95% CI Se 82.0% 72.8% 91.2% Sp 67.0% 57.3% 76.7% 

PPV 64.7% 54.5% 74.9% NPV 83.6% 75.1% 92.1% 

3) US score ≥ 3 

Comme--RMI sgiven, rvarious --Unclefrom or done -No disQuality ReferenVerificaTest reUS - Sample StatisticBlindingprospecDefinitio+/- 
D-217

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

Definition of positive and negative on screening test: US score – range from other RMI literature (0-8) CA-125 - range 

 Dis+ Dis- Tot T+ 50 26 76 

T- 17 65 82 Tot 67 91 158  Lower Upper  Value 95% CI 95% CI Se 75.0% 64.6% 85.4% Sp 71.0% 61.7% 80.3% 

PPV 65.8% 55.1% 76.5% NPV 79.3% 70.5% 88.0% 

4) Menopausal status (menopausal = malignant) 

 Dis+ Dis- Tot T+ 49 28 77 

T- 18 63 81 Tot 67 91 158  Lower Upper  Value 95% CI 95% CI Se 73.0% 62.4% 83.6% Sp 69.0% 59.5% 78.5% 

PPV 63.6% 52.9% 74.4% NPV 77.8% 68.7% 86.8% 
D-218

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommTroiano, QuedensCase, and Taylor, 1997 #3680 

Geographical location: New Haven, CT Dates: 1991-1996 

Size of population: 144 women Other Case series Reference standard: Surgery (45); serial ultrasound (followup 1-6 years) Reference standard applied to all test negatives?: See above Test reliability established?: Not referenced or discussed Statistical tests used: Descriptive Blinding: No Definition of positive and negative on screening test: Solid components, thickened septation, nodules; Dopplers; no explicit scoring or cutpoint used. CA-125 ≥ 36 U/m; 

Age: NR Menopausal status (n [%]): Pre (< 45): 102 (70.8%) Post (> 55): 42 (29.2%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: NR Exclusion criteria: 

NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) CA-125 ≥ 36 U/ml 

 Dis+ Dis- Tot T+ 17 88 105 

T- 3 36 39 Tot 20 124 144  Lower Upper  Value 95% CI 95% CI Se 85.0% 69.4% 100.0%Sp 29.0% 21.0% 37.0% 

PPV 16.2% 9.1% 23.2% NPV 92.3% 83.9% 100.0%

2) CA-125 ≥ 36 U/ml, postmenopausal 

 Dis+ Dis- Tot T+ 10 25 35 

T- 0 7 7 Tot 10 32 42  Lower Upper  Value 95% CI 95% CI Se 100.0% 70.0% 100.0%Sp 21.9% 7.6% 36.2% PPV 28.6% 13.6% 43.5% NPV 100.0% 57.1% 100.0%

Comme--ReporconsisteTable 1 --Diagn--Unablultrasou--BordemalignaQuality ReferenVerificaTest reSample StatisticBlindingDefinitio - 
D-219

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommValentin, 1997 #6170 

Geographical location: Malmo, Sweden Dates: NR 

Size of population: 151 women Other Prospective study at university hospital of consecutive patients with adnexal mass scheduled for surgery Reference standard: Histopathology Reference standard applied to all test negatives?: Yes, but 49 were excluded for technical reasons Test reliability established?: Statistical tests used: Se, Sp, regression Blinding: NR Definition of positive and negative on screening test: 

Age: Mean: 47.8 Range: 20-90 Menopausal status (n [%]): Pre (< 45): 92 (62.9%) Post (> 55): 53 (37.1%) 6 women who had undergoing hysterectomy were classified a pre or post menopausal on the basis of age. Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: NR Exclusion criteria: 49 excluded for: uninterpretable US examinations (12), surgery canceled (replaced by laparoscopy) (5), biopsy with cytologic diagnosis (3), or clinical followup (22), myoma at time of surgery (7) 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) PI (cutoff < 1) 

 Dis+ Dis- Tot T+ 19 74 93 

T- 4 38 42 Tot 23 112 135  Lower Upper  Value 95% CI 95% CI Se 82.6% 67.1% 98.1% Sp 33.9% 25.2% 42.7% PPV 20.4% 12.2% 28.6% NPV 90.5% 81.6% 99.4% 

2) Color lakes visible on Doppler 

 Dis+ Dis- Tot T+ 21 42 63 T- 3 85 88 Tot 24 127 151  Lower Upper  Value 95% CI 95% CI Se 87.5% 74.3% 100.0%Sp 66.9% 58.7% 75.1% PPV 33.3% 21.7% 45.0% NPV 96.6% 92.8% 100.0%

3) Menopausal status (post =T+) 

 Dis+ Dis- Tot T+ 19 5 24 T- 37 90 127 Tot 56 95 151  Lower Upper  Value 95% CI 95% CI Se 33.9% 21.5% 46.3% Sp 94.7% 90.2% 99.2% PPV 79.2% 62.9% 95.4% NPV 70.9% 63.0% 78.8% 

Multiple logistic regression model constructed for multilocular solid tumors – 

Comme--Negatdiagnos(7) --Unclediagnosexclude--LMP tmaligna--VisibilevaluatreliabilitQuality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-220

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

results not reported here. 

Valentin, 1999b #3100 

Geographical location: Malmo, Sweden Dates: NR 

Size of population: 173 women Other Series Reference standard: Pathology Reference standard applied to all test negatives?: Yes Test reliability established?: No Statistical tests used: Chi-square Blinding: No Definition of positive and negative on screening test: Morphology: solid components Lerner score: ≥ 3 

Color score: ≥ 40 or 65 Pulsatility < 1.0 Resistive index < 0.4 Time-averaged max velocity: ≥ 7.2 cm/s Peak systolic velocity: ≥

14.4 cm/s 

Age: NR Menopausal status (n [%]): Pre (< 45): 98 (59.5%) Peri (45-55): Post (> 55): 70 (40.5%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: NR Exclusion criteria: 

NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) “Subjective” Morphology alone 

 Dis+ Dis- Tot T+ 21 6 27 

T- 3 143 146 Tot 24 149 173  Lower Upper  Value 95% CI 95% CI Se 87.5% 74.3% 100.0%Sp 96.0% 92.8% 99.1% PPV 77.8% 62.1% 93.5% NPV 97.9% 95.6% 100.0%

2) Morphology plus Doppler 

 Dis+ Dis- Tot T+ 20 5 25 T- 4 144 148 Tot 24 149 173  Lower Upper  Value 95% CI 95% CI Se 83.3% 68.4% 98.2% Sp 96.6% 93.8% 99.5% PPV 80.0% 64.3% 95.7% NPV 97.3% 94.7% 99.9% 

3) Lerner score 

 Dis+ Dis- Tot T+ 22 96 118 T- 2 53 55 Tot 24 149 173  Lower Upper  Value 95% CI 95% CI Se 91.7% 80.6% 100.0%Sp 35.6% 27.9% 43.3% PPV 18.6% 11.6% 25.7% NPV 96.4% 91.4% 100.0%

Quality ReferenVerificaTest reSample StatisticBlindingDefinitio + 
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

4) Time-averaged max velocity 

 Dis+ Dis- Tot T+ 24 61 85 

T- 0 59 59 Tot 24 120 144  Lower Upper  Value 95% CI 95% CI Se 100.0% 87.5% 100.0%Sp 49.2% 40.2% 58.1% PPV 28.2% 18.7% 37.8% NPV 100.0% 94.9% 100.0%

5) Morphology plus peak systolic velocity 

 Dis+ Dis- Tot T+ 19 44 63 T- 5 99 104 Tot 24 143 167  Lower Upper  Value 95% CI 95% CI Se 79.2% 62.9% 95.4% Sp 69.2% 61.7% 76.8% PPV 30.2% 18.8% 41.5% NPV 95.2% 91.1% 99.3% 

6) Morphology plus color score 

 Dis+ Dis- Tot T+ 17 39 56 T- 7 106 113 Tot 24 145 169  Lower Upper  Value 95% CI 95% CI Se 70.8% 52.6% 89.0% Sp 73.1% 65.9% 80.3% PPV 30.4% 18.3% 42.4% NPV 93.8% 89.4% 98.2% 

7) Morphology 
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

 Dis+ Dis- Tot T+ 23 94 117 T- 1 55 56 Tot 24 149 173  Lower Upper  Value 95% CI 95% CI Se 95.8% 87.8% 100.0%Sp 36.9% 29.2% 44.7% PPV 19.7% 12.5% 26.9% NPV 98.2% 94.7% 100.0%

8) Resistance index 

 Dis+ Dis- Tot T+ 6 7 13 T- 18 113 131 Tot 24 120 144  Lower Upper  Value 95% CI 95% CI Se 25.0% 7.7% 42.3% Sp 94.2% 90.0% 98.4% PPV 46.2% 19.1% 73.3% NPV 86.3% 80.4% 92.2% 

9) Pulsatility index 

 Dis+ Dis- Tot T+ 21 81 102 T- 3 39 42 Tot 24 120 144  Lower Upper  Value 95% CI 95% CI Se 87.5% 74.3% 100.0%Sp 32.5% 24.1% 40.9% PPV 20.6% 12.7% 28.4% NPV 92.9% 85.1% 100.0%
D-223

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommValentin, 2000 #2760 

Geographical location: Malmo, Sweden Dates: NR 

Size of population: 173 women Other Consecutive patients scheduled for surgery in university hospital Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Lerner’s ? PI and RI yes Valentin’s Doppler variable - no Statistical tests used: Se, Sp Blinding: NR – prospective though Definition of positive and negative on screening test: Lerner’s score [4] >3 RI < 0.4 PI < 1.0 

Age: Median: pre 37.5 for post 66 Range: 18-88 Menopausal status (n [%]): Pre: 98 (56.6%) Post: 70 (40.5%) 4 hysterectomy 1 unknown Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Women admitted to hospital for surgery due to pelvic mass during time frame Exclusion criteria: 26 excluded because 10 surgery canceled or replaced with cytology, 13 had normal US preop of whom 9 had normal laparoscopy and 4 had normal US followup 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Lerner score ≥ 3 

 Dis+ Dis- Tot T+ 22 53 75 

T- 2 96 98 Tot 24 149 173  Lower Upper  Value 95% CI 95% CI Se 91.7% 80.6% 100.0%Sp 64.4% 56.7% 72.1% PPV 29.3% 19.0% 39.6% NPV 98.0% 95.2% 100.0%

2) PI < 1.0 

 Dis+ Dis- Tot T+ 21 81 102 T- 3 68 71 Tot 24 149 173  Lower Upper  Value 95% CI 95% CI Se 87.5% 74.3% 100.0%Sp 45.6% 37.6% 53.6% PPV 20.6% 12.7% 28.4% NPV 95.8% 91.1% 100.0%

3) RI < 0.4 

 Dis+ Dis- Tot T+ 6 7 13 T- 18 142 160 Tot 24 149 173  Lower Upper  Value 95% CI 95% CI Se 25.0% 7.7% 42.3% Sp 95.3% 91.9% 98.7% PPV 46.2% 19.1% 73.3% NPV 88.8% 83.9% 93.6% 

Additional analyses for combination of Lerner score ≥3 and Doppler variable 

Comme--Undetclassifie--LMP tmaligna--LerneQuality ReferenVerificaTest reSample StatisticBlindingDefinitio+/- 
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

positive, combined as “both” or “either” = T+

Valentin, Hagen, Tingulstad, et al., 2001 #2340 

Geographical location: Trondheim, Norway, and Malmo, Sweden Dates: NR 

Size of population: 136 Other Prospective validation Reference standard: Surgery Reference standard applied to all test negatives?: Yes Test reliability established?: Referenced Statistical tests used: ROC, logistic regression Blinding: No Definition of positive and negative on screening test: “Pattern recognition” referenced, but not described in this paper 

Age: NR Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Scheduled for surgery for adnexal mass Exclusion criteria: Surgery cancelled No histology Death Multiple lesions in same ovary 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) “Pattern recognition” (threshold not defined, but referenced) 

 Dis+ Dis- Tot T+ 30 9 39 

T- 6 91 97 Tot 36 100 136  Lower Upper  Value 95% CI 95% CI Se 83.3% 71.2% 95.5% Sp 91.0% 85.4% 96.6% PPV 76.9% 63.7% 90.1% NPV 93.8% 89.0% 98.6% 

Comme--For C2x2 tabonly --For Uinto parreassemalone --Thresand 2 (VObstet 1999:14--ClinicaQuality ReferenVerificaTest reSample StatisticBlindingDefinitio + (not 
D-225

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Commvan Nagell Jr., DePriest, Reedy, et al., 2000 #2730 

Geographical location: USA Dates: 1987 - 1999 

Size of population: 14469 180with persistently abnormal screens leading to surgery Screening study Reference standard: Histopathology Reference standard applied to all test negatives?: No Normal screens were repeated in one year Abnormal screens were repeated in 4-6 weeks with morphology, CA-125 and Doppler Test reliability established?: yes Statistical tests used: Chi square Fisher’s exact test Kaplan Meier survival curve plotted Blinding: Prospective Definition of positive and negative on screening test: US – ovarian volume > 20cm3 for 

Age: Mean (SD): 54.7 (10.7) Range: 25-92 Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Age >=50 or age >=25 with documented family history of ovarian CA Exclusion criteria: NR 

Symptomatic (n [%]): 0 (0%) Detected by exam (n [%]): 0 (0%) Detected by imaging (n [%]): 180 (1.2%) Combination (n [%]): NR Additional data used for diagnosis: NR 

1) For the screened population as a whole 

 Dis+ 5 Tot T+ 17 163 180 

T- 4 14285 14289 Tot 21 14448 14469  Lower Upper  Value 95% CI 95% CI Se 81.0% 64.2% 97.7% Sp 98.9% 98.7% 99.0% PPV 9.4% 5.2% 13.7% NPV 100.0% 99.9% 100.0%

2) Adding the 4 (Table 6) who got CA > 12 months out 

 Dis+ 5 Tot T+ 17 163 180 T- 8 14281 14289 Tot 25 14444 14469  Lower Upper  Value 95% CI 95% CI Se 68.0% 49.7% 86.3% Sp 98.9% 98.7% 99.0% PPV 9.4% 5.2% 13.7% NPV 99.9% 99.9% 100.0%

Comme--4 patie12+ mowere inanalysis 12 mon--Bordebenign --TVUS Quality ReferenVerificaTest reSample StatisticBlindingDefinitio+/- 
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

premenopausal women, and > 10cm3 for postmenopausal women Or any cystic ovarian tumor with a solid or papillary projection into its lumen. For subsequent screening DePriest scoring system used with CA-125 and doppler 

Vasilev, Schlaerth, Campeau, et al., 1988 #6770 

Geographical location: Los Angeles, CA Dates: Mar 1984-Feb 

1986 Size of population: 182 women Other Nonconsecutive case series Reference standard: Surgery/pathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: NR Blinding: Yes Definition of positive 

Age: NR Menopausal status (n [%]): ≤ 50: 152 (83.1%) >50: 31 (17.0%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Preoperative diagnosis of pelvic mass Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) All patients CA-125 ≥ 35 U/ml 

 Dis+ Dis- Tot T+ 14 37 51 

T- 4 128 132 Tot 18 165 183  Lower Upper  Value 95% CI 95% CI Se 77.8% 58.6% 97.0% Sp 77.6% 71.2% 83.9% PPV 27.5% 15.2% 39.7% NPV 97.0% 94.0% 99.9% 

2) Age ≤ 50 

 Dis+ Dis- Tot T+ 6 35 41 

T- 0 111 111 Tot 6 146 152  Lower Upper  Value 95% CI 95% CI Se 100.0% 50.0% 100.0%Sp 76.0% 69.1% 83.0% PPV 14.6% 3.8% 25.5% NPV 100.0% 97.3% 100.0%

3) Age > 50 

Comme--Uncle“nonconpatients --Text ddata pro--BordeQuality ReferenVerificaTest reSample StatisticBlindingDefinitio + 
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

and negative on screening test: > 35 u/ML 

 Dis+ Dis- Tot T+ 8 2 10 

T- 4 17 21 Tot 12 19 31  Lower Upper  Value 95% CI 95% CI Se 66.7% 40.0% 93.3% Sp 89.5% 75.7% 100.0%PPV 80.0% 55.2% 100.0%NPV 81.0% 64.2% 97.7% 

Vuento, Pirhonen, Makinen, et al., 1995 #4070 

Geographical location: Turku, Finland Dates: NR 

Size of population: 1846 in initial pool; 1364 (74%) consented Screening studyReference standard: Cases reported to Finnish Cancer Registry over 2 1⁄2 year followup; true negative considered no cancer within 1 year Reference standard applied to all test negatives?: Yes Test reliability established?: Not referenced or described Statistical tests used: Chi-square 

Age: Mean (SD): 59 Range: 56-61 Menopausal status (n [%]): Post (> 55): 1364 (100%) Race/ethnicity (n [%]): NR Risk factors (n [%]): Family history: 376 (27.6%) Inclusion criteria: Presenting for mammography Exclusion criteria: NR 

Symptomatic (n [%]): 100% asymptomatic Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Combined US morphology and Doppler 

 Dis+ Dis- Tot T+ 1 159 160 

T- 0 1204 1204 Tot 1 1363 1364  Lower Upper  Value 95% CI 95% CI Se 100.0% 0.0% 100.0%Sp 88.3% 86.6% 90.0% PPV 0.6% 0.0% 1.8% NPV 100.0% 99.8% 100.0%

Positive case was borderline 2 cancers, 1 Stage 1A and 1 Stage III, within 2 years 2) Combined US morphology and Doppler, results of followup US in 160 women with abnormal screening ultrasound on first screen 

 Dis+ Dis- Tot T+ 1 27 28 T- 0 132 132 Tot 1 159 160  Lower Upper  Value 95% CI 95% CI Se 100.0% 0.0% 100.0%

Comme--Popul--Some but regalternatQuality ReferenVerificaTest reSample StatisticBlindingDefinitio + 
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

Blinding: Yes Definition of positive and negative on screening test: Negative: not visualized, volume less than 8 cc, uniformly hypoechogenic; PI < 1.0 – lowest measured value used US – Fleischer criteria 

Sp 83.0% 77.2% 88.9% PPV 3.6% 0.0% 10.4% NPV 100.0% 97.7% 100.0%

Wakahara, Kikkawa, Nawa, et al., 2001 #2370 

Geographical location: Nagoya, Japan Dates: 1994-1999 

Size of population: 292 women Other Case series Reference standard: Surgery/pathology Reference standard applied to all test negatives?: Yes Test reliability established?: Not referenced or discussed Statistical tests used: Se/Sp Blinding: Yes Definition of positive and negative on 

Age: Mean (SD): 40.3 Range: 11-79 Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Presence of adnexal mass, scheduled for surgery Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Ultrasound—Including borderline as cancer 

 Dis+ Dis- Tot T+ 69 37 106 

T- 15 171 186 Tot 84 208 292  Lower Upper  Value 95% CI 95% CI Se 82.1% 74.0% 90.3% Sp 82.2% 77.0% 87.4% PPV 65.1% 56.0% 74.2% NPV 91.9% 88.0% 95.8% 

2) Ultrasound—classifying borderline as benign 

 Dis+ Dis- Tot T+ 57 49 106 T- 9 177 186 Tot 66 226 292  Lower Upper  Value 95% CI 95% CI Se 86.4% 78.1% 94.6% Sp 78.3% 72.9% 83.7% PPV 53.8% 44.3% 63.3% NPV 95.2% 92.1% 98.2% 

3) CA-125 > 35 U/ml; borderline classified 

Comme--Clinica--Not stQuality ReferenVerificaTest reSample StatisticBlindingDefinitio + 
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

screening test: Positive ultrasound: cyst with irregular solid component or thickened septum, or solid mass. Ultrasound interpretation by gyn oncologist, not radiologist CA-125: 35 U/mL CA-19-9: 37 IU/mL CA-72-4: 4 U/mL 

as malignant 

 Dis+ Dis- Tot T+ 62 22 84 

T- 77 131 208 Tot 139 153 292  Lower Upper  Value 95% CI 95% CI Se 44.6% 36.3% 52.9% Sp 85.6% 80.1% 91.2% PPV 73.8% 64.4% 83.2% NPV 63.0% 56.4% 69.5% 

4) CA-125 > 35 U/ml; borderline classified as benign 

 Dis+ Dis- Tot T+ 51 88 139 T- 15 138 153 Tot 66 226 292  Lower Upper  Value 95% CI 95% CI Se 77.3% 67.2% 87.4% Sp 61.1% 54.7% 67.4% PPV 36.7% 28.7% 44.7% NPV 90.2% 85.5% 94.9% 

5) CA 19-9 > 37 IU/ml, borderline classified as malignant 

 Dis+ Dis- Tot T+ 29 78 107 T- 55 127 182 Tot 84 205 289  Lower Upper  Value 95% CI 95% CI Se 34.5% 24.4% 44.7% Sp 62.0% 55.3% 68.6% PPV 27.1% 18.7% 35.5% NPV 69.8% 63.1% 76.5% 

6) CA 19-9 >37 IU/ml, Borderline classified 
D-230

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

as benign 

 Dis+ Dis- Tot T+ 24 83 107 

T- 42 140 182 Tot 66 223 289  Lower Upper  Value 95% CI 95% CI Se 36.4% 24.8% 48.0% Sp 62.8% 56.4% 69.1% PPV 22.4% 14.5% 30.3% NPV 76.9% 70.8% 83.0% 

7) CA-72-4 > 4 U/ml, borderline classified as malignant 

 Dis+ Dis- Tot T+ 23 18 41 T- 28 104 132 Tot 51 122 173  Lower Upper  Value 95% CI 95% CI Se 45.1% 31.4% 58.8% Sp 85.2% 79.0% 91.5% PPV 56.1% 40.9% 71.3% NPV 78.8% 71.8% 85.8% 

8) CA-72-4 > 4 U/ml, borderline classified as benign 

 Dis+ Dis- Tot T+ 20 21 41 T- 20 116 136 Tot 40 137 177  Lower Upper  Value 95% CI 95% CI Se 50.0% 34.5% 65.5% Sp 84.7% 78.6% 90.7% PPV 48.8% 33.5% 64.1% NPV 85.3% 79.3% 91.2% 
D-231

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommWeiner, Thaler, Beck, et al., 1992 #6480 

Geographical location: Haifa, Israel Dates: NR 

Size of population: 62 women Other Prospective surgical candidates in single center Reference standard: Histopathology Reference standard applied to all test negatives?: No – 9 had “functional cysts” which had regressed on followup US Test reliability established?: CA-125 – yes PI +/- Statistical tests used: Se, Sp Blinding: NR – prospective study Definition of positive and negative on screening test: CA-125 > 35 U/ml PI < 1.0 US – {7} – not described 

Age: Range: 20-69 Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Women referred to US department for suspicion of pelvic tumor 62 referred – 9 with cysts that disappeared after 6 weeksExclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) CA-125 > 35 U/ml 

 Dis+ Dis- Tot T+ 14 14 28 

T- 3 22 25 Tot 17 36 53  Lower Upper  Value 95% CI 95% CI Se 82.4% 64.2% 100.0%Sp 61.1% 45.2% 77.0% PPV 50.0% 31.5% 68.5% NPV 88.0% 75.3% 100.0%

2) PI < 1.0 

 Dis+ Dis- Tot T+ 16 1 17 T- 1 35 36 Tot 17 36 53  Lower Upper  Value 95% CI 95% CI Se 94.1% 82.9% 100.0%Sp 97.2% 91.9% 100.0%PPV 94.1% 82.9% 100.0%NPV 97.2% 91.9% 100.0%

3) US 

 Dis+ Dis- Tot T+ 16 11 27 T- 1 25 26 Tot 17 36 53  Lower Upper  Value 95% CI 95% CI Se 94.1% 82.9% 100.0%Sp 69.4% 54.4% 84.5% PPV 59.3% 40.7% 77.8% NPV 96.2% 88.8% 100.0%

Comme--LMP ganalysis --Classfindings illumina--PPV fas 45% error) --Bordeare clastables Quality ReferenVerificaTest re+ for CA- for US Sample StatisticBlindingDefinitio+ for CA- for US 
D-232

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommWoolas, Conaway, Xu, et al., 1995 #4140 

Geographical location: Durham, NC, and London, UK Dates: NR 

Size of population: 429 Other Series from two hospitals Reference standard: Surgery, pathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: ROC, logistic modeling Blinding: Not described Definition of positive and negative on screening test: CA-125: 35 u/ML M-CSF: 3.1 ng/ml OVX 1: 12.1 U/mL LASA: 200.0 mg/ml CA 15-3: 32.0 u/ml CA-72-4: 3.8 u/ml CA 19-9: 39.0 u/ml CA 54/61: 20.0 u/ml 

Age: NR Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: NR Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): All patients with “clinically detected masses” Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: 148 primary ovarian cancers26% Stage I 3% Stage II 55% Stage III 16% Stage IV 

1) CA-125 > 35 U/ml 

 Dis+ Dis- Tot T+ 150 55 205 

T- 42 182 224 Tot 192 237 429  Lower Upper  Value 95% CI 95% CI Se 78.1% 72.3% 83.9% Sp 76.8% 71.4% 82.2% 

PPV 73.2% 67.1% 79.2% NPV 81.3% 76.1% 86.4% 

2) M-CSF 

 Dis+ Dis- Tot T+ 127 57 184 

T- 65 180 245 Tot 192 237 429  Lower Upper  Value 95% CI 95% CI Se 66.2% 59.5% 72.9% Sp 76.0% 70.6% 81.4% 

PPV 69.0% 62.3% 75.7% NPV 73.5% 67.9% 79.0% 

3) OVX1 

 Dis+ Dis- Tot T+ 77 41 118 

T- 115 196 311 Tot 192 237 429  Lower Upper  Value 95% CI 95% CI Se 40.1% 33.2% 47.0% Sp 82.7% 77.9% 87.5% 

PPV 65.3% 56.7% 73.8% NPV 63.0% 57.7% 68.4% 

4) LASA 

Comme--Clinica--Spectdistribu--Uncle(randomapproxi--Not stmenopa--Prevawould bpopulatQuality ReferenVerificaTest reSample StatisticBlindingDefinitio + 
D-233

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

 Dis+ Dis- Tot T+ 100 29 129 T- 92 208 300 Tot 192 237 429  Lower Upper  Value 95% CI 95% CI Se 52.1% 45.0% 59.2% Sp 87.8% 83.6% 92.0% 

PPV 77.5% 70.3% 84.7% NPV 69.3% 64.1% 74.6% 

5) CA 15-3 

 Dis+ Dis- Tot T+ 120 32 152 

T- 72 205 277 Tot 192 237 429  Lower Upper  Value 95% CI 95% CI Se 62.5% 55.7% 69.3% Sp 86.5% 82.1% 90.9% 

PPV 78.9% 72.5% 85.4% NPV 74.0% 68.8% 79.2% 

6) CA-72-4 

 Dis+ Dis- Tot T+ 104 20 124 

T- 88 217 305 Tot 192 237 429  Lower Upper  Value 95% CI 95% CI Se 54.2% 47.2% 61.2% Sp 91.6% 88.1% 95.1% 

PPV 83.9% 77.4% 90.3% NPV 71.1% 66.1% 76.2% 

7) CA 19-9 

 Dis+ Dis- Tot T+ 46 28 74 

T- 146 209 355
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

Tot 192 237 429  Lower Upper  Value 95% CI 95% CI Se 24.0% 18.0% 30.0% Sp 88.2% 84.1% 92.3% 

PPV 62.2% 51.1% 73.2% NPV 58.9% 53.8% 64.0% 

8) CA 54/61 

 Dis+ Dis- Tot T+ 100 28 128 

T- 92 209 301 Tot 192 237 429  Lower Upper  Value 95% CI 95% CI Se 52.1% 45.0% 59.2% Sp 88.2% 84.1% 92.3% 

PPV 78.1% 71.0% 85.3% NPV 69.4% 64.2% 74.6% 
D-235

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommWu, Lee, Chen, et al., 1994 #10900 

Geographical location: Taiwan Dates: Jul 1990 – Dec 

1993 Size of population: 410 Case series Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: Chi square Fisher exact Student t test Linear regression Blinding: Not mentioned (prospective) Definition of positive and negative on screening test: Positive: RI > 0.4 

Age: Range: 11-81 Menopausal status (n [%]): NR: Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Suspected malignancy on the basis of suspicious ultrasound Exclusion criteria: Patients examined during luteal phase 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) RI < 0.4 

 Dis+ Dis- Tot T+ 70 8 78 

T- 33 299 332 Tot 103 307 410  Lower Upper  Value 95% CI 95% CI Se 68.0% 59.0% 77.0% Sp 97.4% 95.6% 99.2% 

PPV 89.7% 83.0% 96.5% NPV 90.1% 86.8% 93.3% 

Comme--Clinica--CombUS (no to stratiQuality ReferenVerificaTest reSample StatisticBlindingDefinitio
D-236

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommYamashita, Hatanaka, Torashima, et al., 1997 #6120 

Geographical location: Japan Dates: NR 

Size of population: 104 women Other MRI series Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: No Statistical tests used: LR Blinding: Yes for MRI, independent interpretation by 3 radiologists - surgical and pathological reports were not available Definition of positive and negative on screening test: MRI evaluated for 1) size; 2) bilaterality; 3) wall structure; 4) internal architectures; 5) presence of thick (< 3 mm) septa; 6) signal intensity; 7) ascites 

Age: NR Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Ovarian masses and MRI to further investigate indeterminate ultrasound Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): 100% ultrasound Combination (n [%]): NR Additional data used for diagnosis: LR model Logit(y)=  -2.7 + 0.4 (tumor size) + 1.8 (ascites) + 1.4 (bilateral) + 0.5 (complex internal architecture) + 1.6 (solid or irregular wall structure) Where tumor size (cm), other variables scored 1if present; 0 if absent. Best discrimination obtained in test set with cutoff our 0.49. 

1) LR model (validation set) cutoff = 0.49 

 Dis+ Dis- Tot T+ 21 4 25 

T- 7 43 50 Tot 28 47 75  Lower Upper  Value 95% CI 95% CI Se 75.0% 59.0% 91.0% Sp 91.5% 83.5% 99.5% PPV 84.0% 69.6% 98.4% NPV 86.0% 76.4% 95.6% 

Comme--Low mmaligna--LR mopositive thumb) --2x2 tadoesn’t Sp. Outable. --ValidaQuality ReferenVerificaTest reSample StatisticBlindingDefinitiocutoff w
D-237

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommYamashita, Torashima, Hatanaka, et al., 1995 #4290 

Geographical location: Kumamoto, Japan Dates: NR 

Size of population: 72 women 80 masses Other Consecutive case series Reference standard: Surgery/pathology Reference standard applied to all test negatives?: Yes Test reliability established?: 

Inter-rater reliability measured Statistical tests used: ROC, kappa Blinding: Yes Definition of positive and negative on screening test: Benign if 3 of 4 criteria: • Diameter < 4 cm 

• Entirely cystic • Lesion wall < 3mm • No internal structure Malignancy if 2 of 5 criteria: • Diameter > 4 cm • Wall or septum > 

Age: Mean (SD): 43 Range: 13-74 Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR; presumably 100% Asian Risk factors (n [%]): NR

Inclusion criteria: Pelvic mass, scheduled for surgery Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Transvaginal ultrasound, benign vs malignant, all readings by 5 radiologists (results presented by lesion, not patient; 19 patients had malignancy, 61 benign lesions) 

 Dis+ Dis- Tot T+ 17 10 27 

T- 2 51 53 Tot 19 61 80  Lower Upper  Value 95% CI 95% CI Se 89.0% 74.9% 100.0%Sp 84.0% 74.8% 93.2% 

PPV 63.0% 44.7% 81.2% NPV 96.2% 91.1% 100.0%

2) Preconstrast MRI, benign vs malignant 

 Dis+ Dis- Tot T+ 15 4 19 

T- 4 57 61 Tot 19 61 80  Lower Upper  Value 95% CI 95% CI Se 78.0% 59.4% 96.6% Sp 93.0% 86.6% 99.4% 

PPV 78.9% 60.6% 97.3% NPV 93.4% 87.2% 99.7% 

3) Contrast-enhanced MRI, benign vs malignant 

 Dis+ Dis- Tot T+ 17 4 21 

T- 2 57 59 Tot 19 61 80  Lower Upper  Value 95% CI 95% CI Se 91.0% 78.1% 100.0%Sp 93.0% 86.6% 99.4% 

PPV 81.0% 64.2% 97.7% 

Comme--Obser Kappa 0.73 for 0.62 for --Se/Sp patient—--Not ststatus --ClinicaLMP tumalignaQuality ReferenVerificaTest reSample StatisticBlindingDefinitio + 
D-238

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

3mm 

• Nodularity, 

vegetations, or large solid component 

• Necrosis or 

hemorrhage in lesion 

And/or if any 1 of the following criteria: • Involvement of 

adjacent organs or pelvic sidewall 

• Peritoneal, 

mesenteric, or omental lesions 

• Ascites • Adenopathy Borderline tumors classified as malignant 

NPV 96.6% 92.0% 100.0%
D-239

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommZanetta, Vergani, and Lissoni, 1994 #10850 

Geographical location: Milan, Italy Dates: May 1992 – May 

1993 Size of population: 80 Case series Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Test reliability established?: Yes Statistical tests used: Se, Sp Blinding: Not mentioned (prospective) Definition of positive and negative on screening test: US morphology – Sassone’s criteria Doppler: PI>=1.0 RI range investigated (0.50, 0.56, 0.60) CA-125 >30U/ml 

Age: NR Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Surgical referral to hospital secondary to mass Exclusion criteria: NR 

Symptomatic (n [%]): 71(88.8%) Detected by exam (n [%]): NR Detected by imaging (n [%]): 5(6.3%) (infertility work up imaging) Combination (n [%]): NR Additional data used for diagnosis: 4 (5%) referred for abdominal enlargement but were asymptomatic 

1) US Sassone 

 Dis+ Dis- Tot T+ 32 11 43 

T- 1 36 37 Tot 33 47 80  Lower Upper  Value 95% CI 95% CI Se 97.0% 91.2% 100.0%Sp 76.0% 63.8% 88.2% 

PPV 74.4% 61.4% 87.5% NPV 97.3% 92.1% 100.0%

2) CA 126 > 30 

 Dis+ Dis- Tot T+ 30 19 49 

T- 3 28 31 Tot 33 47 80  Lower Upper  Value 95% CI 95% CI Se 91.0% 81.2% 100.0%Sp 60.0% 46.0% 74.0% 

PPV 61.2% 47.6% 74.9% NPV 90.3% 79.9% 100.0%

3) PI 1.0 

 Dis+ Dis- Tot T+ 32 6 38 

T- 1 41 42 Tot 33 47 80  Lower Upper  Value 95% CI 95% CI Se 97.0% 91.2% 100.0%Sp 87.0% 77.4% 96.6% 

PPV 84.2% 72.6% 95.8% NPV 97.6% 93.0% 100.0%

4) RI 0.60 

Comme--N = 80 cases t--Borde--Overlamaligna--TVUS Quality ReferenVerificaTest reSample StatisticBlindingDefinitio
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results Comm

 Dis+ Dis- Tot T+ 30 7 37 T- 3 40 43 Tot 33 47 80  Lower Upper  Value 95% CI 95% CI Se 91.0% 81.2% 100.0%Sp 85.0% 74.8% 95.2% 

PPV 81.1% 68.5% 93.7% NPV 93.0% 85.4% 100.0%

5) RI 0.56 

 Dis+ Dis- Tot T+ 28 4 32 

T- 5 43 48 Tot 33 47 80  Lower Upper  Value 95% CI 95% CI Se 85.0% 72.8% 97.2% Sp 91.0% 82.8% 99.2% 

PPV 87.5% 76.0% 99.0% NPV 89.6% 80.9% 98.2% 

6) RI 0.50 

 Dis+ Dis- Tot T+ 22 2 24 

T- 11 45 56 Tot 33 47 80  Lower Upper  Value 95% CI 95% CI Se 67.0% 51.0% 83.0% Sp 96.0% 90.4% 100.0%

PPV 91.7% 80.6% 100.0%NPV 80.4% 70.0% 90.8% 
D-241

Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommZhang, Barnhill, Zhang, et al., 1999 #3020 

Geographical location: London, England Dates: NR 

Size of population: 429 women Registry Reference standard: Pathology Reference standard applied to all test negatives?: Yes Test reliability established?: Statistical tests used: Se, Sp, ROC Blinding: 

NR

Definition of positive and negative on screening test: Artificial Neural Network (ANN), cutoff 0.5 Ca 125 > 35U/ml 

Age: NR Menopausal status (n [%]): NRRace/ethnicity (n [%]): NRRisk factors (n [%]): NR Inclusion criteria: Pelvic mass/had pathologyExclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

2) CA-125 > 35 U/ml 

 Dis+ Dis- Tot T+ 75 29 104 

T- 6 57 63 Tot 81 86 167  Lower Upper  Value 95% CI 95% CI Se 92.6% 86.9% 98.3% Sp 66.3% 56.3% 76.3% 

PPV 72.1% 63.5% 80.7% NPV 90.5% 83.2% 97.7% 

Comme--Traininon-epother cabenign couldn’the trainmalignaconditioapplicathe otheQuality ReferenVerificaTest reSample StatisticBlindingDefinitio
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Evidence Table 3 (continued) Study Study Design Patients Clinical Presentation Results CommZimmer, Tepper, and Akselrod, 2003 #1740 

Geographical location: Dates: 

NR Size of population: 28 images; number of patients not described Other Development of quantitative analytic method for ultrasound images; initial validation Reference standard: Presumably surgery/pathology Reference standard applied to all test negatives?: Yes Test reliability established?: Not described Statistical tests used: Not described Blinding: Yes Definition of positive and negative on screening test: Algorithm based on lesion size, structure, turbidity, amount of solid material 

Age: NR Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: NR Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Benign vs malignant, from 28 preoperative images 

 Dis+ Dis- Tot T+ 20 0 20 

T- 5 3 8 Tot 25 3 28  Lower Upper  Value 95% CI 95% CI Se 80.0% 64.3% 95.7% Sp 100.0% 0.0% 100.0%PPV 100.0% 85.0% 100.0%NPV 37.5% 4.0% 71.0% 

Comme--Clinica--SpectQuality ReferenVerificaTest reSample StatisticBlindingDefinitio + 
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Evidence Table 4: Question 4: What is the accuracy of explicit scoring systems which incorporate various combinations of imaging f

factors, and/or CA-125 levels for detecting malignancy? Have these scoring systems been applied to a population of women before lapaStudy Study Design Patients Clinical 

Presentation 

Items Included in Scoring System 

Results 

Adonakis, Paraskevaidis, Tsiga, et al., 1996 #810 

Geographical location: Ioannina, Greece Dates: Mar 1991-Jun 1993 Size of population: 2000 screened Screening study Reference standard: Histology or followup (at least 1 visit with CA-125 1 year later) Reference standard applied to all test negatives?: Yes Statistical tests used: Se, Sp, PPV Blinding: No Definition of positive and negative on screening test: See Scoring column 

Age: Mean: 58.1 Range: 45-80 Menopausal status (n [%]): Pre: 1302 Peri: 293 Post: 405 Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Age ≥ 45 years 

“without any evidence of adnexal pathology”Exclusion criteria: Prior history of ovarian cancer, any other malignancy, bilateral salpingooophorectomy or ascites 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): 59 115 with “ambiguous” exam Combination (n [%]): 

NR Additional data used for diagnosis: NR 

1) TVUS criteria for abnormal include any of the following: a) abnormal morphology – hyper- or hypo-echoic; b) irregular “outline;” c) volume > 18 ml for premenopausal and > 9 ml for postmenopausal women 2) CA-125 > 35 U/ml 

3) Pelvic examination abnormal when there is a palpable adnexal mass 

1) PE + CA-125 (“ambiguous” PE considered abnormal; no histological verification of test negatives) 

 Dis+ Dis- Tot T+ 3 177 180 

T- 0 1820 1820 Tot 3 1997 2000  Lower Upper  Value 95% CI 95% CI Se 100.0% 0.0% 100.0%Sp 91.1% 89.9% 92.4% PPV 1.7% 0.0% 3.5% NPV 100.0% 99.8% 100.0%

2) PE + CA-125 (“ambiguous” PE considered normal; no histological verification of 145 TVUS test negatives) 

 Dis+ Dis- Tot T+ 2 63 65 T- 1 114 115 Tot 3 177 180  Lower Upper  Value 95% CI 95% CI Se 66.7% 13.3% 100.0%Sp 64.4% 57.4% 71.5% PPV 3.1% 0.0% 7.3% NPV 99.1% 97.4% 100.0%

3) PE + CA-125 +TVUS (“ambiguous” PE considered normal; no histological verification of 145 TVUS test negatives) (see next page) 
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Evidence Table 4 (continued) Study Study Design Patients Clinical 

Presentation 

Items Included in Scoring System 

Results 

 Dis+ Dis- Tot T+ 3 68 71 

T- 0 109 109 Tot 3 177 180  Lower Upper  Value 95% CI 95% CI Se 100.0% 0.0% 100.0%Sp 61.6% 54.4% 68.7% PPV 4.2% 0.0% 8.9% NPV 100.0% 97.2% 100.0%
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Evidence Table 4 (continued) Study Study Design Patients Clinical 

Presentation 

Items Included in Scoring System 

Results 

Alcazar, Errasti, Zornoza, et al., 1999 #3110 

Geographical location: Pamplona, Spain Dates: Jan 1995-Feb 1998 Size of population: 94 women of 480 women screened Registry Retrospective singleinstitution series Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Statistical tests used: Se, Sp, ROC curves/AUC Blinding: No Definition of positive and negative on screening test: Yes 

Age: Mean: 47.4 Range: 17-79 Menopausal status (n [%]): Pre: 52 (55.3%) Post: 42 (44.7%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Diagnosed as having an adnexal mass andsonographically suspicious findings; transvaginal color Doppler and CA-125 level before surgery; and definitive histopathological diagnosis Exclusion criteria: 

NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): All 100% Combination (n [%]): NR Additional data used for diagnosis: Morphological evaluation including presence of at least one of: Multilocularity, gross septations (> 3 mm), gross papillary projections (> 3 mm), solid wall nodules, irregular borders, solid mass or ascites 

1) CA-125 ≥ 35 U/ml 2) RI ≤ 0.4 

1) Combination of RI ≤ 0.4 and CA125 ≥ 35 U/ml 

 Dis+ Dis- Tot T+ 42 1 43 

T- 14 37 51 Tot 56 38 94  Lower Upper  Value 95% CI 95% CI Se 75.0% 63.7% 86.3% Sp 97.4% 92.3% 100.0%PPV 97.7% 93.2% 100.0%NPV 72.5% 60.3% 84.8% 
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Evidence Table 4 (continued) Study Study Design Patients Clinical 

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Items Included in Scoring System 

Results 

Andersen, Knudsen, Rix, et al., 2003 #1810 

Geographical location: Northern Jutland, Denmark Dates: Jul 1999-Aug 2001 Size of population: 447 Registry Reference standard: Histology or repeat exam every 2-3 months Reference standard applied to all test negatives?: No; in 45 cases, patients did not have histology and were observed at 2- to 3- month intervals. No patients were lost to followup. Statistical tests used: Se, Sp Blinding: No Definition of positive and negative on screening test: Well defined, including cutoff value of 200 RMI2 = U x M x CA125 (Tingulstad, Hagen, Skjeldestad, et al., 1996 [#3890]) 

Age: Range: 30 or older Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: 30 years of age or older; pelvic mass identified in region Exclusion criteria: 

None 

Symptomatic (n [%]): NR Detected by exam (n [%]): NRDetected by imaging (n [%]): NR Combination (n [%]): All had palpable or US demonstrated pelvic mass Additional data used for diagnosis: Vaginal ultrasound Menopausal status CA-125 

1) CA-125 Absolute value of serum CA-125 (IMX, Abbott Labs) 2) Ultrasound score (U; transvaginal) based on presence of the following factors:  solid areas (1)  multilocularity (1)  bilaterality (1)  ascites (1)  extraovarian tumors (1) If total ≥ 2, then U = 4 

If total < 2, then U = 1 3) Menopausal score (M): Postmenopausal (> 1 year of amenorrhea) = 4 Premenopausal = 1 RMI2 = U x M x CA-125 (Tingulstad, Hagen, Skjeldestad, et al., 1996 [#3890]) 

1) RMI2 (among all patients; 45 of whom had clinical followup in lieu of histopathological diagnosis) Test + = RMI2 ≥ 200 

Test - = RMI2 < 200 

 Dis+ Dis- Tot T+ 72 37 109 

T- 30 308 338 Tot 102 345 447  Lower Upper  Value 95% CI 95% CI Se 70.6% 61.7% 79.4% Sp 89.3% 86.0% 92.5% PPV 66.1% 57.2% 74.9% NPV 91.1% 88.1% 94.2% 

2) RMI2 data limited only to surgically treated patients (all verified with histopathology) 

 Dis+ Dis- Tot T+ 72 37 109 T- 30 263 293 Tot 102 300 402  Lower Upper  Value 95% CI 95% CI Se 70.6% 61.7% 79.4% Sp 87.7% 83.9% 91.4% PPV 66.1% 57.2% 74.9% NPV 89.8% 86.3% 93.2% 

Results were reported, but have not been abstracted, for the following: Analysis that considered Stage 1 ovarian cancer as a “benign” disease resulting in Se 95.5% (63/66) and Sp 87.9% (335/381) 
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Evidence Table 4 (continued) Study Study Design Patients Clinical 

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Results 

Andolf, Jorgensen, and Astedt, 1990 #1200 

Geographical location: Lund, Sweden Dates: Oct 1984-Jul 1987 Size of population: 801 women Screening study Registry Reference standard: Histopathology Reference standard applied to all test negatives?: No, women without abnormality or cysts < 20 mm diameter considered normal and not verified. Ascertainment of ovarian cancer in test negative relies on Sweden’s public health cancer registry system, which is well validated. Statistical tests used: Se, Sp Blinding: NoneDefinition of positive and negative on screening test: NR 

Age: Range: 40-70 Menopausal status (n [%]): Pre (< 45): 330 (41%) Peri (45-55): 212 (26%) Post (> 55): 259 (32%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Women between 40-70 years of age in one of 4 groups: 1) abdominal pain, frequent micturition or irregular bleeding; 2) nulliparity; 3) family history of breast, endometrial or ovarian cancer; 4) previous history of cancer Exclusion criteria: 

NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): 106 total51 (7.9%) of women with normal US 55 women with abnormal US Detected by imaging (n [%]): 163 women total 108 women with normal manual exam 55 women with abnormal manual examCombination (n [%]): 55 women with abnormal exam and USAdditional data used for diagnosis: None 

1) Bimanual PE 2) Abdominal US 

1) Either US or PE abnormal 

 Dis+ Dis- Tot T+ 8 206 214 

T- 0 587 587 Tot 8 793 801  Lower Upper  Value 95% CI 95% CI Se 100.0% 62.5% 100.0%Sp 74.0% 71.0% 77.1% PPV 3.7% 1.2% 6.3% NPV 100.0% 99.5% 100.0%

2) Both US and PE abnormal 

 Dis+ Dis- Tot T+ 5 50 55 T- 3 743 746 Tot 8 793 801  Lower Upper  Value 95% CI 95% CI Se 62.5% 29.0% 96.0% Sp 93.7% 92.0% 95.4% PPV 9.1% 1.5% 16.7% NPV 99.6% 99.1% 100.0%
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Evidence Table 4 (continued) Study Study Design Patients Clinical 

Presentation 

Items Included in Scoring System 

Results 

Asif, Sattar, Dawood, et al., 2004 #1580 

Geographical location: Rawalpindi, Pakistan Dates: Jan 2001 to Jan 2002 Size of population: 100 women Surgical case series Reference standard: Histopathological diagnosis Reference standard applied to all test negatives?: Yes Statistical tests used: Se, Sp, PPV, NPV Blinding: None Definition of positive and negative on screening test: Implicitly defined by use of Jacobs instrument (Jacobs, Oram, Fairbanks, et al., 1990 [#6820]), but analysis considered multiple cutoff values 

Age: Mean (SD): 41.4 Menopausal status (n [%]): Pre (< 45): 56 (56%)Post (> 55): 44 (44%) ≥ 1 year amenorrhea Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Consecutive women admitted to one of 2 military hospitals for elective surgical exploration and resection of proven ovarian mass Exclusion criteria: 

None 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) CA-125 Absolute value of serum CA-125 by solid phase two-site chemiluminescent enzyme immunometric assay using Immulite CA-125 kit (DPC, USA) 2) Ultrasound score (U; transvaginal) based on presence of the following factors:  solid areas (1)  multilocularity (1)  bilaterality (1)  ascites (1)  extraovarian tumors (1) If total is 0, then U = 0 If total is 1, then U = 1 If total ≥ 2, then U = 3 

3) Menopausal score (M): Postmenopausal (> 1 year of amenorrhea) = 3 Premenopausal = 1 RMI1 = U x M x CA-125 (Jacobs, Oram, Fairbanks, et al., 1990 [#6820]) 

1) RMI1 with cutoff value of 200 

 Dis+ Dis- Tot T+ 47 3 50 

T- 8 42 50 Tot 55 45 100  Lower Upper  Value 95% CI 95% CI Se 85.0% 75.6% 94.4% Sp 93.0% 85.5% 100.0%PPV 94.0% 87.4% 100.0%NPV 84.0% 73.8% 94.2% 

2) RMI1 with cutoff value of 125 

 Dis+ Dis- Tot T+ 48 5 53 T- 7 40 47 Tot 55 45 100  Lower Upper  Value 95% CI 95% CI Se 87.0% 78.1% 95.9% Sp 88.0% 78.5% 97.5% PPV 90.6% 82.7% 98.4% NPV 85.1% 74.9% 95.3% 

Results were reported, but have not been abstracted, for the following combinations: RMI1 with cutoff levels of 25, 50, 75, 100, 150, 175, 190, 250, 300 
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Evidence Table 4 (continued) Study Study Design Patients Clinical 

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Items Included in Scoring System 

Results 

Aslam, Banerjee, Carr, et al., 2000 #2690 

Geographical location: South London, UK Dates: NR Size of population: 100 women RegistryReference standard: Histopathological diagnosis from laparotomy Reference standard applied to all test negatives?: Yes Statistical tests used: Se, Sp, ROC curves/AUC Blinding: No Definition of positive and negative on screening test: NA 

Age: Mean: 45.6 Range: 20-78 Menopausal status (n [%]): Pre: 63 (63%) Post: 37 (37%) ≥ 1 year amenorrhea or age > 50 if status post hysterectomy Race/ethnicity (n [%]): NRRisk factors (n [%]): NR Inclusion criteria: Women with known adnexal masses and due to undergo surgery at one of 3 UK hospitals Exclusion criteria: 

None 

Symptomatic (n [%]): NR Detected by exam (n [%]): NRDetected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Tailor model LR1 uses age, TAMXV (Doppler), papillary projection score (US): 

P = 1/(1 + e - z), where z = 0.1273 x age + 0.2794 x TAMXV + 4.4136 x PPS - 14.2046 Cutoff = 50% 2) Timmerman model LR3 uses CA-125, morphologic and demographic data. Z = 0.5948 x menopausal status + 0.0205 x CA-125 + 0.5446 x ascites - 0.762 x unilocularity 1.1606 x smooth + 1.5409 x PPS + 0.7633 x bilateral - 1.0889 P > 50% assumed to be diagnostic of malignancy 3) LR1 + LR2 4) LR1 + LR3 5) LR1 + LR2 + LR3 Where LR2 = Alcazar (1998) model using morphologic features with Doppler blood flow variables Ascites = 1 or 0 

1) Tailor model LR1 

 Dis+ Dis- Tot T+ 15 5 20 

T- 18 62 80 Tot 33 67 100  Lower Upper  Value 95% CI 95% CI Se 45.0% 28.0% 62.0% Sp 93.0% 86.9% 99.1% PPV 75.0% 56.0% 94.0% NPV 77.5% 68.3% 86.7% 

AUC 0.86 (0.77 to 0.94) 2) Timmerman model LR3 

 Dis+ Dis- Tot T+ 24 6 30 T- 9 61 70 Tot 33 67 100  Lower Upper  Value 95% CI 95% CI Se 73.0% 57.9% 88.1% Sp 91.0% 84.1% 97.9% PPV 80.0% 65.7% 94.3% NPV 87.1% 79.3% 95.0% 

AUC 0.93 (0.89 to 0.98) 3) LR1+LR2 

 Dis+ Dis- Tot T+ 20 5 25 T- 13 62 75 Tot 33 67 100  Lower Upper  Value 95% CI 95% CI Se 61.0% 44.4% 77.6% Sp 93.0% 86.9% 99.1% PPV 80.0% 64.3% 95.7% NPV 82.7% 74.1% 91.2% 

AUC 0.85 
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Evidence Table 4 (continued) Study Study Design Patients Clinical 

Presentation 

Items Included in Scoring System 

Results 4) LR1 + LR3 

 Dis+ Dis- Tot T+ 26 4 30 

T- 7 63 70 Tot 33 67 100  Lower Upper  Value 95% CI 95% CI Se 79.0% 65.1% 92.9% Sp 94.0% 88.3% 99.7% PPV 86.7% 74.5% 98.8% NPV 90.0% 83.0% 97.0% 

AUC 0.95 5) LR2 + LR3 

 Dis+ Dis- Tot T+ 24 11 35 T- 9 56 65 Tot 33 67 100  Lower Upper  Value 95% CI 95% CI Se 73.0% 57.9% 88.1% Sp 84.0% 75.2% 92.8% PPV 68.6% 53.2% 84.0% NPV 86.2% 77.8% 94.6% 

AUC 0.88 
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Evidence Table 4 (continued) Study Study Design Patients Clinical 

Presentation 

Items Included in Scoring System 

Results 

Aslam, Tailor, Lawton, et al., 2000 #2580 

Geographical location: South London, UK Dates: Jul 1997-Sep 1998 Size of population: 61 women Diagnostic test study Reference standard: Histopathological diagnosis Reference standard applied to all test negatives?: Yes Statistical tests used: Se, Sp Blinding: None Definition of positive and negative on screening test: As defined by models used 

Age: Mean: 46.8 Range: 20-77 Menopausal status (n [%]): Pre (< 45): 36 Post (> 55): 25 ≥ 1 year amenorrhea or age > 50 if status post hysterectomy Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Women with known adnexal masses due to be admitted for surgery Exclusion criteria: 

None 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) RMI1 – Jacobs, Oram, Fairbanks, et al., 1990 (#6820)RMI1 = ultrasound score (U; 0, 1, 3) x menopausal status (M; 1, 3) x serum CA-125 RMI1 > 200 indicates malignancy 1 point each for: Bilateral lesions Multilocular Ascites Solid areas Intraabdominal metastases 

U = 0 if total is 0 1 if total is 1 and 3 if total is ≥ 2 M: Premenopausal = 1 Postmenopausal = 3 CA-125 in kU/L 2) RMI2 – Tingulstad, Hagen, Skjeldestad, et al., 1996 (#3890) As RMI1 except U = 1 if total is 0 or 1 4 if total ≥ 2; M = 1 or 4 

in this model 3) Tailor model [Ref # 17] LR1 uses age, TAMXV (Doppler), PPS (US): P = 1/(1 + e - z), where z = 0.1273 x age + 0.2794 x TAMXV + 4.4136 x PPS - 14.2046 

1) RMI1 with cutoff value of 200 

 Dis+ Dis- Tot T+ 17 3 20 

T- 6 35 41 Tot 23 38 61  Lower Upper  Value 95% CI 95% CI Se 73.9% 56.0% 91.9% Sp 92.1% 83.5% 100.0%PPV 85.0% 69.4% 100.0%NPV 85.4% 74.5% 96.2% 

2) RMI2 with cutoff value of 200 

 Dis+ Dis- Tot T+ 17 4 21 T- 6 34 40 Tot 23 38 61  Lower Upper  Value 95% CI 95% CI Se 73.9% 56.0% 91.9% Sp 89.5% 79.7% 99.2% PPV 81.0% 64.2% 97.7% NPV 85.0% 73.9% 96.1% 

3) Tailor’s model with cutoff value of 50% 

 Dis+ Dis- Tot T+ 10 3 13 T- 13 35 48 Tot 23 38 61  Lower Upper  Value 95% CI 95% CI Se 43.5% 23.2% 63.7% Sp 92.1% 83.5% 100.0%PPV 76.9% 54.0% 99.8% NPV 72.9% 60.3% 85.5% 
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Evidence Table 4 (continued) Study Study Design Patients Clinical 

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Items Included in Scoring System 

Results 

Balbi, Musone, Menditto, et al., 2001 #2320 

Geographical location: Naples, Italy Dates: Jan 1996-Mar 2000 Size of population: 92 women Case series Reference standard: Histopathological diagnosis Reference standard applied to all test negatives?: No, 18 women with “clearly benign” masses not verified; 2 patients with “clearly malignant” disease (metastases) also excluded Statistical tests used: Se, Sp Blinding: None Definition of positive and negative on screening test: Defined 

Age: Range: 40-80 Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Women evaluated for pelvic mass at one institution Exclusion criteria: 

None 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: None 

1) Logistic regression fitted model: Z = -5.39224 + 2.35132 x US + 2.81806 x PE + 1.58268 x CA-125 + 0.607183 x CA-72-4 -1.11594 x RI Each variable is “suspicious” (1) or “not suspicious” (0) 2) TVUS (with transabdominal imaging if large tumor) Interpreted according to Valentin et al.: unilocular (1); 

multilocular (2); unilocular solid cyst (3); multilocular solid cyst (4); solid tumor (5) 3) PE physical exam by standard protocol. Examiner was asked to guess benign or malignant. This clinical impression was used in model. No mention of blinding to other data. 4) CA-125 levels > 35 U/ml considered abnormal 5) CA-72-4 levels > 3 U/ml considered abnormal 6) Intratumoral resistance index (RI) was evaluated by color Doppler. RI < 0.4 

1) Logistic regression model prediction

 Dis+ Dis- Tot T+ 17 5 22 

T- 5 45 50 Tot 22 50 72  Lower Upper  Value 95% CI 95% CI Se 77.3% 59.8% 94.8% Sp 90.0% 81.7% 98.3% PPV 77.3% 59.8% 94.8% NPV 90.0% 81.7% 98.3% 

Results were reported, but have not been abstracted, for the following combinations: Se and Sp were given for individual components (PE, US, CA-125, CA-72-4) as well as various combinations (not clearly defined how these were operationalized – but apparently not with fitted LR models) 
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Evidence Table 4 (continued) Study Study Design Patients Clinical 

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Items Included in Scoring System 

Results 

considered abnormal. 

Biagiotti, Desii, Vanzi, et al., 1999 #2990 

Geographical location: Florence, Italy Dates: NR Size of population: 207 women (226 adnexal masses) Case series; diagnostic test study Reference standard: Histopathological diagnosis Reference standard applied to all test negatives?: Yes Statistical tests used: Se, Sp Blinding: None Definition of positive and negative on screening test: Determined by model fit 

Age: Range: 21-74 Menopausal status (n [%]): Pre (< 45): 146 (70.5%) Post (> 55): 61 (29.5%) Race/ethnicity (n [%]): NR Risk factors (n [%]): 19 patients had bilateral adnexal masses Inclusion criteria: Women undergoing TVUS before surgery for adnexal masses Exclusion criteria: 

None 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Logistic regression models built from five training subsets of the data; candidate variables included: age, and 6 US variables: mean diameter of mass (mm), multilocularity, papillary projections, random echogenicity, peak systolic velocity (cm/sec), RI 2) Artificial neural network using the 5 predictor variables identified from forward stepwise selection in LR training set models: age, and 6 US variables: papillary projections, random echogenicity, peak systolic velocity (cm/sec), RI 3) TVUS with transabdominal US for large masses. Color Doppler imaging used to calculate RI. 

1) Logistic regression models T+ indicates > 50% probability of malignancy. Analysis based on number of tumors rather than number of patients. 

 Dis+ Dis- Tot T+ 43 6 49 

T- 8 169 177 Tot 51 175 226  Lower Upper  Value 95% CI 95% CI Se 84.3% 74.3% 94.3% Sp 96.6% 93.9% 99.3% PPV 87.8% 78.6% 96.9% NPV 95.5% 92.4% 98.5% 

2) Artificial neural networks Analysis based on number of tumors rather than number of patients. Cutoff > 50%. 

 Dis+ Dis- Tot T+ 49 4 53 T- 2 171 173 Tot 51 175 226  Lower Upper  Value 95% CI 95% CI Se 96.1% 90.8% 100.0%Sp 97.7% 95.5% 99.9% PPV 92.5% 85.3% 99.6% NPV 98.8% 97.3% 100.0%
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Evidence Table 4 (continued) Study Study Design Patients Clinical 

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Results 

Chou, Chang, Yao, et al., 1994 #10930 

Geographical location: Tainan, Taiwan Dates: Jan 1991-Feb 1993 Size of population: 108 women Registry Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Statistical tests used: Se, Sp, PPV, NPV Blinding: None Definition of positive and negative on screening test: See under “Scoring System.” Neither TVUS morphology criteria nor color Doppler US intratumoral vessel criteria were explicitly defined/described. 

Age: Mean: 38 Range: 11-85 Menopausal status (n [%]): Pre (< 45): 84 (78%)Post (> 55): 19 (18%) Premenarchal: 5 (4%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Women undergoing surgery for adnexal tumors Exclusion criteria: 

NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): 108 (100%) by CT or US Combination (n [%]): NR Additional data used for diagnosis: NR 

1) TVUS - morphology 2) Color Doppler US to visualize intratumoral vessel and flow velocity 3) RI with cutpoint of 0.5 4) Serum CA-125 level with cutpoint of 35 U/ml  or 65 U/ml 

1) RI < 0.5 or CA-125 > 35 U/ml 

 Dis+ Dis- Tot T+ 25 2 27 

T- 0 81 81 Tot 25 83 108  Lower Upper  Value 95% CI 95% CI Se 100.0% 88.0% 100.0%Sp 97.0% 93.3% 100.0%PPV 92.6% 82.7% 100.0%NPV 100.0% 96.3% 100.0%

2) RI < 0.5 or CA-125 > 65 U/ml 

 Dis+ Dis- Tot T+ 25 0 25 T- 0 83 83 Tot 25 83 108  Lower Upper  Value 95% CI 95% CI Se 100.0% 88.0% 100.0%Sp 100.0% 96.4% 100.0%PPV 100.0% 88.0% 100.0%NPV 100.0% 96.4% 100.0%
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Davies, Jacobs, Woolas, et al., 1993 #4720 

Geographical location: London, UK Dates: NR Size of population: 124 women Retrospective series Reference standard: Histopathological or operative report diagnosis Reference standard applied to all test negatives?: Yes Statistical tests used: Se, Sp, ROC curves Blinding: None Definition of positive and negative on screening test: Multiple cutoffs tested; measures defined as per Jacobs, Oram, Fairbanks, et al., 1990 (#6820) 

Age: NR Menopausal status (n [%]): Pre: 86 (69%) Post: 38 (31%) ≥ 1 year amenorrhea or age > 50 if status post hysterectomy Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Consecutive admissions for surgical exploration of adnexal mass Exclusion criteria: 

None 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) RMI1 of Jacobs, Oram, Fairbanks, et al., 1990 (#6820) RMI = U x M x CA-125 2) Menopausal status (M) scored as follows: Postmenopausal (> 1 year of amenorrhea) = 3 Premenopausal =1 3) Serum CA-125 level by RIA kit (CIS Bioindustries, France). Scored as absolute value. 4) Pelvic US score (U; transabdominal) based on presence of the 

following factors:  multilocularity (1)  solid areas (1)  bilaterality (1)  ascites (1)  extraovarian tumors (1) If total is 0, then U = 0 If total is 1, then U = 1 If total ≥ 2, then U = 3 

1) RMI1 (Jacobs, Oram, Fairbanks, et al., 1990 [#6820]) with cutoff value of 200 for T+ 

 Dis+ Dis- Tot T+ 33 11 44 

T- 4 76 80 Tot 37 87 124  Lower Upper  Value 95% CI 95% CI Se 89.0% 78.9% 99.1% Sp 87.0% 79.9% 94.1% PPV 75.0% 62.2% 87.8% NPV 95.0% 90.2% 99.8% 

Results were reported, but have not been abstracted, for the following combinations: CA-125 with cutoff values of 30, 50, 70, 90, 120 Ultrasound score with cutoff values of 1 and 3 Menopausal status (post vs pre) RMI with cutoffs of 25, 50, 75, 100, 150, 250 
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Dowd, Quinn, Rome, et al., 1993 #4680 

Geographical location: Melbourne, Australia Dates: NR Size of population: 264 women Registry Reference standard: Histopathology Reference standard applied to all test negatives?: Yes

Statistical tests used: Se, SpBlinding: 

None

Definition of positive and negative on screening test: RMI > 200 

Age: Mean: 50.2 Range: 15-89 Menopausal status (n [%]): Pre: 121 (46%) Post: 143 (54%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Serum CA-125 performed for evaluation of pelvic mass Exclusion criteria: No suspected pelvic mass; CA-125 obtained for screening only; no histopathology 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): 

NR Additional data used for diagnosis: CA-125 Menopausal status Ultrasound score 

1) CA-125 Absolute value (capped at 500) 2) Ultrasound score (U); criteria not described (0, 1, or 3 depending on the presence of particular features) 3) Menopausal score 

(M) Postmenopausal (> 1 year amenorrhea) = 3 Premenopausal = 1 RMI1 = U x M x CA-125 (Jacobs, Oram, Fairbanks, et al., 1990 [#6820]); cutoff > 2000 

1) RMI1 (n = 180 patients) Se = 70% Sp = 94% Can’t calculate 2x2 (marginals not reported for this 180-patient subset for whom RMI1 was available). No stratification by age or menopausal status. 
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Gadducci, Capriello, Bartolini, et al., 1988 #6650 

Geographical location: Pisa, Italy Dates: NR Size of population: 119 patients Diagnostic test study among referral series Reference standard: Histopathology; specimen obtained at laparotomy Reference standard applied to all test negatives?: Yes Statistical tests used: Se, Sp Blinding: No Definition of positive and negative on screening test: NA 

Age: NR Menopausal status (n [%]): NR Race/ethnicity (n [%]): NRRisk factors (n [%]): NR Inclusion criteria: Undergoing laparotomy for adnexal mass Exclusion criteria: 

None 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) US score based on: Shape (rounded-0 patients; polycyclic – 2 patients; poorly defined – 4 patients) Ascites (absent – 0 patients; present – 4 patients); Outline (regular – 0 patients; poorly defined – 2 patients; thickened – 4 patients) Structure (anechoic or mildly echogenic – 0 patients; homogeneous 

echogenic – 1 patient; multilocular – 2 patients; anechoic with echogenic areas – 3 patients; echogenic with anechoic areas – 4 patients) Total score determined by summing points for each parameter (range 0-16 patients) T- < 10 T+ ≥ 10 2) CA-125 solid phase sandwich radioimmunoassay (Centodor kit) T+ ≥ 65 U/ml T- < 65 U/ml 

1) Combined evaluation of US and CA-125 assay: T+ if either (or both) abnormal; T- if both normal 

 Dis+ Dis- Tot T+ 33 5 38 

T- 2 78 80 Tot 35 83 118  Lower Upper  Value 95% CI 95% CI Se 94.3% 86.6% 100.0%Sp 94.0% 88.9% 99.1% PPV 86.8% 76.1% 97.6% NPV 97.5% 94.1% 100.0%
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Guerriero, Ajossa, Risalvato, et al., 1998 #3400 

Geographical location: Cagliari, Italy Dates: Jan 1996-May 1997 Size of population: 192 adnexal masses in 178 women from among 240 eligible referred women Registry Consecutive Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Statistical tests used: Se, Sp Blinding: NR Definition of positive and negative on screening test: Yes 

Age: Mean (SD): 41 (15) Range: 14-77 Menopausal status (n [%]): Pre: 127 (71%) Post: 51 (29%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Consecutive women with adnexal mass based on palpation or sonography Exclusion criteria: 

Pregnant 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) B-mode TVUS; Morphological criteria defined for benign disorders 2) Color Doppler imaging with PI and RI calculated. If no Doppler waveforms were obtained, then the result was considered negative. 3) CA-125 (> 35 U/ml or > 65 U/ml) 

1) CDE and CA-125 ≥ 65 U/ml (all 

patients – numbers are masses) 

 Dis+ Dis- Tot T+ 22 5 27 

T- 11 140 151 Tot 33 145 178  Lower Upper  Value 95% CI 95% CI Se 66.7% 50.6% 82.8% Sp 96.6% 93.6% 99.5% PPV 81.5% 66.8% 96.1% NPV 92.7% 88.6% 96.9% 

2) CDE and CA-125 ≥ 65 U/ml 

(postmenopausal women only – numbers are masses) 

 Dis+ Dis- Tot T+ 17 0 17 

T- 9 27 36 Tot 26 27 53  Lower Upper  Value 95% CI 95% CI Se 65.4% 47.1% 83.7% Sp 100.0% 88.9% 100.0%PPV 100.0% 82.4% 100.0%NPV 75.0% 60.9% 89.1% 

3) CDE and CA-125 ≥ 65 U/ml 

(premenopausal women only – numbers are masses) 

 Dis+ Dis- Tot T+ 5 5 10 

T- 2 113 115 Tot 7 118 125  Lower Upper  Value 95% CI 95% CI Se 71.4% 38.0% 100.0%Sp 95.8% 92.1% 99.4% 
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PPV 50.0% 19.0% 81.0% 

4) CDE and CA-125 ≥ 35 U/ml 

(postmenopausal women only – numbers are masses) 

 Dis+ Dis- Tot T+ 21 1 22 

T- 5 26 31 Tot 26 27 53  Lower Upper  Value 95% CI 95% CI Se 80.8% 65.6% 95.9% Sp 96.3% 89.2% 100.0%PPV 95.5% 86.8% 100.0%NPV 83.9% 70.9% 96.8% 

5) B-mode and CA-125 ≥ 65 U/ml (postmenopausal women only – numbers are masses) 

 Dis+ Dis- Tot T+ 17 0 17 T- 9 27 36 Tot 26 27 53  Lower Upper  Value 95% CI 95% CI Se 65.4% 47.1% 83.7% Sp 100.0% 88.9% 100.0%PPV 100.0% 82.4% 100.0%NPV 75.0% 60.9% 89.1% 

6) B-mode and CA-125 ≥ 35 U/ml (postmenopausal women only – numbers are masses) 

 Dis+ Dis- Tot T+ 21 1 22 T- 5 26 31 Tot 26 27 53  Lower Upper 
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 Value 95% CI 95% CI Se 80.8% 65.6% 95.9% Sp 96.3% 89.2% 100.0%PPV 95.5% 86.8% 100.0%NPV 83.9% 70.9% 96.8% 
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Guerriero, Alcazar, Coccia, et al., 2002 #2130 

Geographical location: Cagliari, Florence, and Navarra, Italy Dates: Apr 1997-Jul 2000 Size of population: 826 masses in 789 women from a potential study population of 1020 women Registry Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Statistical tests used: Se, Sp, PPV, NPV Blinding: None Definition of positive and negative on screening test: Yes 

Age: Mean (SD): 40 (14) Range: 14-81 Menopausal status (n [%]): Pre: 617 (78%) Post: 172 (22%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: All women scheduled for surgery for the presence of a persistent adnexal mass Exclusion criteria: 

Anechoic unilocular or bilocular cystic mass with a thin regular wall without endocystic vegetation (n = 234) 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) US morphology 2) Color Doppler US 3) CA-125 

1) B-mode and CA-125 > 35 U/ml (postmenopausal women only – numbers are masses) 

 Dis+ Dis- Tot T+ 73 6 79 

T- 20 74 94 Tot 93 80 173  Lower Upper  Value 95% CI 95% CI Se 78.5% 70.1% 86.8% Sp 92.5% 86.7% 98.3% PPV 92.4% 86.6% 98.2% NPV 78.7% 70.4% 87.0% 

2) Color Doppler and CA-125 > 35 U/ml (postmenopausal women only – numbers are masses) 

 Dis+ Dis- Tot T+ 71 3 74 T- 22 76 98 Tot 93 79 172  Lower Upper  Value 95% CI 95% CI Se 76.3% 67.7% 85.0% Sp 96.2% 92.0% 100.0%PPV 95.9% 91.5% 100.0%NPV 77.6% 69.3% 85.8% 

3) B-mode and CA-125 > 35 U/ml (all women – numbers are masses) 

 Dis+ Dis- Tot T+ 113 30 143 T- 34 649 683 Tot 147 679 826  Lower Upper  Value 95% CI 95% CI Se 76.9% 70.1% 83.7% Sp 95.6% 94.0% 97.1% 
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PPV 79.0% 72.3% 85.7% NPV 95.0% 93.4% 96.7% 

4) Color Doppler and CA-125 > 35 U/ml (all women – numbers are masses) 

 Dis+ Dis- Tot T+ 112 10 122 

T- 35 669 704 Tot 147 679 826  Lower Upper  Value 95% CI 95% CI Se 76.2% 69.3% 83.1% Sp 98.5% 97.6% 99.4% PPV 91.8% 86.9% 96.7% NPV 95.0% 93.4% 96.6% 
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Jacobs, Oram, Fairbanks, et al., 1990 #6820 

Geographical location: London, UK Dates: NR Size of population: 143 women Unclear whether retrospective or prospective series; diagnostic test study Reference standard: Histopathological or operative report diagnosis Reference standard applied to all test negatives?: No Statistical tests used: Se, Sp, ROC curves, LR Blinding: Clinical assessment blind only to CA-125 level Definition of positive and negative on screening test: No a priori cutoff 

Age: Mean: 51.8 Menopausal status (n [%]): Pre: 61 Post: 82 > 1 year of amenorrhea or age > 50 if status post hysterectomy Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Admitted for elective surgical investigation of an adnexal mass Exclusion criteria: 

None 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

RMI1 – clinical prediction rule developed from logistic regression model based on ultrasound, CA-125 and menopausal status RMI1 = U x M x CA-125 1) Ultrasound score (U; transabdominal) – 1 point for each of the 

following: multilocular cyst, evidence of solid areas, evidence of metastases, presence of ascites, and bilateral lesions U = 0 for US score of 0  =1 for US score of 1  = 3 for US score ≥ 2 

3) Serum CA-125 by RIA (Abbott Labs, Chicago) 4) Menopausal status (M): 1 if premenopausal 3 if postmenopausal 

1) RMI1 with cutoff value of 200 

 Dis+ Dis- Tot T+ 35 3 38 

T- 6 95 101 Tot 41 98 139  Lower Upper  Value 95% CI 95% CI Se 85.4% 74.5% 96.2% Sp 96.9% 93.5% 100.0%PPV 92.1% 83.5% 100.0%NPV 94.1% 89.4% 98.7% 

2) RMI1 with cutoff value of 250 (maximum specificity) 

 Dis+ Dis- Tot T+ 32 1 33 T- 9 97 106 Tot 41 98 139  Lower Upper  Value 95% CI 95% CI Se 78.0% 65.3% 90.7% Sp 99.0% 97.0% 100.0%PPV 97.0% 91.1% 100.0%NPV 91.5% 86.2% 96.8% 

3) RMI1 with cutoff value of 25 (maximum Se) 

 Dis+ Dis- Tot T+ 41 37 78 T- 0 61 61 Tot 41 98 139  Lower Upper  Value 95% CI 95% CI Se 100.0% 92.7% 100.0%Sp 62.2% 52.6% 71.8% PPV 52.6% 41.5% 63.6% NPV 100.0% 95.1% 100.0%
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Results were reported, but have not been abstracted, for the following combinations: RMI 1with cutoff values of 50, 75, 100, 150 

 Se Sp 50 95.1% 76.5% 

75 92.7% 84.7% 100 85.4% 87.8% 150 85.4% 93.9% 

Lu, Van Gestel, Suykens, et al., 2003 #1730 

Geographical location: Leuven, Belgium Dates: 1994-1999 1994-1997 (training) 1997-1999 (test) Size of population: 525 women 265 (training set) 160 (test set) Retrospective case series Reference standard: Histopathologic diagnosis Reference standard applied to all test negatives?: Yes Statistical tests used: Se, Sp, ROC curves Blinding: None 

Age: NR Menopausal status (n [%]): NR Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Women referred for US to single ultrasonographer with persistent extrauterine pelvic mass which was subsequently surgically removed Exclusion criteria: 

No preoperative CA125 assay (n = 100) 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): 525 (100%) Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Multivariable models developed using least squares support vector machine (LS-SVM) classifiers in a Bayesian evidence framework. Model built on 265 patient training set; tested on 160-patient test set. Candidate variables included 27 demographic, serum marker, color Doppler, B-mode US, US morphologic, and US echogenicity variables. Variables were chosen using forward selection. Six different models were built and tested 2) LR1- logistic regression 3) LS-SVM1 (Lin) 4) LS-SVM1 (RBF) 5) LR2 

1) RMI1 with cutoff value of 75 

 Dis+ Dis- Tot T+ 44 27 71 

T- 10 79 89 Tot 54 106 160  Lower Upper  Value 95% CI 95% CI Se 81.5% 71.1% 91.8% Sp 74.5% 66.2% 82.8% PPV 62.0% 50.7% 73.3% NPV 88.8% 82.2% 95.3% 

AUC = 0.8733 (± 0.0298 SE) 2) RMI1 with cutoff value of 100 

 Dis+ Dis- Tot T+ 40 21 61 T- 14 85 99 Tot 54 106 160  Lower Upper  Value 95% CI 95% CI Se 74.1% 62.4% 85.8% Sp 80.2% 72.6% 87.8% PPV 65.6% 53.7% 77.5% NPV 85.9% 79.0% 92.7% 

Results were reported, but have not been abstracted, for the following 
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Definition of positive and negative on screening test: 

6) LS-SVM2 (Lin) 7) LS-SVM2 (RBF) 8) RMI1 (Jacobs, Oram, Fairbanks, et al., 1990 [#6820]) 

combinations: Models 2-7 have Se, Sp, PPV and NPV for 3 to 4 cutoff values each and AUC reported. Each performs better than RMI1. 
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Ma, Shen, and Lang, 2003 #1900 

Geographical location: Beijing, China Dates: Jan 1998-Jun 1999 Size of population: 140 women Single-institution retrospective case series Reference standard: Not stated explicitly, but implied that all patients had pathological classification Reference standard applied to all test negatives?: Yes, presumably Statistical tests used: Se, Sp, PPV Blinding: None Definition of positive and negative on screening test: Used definitions of Tingulstad, Hagen, Skjeldestad, et al., 1996 (#3890), but analyzed multiple cutoff values 

Age: Range: 30 - NR Menopausal status (n [%]): Pre: 89 (64%) Post: 51 (36%) > 1 year of amenorrhea or age > 50 if status post hysterectomy Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: “Ovarian neoplasm” patients over 30 years admitted to a single institution Exclusion criteria: 

NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) RMI2 (Tingulstad, Hagen, Skjeldestad, et al., 1996 [#3890]) – clinical prediction rule developed from logistic regression model based on ultrasound (U), CA125, and menopausal status (M) RMI2 = U x M x CA-125 2) Ultrasound (U; transabdominal) scored 1 point for each of the following characteristics: multilocular cyst, evidence of solid areas, 

evidence of metastases, presence of ascites, and bilateral lesions. U = 1 for total score of 0-1 4 for total score ≥ 2 

3) Serum CA-125 4) Menopausal status (M): 1 if premenopausal 4 if postmenopausal 

1) RMI2 cutoff value 200 

 Dis+ Dis- Tot T+ 55 12 67 

T- 8 65 73 Tot 63 77 140  Lower Upper  Value 95% CI 95% CI Se 87.3% 79.1% 95.5% Sp 84.4% 76.3% 92.5% PPV 82.1% 72.9% 91.3% NPV 89.0% 81.9% 96.2% 

2) RMI2 cutoff value 100 

 Dis+ Dis- Tot T+ 59 21 80 T- 4 56 60 Tot 63 77 140  Lower Upper  Value 95% CI 95% CI Se 93.7% 87.7% 99.7% Sp 72.3% 62.3% 82.3% PPV 73.8% 64.1% 83.4% NPV 93.3% 87.0% 99.6% 

Results were reported, but have not been abstracted, for the following combinations: RMI2 with cutoff of 50, 400, 1000 
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Maggino, Gadducci, D’Addario, et al., 1994 #4500 

Geographical location: Italy Dates: Mar 1991-Mar 1992 Size of population: 383 women 48 excluded for inadequate data 335 evaluable 45 benign cysts 290 surgical cases Case series Reference standard: Histopathological diagnosis in 290 women; clinical and US followup in 45 patients with benignappearing cysts Reference standard applied to all test negatives?: 45 women with US findings indicating benign cyst and CA125 < 35 U/ml not verified Statistical tests used: Se, Sp, PPV, NPV Blinding: None Definition of positive and negative on screening test: Yes 

Age: Mean: 61.9 Range: 40-91 Menopausal status (n [%]): Post: 290 (100%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Postmenopausal women with pelvic mass (intra- or extraadnexal) Exclusion criteria: 

Premenopause; previous malignant neoplasia (except breast cancer); previous bilateral adnexectomy; if > 55 years of age, previous hysterectomy for nontumoral disease 

Symptomatic (n [%]): 209 (72%) Detected by exam (n [%]): All patients Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Gynecologic examination 2) US (transabdominal) Classified as: Benign if size < 5 cm; wall clear, thin; nonechogenous content; no septa or ≤ 3 thin septa; 

no free liquid in pouch of Douglas; Equivocal if size 5-10 cm; wall clear, smooth, thick; hypoechogenic liquid content or solild homogeneous content; >3 thin septa; thick but regular septa; absence of endocystic vegetation; absence of free peritoneal fluid; Malignant if none of above features observed 3) CA-125: T- < 35 U/ml Borderline 35-65 U/ml T+ > 65 U/ml 4) Combination of US and CA-125 T+ if either individual test abnormal T- if neither test abnormal 

1) Combined US (Gr III possibly malignant) or CA-125 (> 65 U/ml) as T+; else, TAnalysis limited to ovarian tumors 

 Dis+ Dis- Tot T+ 100 36 136 

T- 6 98 104 Tot 106 134 240  Lower Upper  Value 95% CI 95% CI Se 94.3% 89.9% 98.7% Sp 73.1% 65.6% 80.6% PPV 73.5% 66.1% 80.9% NPV 94.2% 89.7% 98.7% 

2) Combined US (Gr III possibly malignant) or CA-125 (> 35 U/ml) as T+; else, TAnalysis limited to ovarian tumors 

 Dis+ Dis- Tot T+ 102 45 147 T- 4 89 93 Tot 106 134 240  Lower Upper  Value 95% CI 95% CI Se 96.2% 92.6% 99.9% Sp 66.4% 58.4% 74.4% PPV 69.4% 61.9% 76.8% NPV 95.7% 91.6% 99.8% 

3) Combined US (Gr II-III possibly malignant or borderline) or CA-125 (> 65 U/ml) as T+; else, TAnalysis limited to ovarian tumors 

 Dis+ Dis- Tot T+ 106 77 183 T- 0 57 57 Tot 106 134 240 
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 Lower Upper  Value 95% CI 95% CI Se 100.0% 97.2% 100.0%

Sp 42.5% 34.2% 50.9% PPV 57.9% 50.8% 65.1% NPV 100.0% 94.7% 100.0%

4) Combined US (Gr II-III possibly malignant or borderline) or CA-125 (>35 U/ml) as T+; else, TAnalysis limited to ovarian tumors 

 Dis+ Dis- Tot T+ 106 82 188 T- 0 52 52 Tot 106 134 240  Lower Upper  Value 95% CI 95% CI Se 100.0% 97.2% 100.0%Sp 38.8% 30.6% 47.1% PPV 56.4% 49.3% 63.5% NPV 100.0% 94.2% 100.0%

5) CA-125 > 65 

 Dis+ Dis- Tot T+ 76 10 86 T- 30 124 154 Tot 106 134 240  Lower Upper  Value 95% CI 95% CI Se 71.7% 63.1% 80.3% Sp 92.5% 88.1% 97.0% PPV 88.4% 81.6% 95.1% NPV 80.5% 74.3% 86.8% 

6) US T+ Class III (possibly malignant) analysis limited to ovarian tumors (nonovarian tumors excluded) 

 Dis+ Dis- Tot T+ 90 30 120
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T- 16 104 120 Tot 106 134 240  Lower Upper  Value 95% CI 95% CI Se 84.9% 78.1% 91.7% Sp 77.6% 70.6% 84.7% PPV 75.0% 67.3% 82.7% NPV 86.7% 80.6% 92.7% 

Results were reported, but have not been abstracted, for the following combinations: No other combinations, but the following individual tests: US (Class II-II possibly malignant or borderline as positive) CA-125 (> 35 U/ml as positive) 
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Mancuso, De Vivo, Triolo, et al., 2004 #1610 

Geographical location: Messina, Italy Dates: NR Size of population: 125 women Case series Reference standard: Histopathological diagnosis Reference standard applied to all test negatives?: Yes Statistical tests used: Se, Sp, PPV, NPV Blinding: None Definition of positive and negative on screening test: CA-125 - >35 U/ml US, defined 

Age: Mean: 42.2 Range: 18-82 Menopausal status (n [%]): Pre: 76 (61%) Post: 49 (39%) Race/ethnicity (n [%]): NR Risk factors (n [%]): Nulliparous: 62 (50%) Multiparous: 63 (50%) Inclusion criteria: Women admitted for adnexal mass Exclusion criteria: 

None 

Symptomatic (n [%]): Pain 68 (54%) Menstrual disorder 22 (18%) Urinary/intestinal 5 (4%)Asymptomatic 30 (24%)Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) US (transvaginal) Positive if: solid structure or cystic but complex; irregular walls, endocystic vegetations, thick septa; bilateral lesions; ascites 

2) CA-125 positive if > 35 U/ml 3) Combinations of US, age (> 50 years), CA125, menopause (post) 

1) Combination of US + age > 50 

 Dis+ Dis- Tot T+ 13 10 23 

T- 1 101 102 Tot 14 111 125  Lower Upper  Value 95% CI 95% CI Se 92.9% 79.4% 100.0%Sp 91.0% 85.7% 96.3% PPV 56.5% 36.3% 76.8% NPV 99.0% 97.1% 100.0%

2) Combination of CA-125 + age > 50 

 Dis+ Dis- Tot T+ 13 4 17 T- 1 107 108 Tot 14 111 125  Lower Upper  Value 95% CI 95% CI Se 91.0% 76.0% 100.0%Sp 96.6% 93.2% 100.0%PPV 76.5% 56.3% 96.6% NPV 99.1% 97.3% 100.0%

3) Combination of US + menopause 

 Dis+ Dis- Tot T+ 14 13 27 T- 0 98 98 Tot 14 111 125  Lower Upper  Value 95% CI 95% CI Se 100.0% 78.6% 100.0%Sp 88.7% 82.8% 94.6% PPV 51.9% 33.0% 70.7% NPV 100.0% 96.9% 100.0%

4) Combination of CA-125 + menopause 
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Results 

 Dis+ Dis- Tot T+ 14 4 18 

T- 0 107 107 Tot 14 111 125  Lower Upper  Value 95% CI 95% CI Se 100.0% 78.6% 100.0%Sp 96.6% 93.2% 100.0%PPV 77.8% 58.6% 97.0% NPV 100.0% 97.2% 100.0%

5) Combination of CA-125 + US 

 Dis+ Dis- Tot T+ 14 6 20 T- 0 105 105 Tot 14 111 125  Lower Upper  Value 95% CI 95% CI Se 100.0% 78.6% 100.0%Sp 94.4% 90.1% 98.7% PPV 70.0% 49.9% 90.1% NPV 100.0% 97.1% 100.0%
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Manjunath, Pratapkumar, Sujatha, et al., 2001 #2510 

Geographical location: Manipal, India Dates: Jan 97-Aug 99 Size of population: 152 Registry Reference standard: Pathology Reference standard applied to all test negatives?: Yes – applied to all in population regardless of RMI score Statistical tests used: Chi-square, Se, Sp, PPV, NPV Blinding: NR

Definition of positive and negative on screening test: Ultrasound: 1 point each for: multilocular, solid areas, ascites, bilateral, and intraabdominal metastases Menopausal status: > 1 yr amenorrhea or age > 50 

Age: NR Menopausal status (n [%]): Pre: 84 (57%) Post: 64 (43%) Race/ethnicity (n [%]): NRRisk factors (n [%]): NR Inclusion criteria: Patients who underwent surgery for a pelvic mass Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NRDetected by imaging (n [%]): NRCombination (n [%]): 

NR Additional data used for diagnosis: NR

1) Ultrasound score (U) 

1 point each for: multilocular, solid areas, ascites, bilateral, and intra-abdominal metastases 2) CA-125 3) Menopausal status 4) RMI1 (Jacobs, Oram, Fairbanks, et al., 1990 [#6820]) RMI1 = U x M x CA125, where M = 1 or 3 (pre or post) and U = 0 (no points), 1 (one point) or 3 (2 or more points on ultrasound) 5) RMI2 (Tingulstad, Hagen, Skjeldestad, et al., 1996 [#3890]) RMI2 = U x M x CA125, where M = 1 or 4 (pre or post) and U = 1 (score 0 or 1) or 4 (score 2 or more) 6) RMI3 (Tingulstad et al 1999) RMI3 = U x M x CA125, where M = 1 or 3 (pre or post), U = 1 (score 0 or 1) or 3 (score at least 2) 

Note: Borderline tumors not counted, so n = 148 (appropriate) Note: Results are given for 11 different cutoff scores. The authors recommend cutoff of 200 for all 3 RMIs to minimize false positives. 1) RMI1 (cutoff 200) 

 Dis+ Dis- Tot T+ 68 5 73 

T- 25 50 75 Tot 93 55 148  Lower Upper  Value 95% CI 95% CI Se 73.0% 64.0% 82.0% Sp 91.0% 83.4% 98.6% PPV 93.2% 87.4% 98.9% NPV 66.7% 56.0% 77.3% 

2) RMI2 (cutoff 200) 

 Dis+ Dis- Tot T+ 71 10 81 T- 22 45 67 Tot 93 55 148  Lower Upper  Value 95% CI 95% CI Se 76.0% 67.3% 84.7% Sp 82.0% 71.8% 92.2% PPV 87.7% 80.5% 94.8% NPV 67.2% 55.9% 78.4% 

3) RMI3 (cutoff 125) 

 Dis+ Dis- Tot T+ 74 11 85 T- 19 44 63 Tot 93 55 148  Lower Upper 
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 Value 95% CI 95% CI 

Se 80.0% 71.9% 88.1% 

Sp 80.0% 69.4% 90.6% PPV 87.1% 79.9% 94.2% NPV 69.8% 58.5% 81.2% 

4) RMI3 (cutoff 200) 

 Dis+ Dis- Tot T+ 69 5 74 T- 24 50 74 Tot 93 55 148  Lower Upper  Value 95% CI 95% CI Se 74.0% 65.1% 82.9% Sp 91.0% 83.4% 98.6% PPV 93.2% 87.5% 99.0% NPV 67.6% 56.9% 78.2% 
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Mol, Boll, De Kanter, et al., 2001 #5780 

Geographical location: Utrecht, the Netherlands Dates: 1991-1998 Size of population: 170 women Registry Reference standard: Pathology Reference standard applied to all test negatives?: Yes Statistical tests used: ROC curvesBlinding: NR

Definition of positive and negative on screening test: Per the original reports of the models (cutoffs not specified here) 

Age: Mean: 46.6Range: 20-89 Menopausal status (n [%]): Pre: 109 (64%) Post: 61 (36%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Surgery for an adnexal mass Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NRDetected by imaging (n [%]): NRCombination (n [%]): 

NR Additional data used for diagnosis: NR 

1) Tailor 1997 ref 19 

US, Doppler, age, AUC 0.81 2) Prompeler 1997 ref 22, AUC 0.73 US, menopausal status 3) Jacobs 1990 ref 13 menopause, US, CA125, AUC 0.83 4) Jacobs 1993 ref 23 menopause, US CA125, AUC 0.86 5)Tingulstad 1996 ref 12 menopause, US, CA125, AUC 0.83 6) Timmerman 1999 ref 9 menopause, US, Doppler, CA-125 (neural network), AUC 0.84 7) Timmerman 1999 ref 9 Menopause, US, CA125 (neural network), AUC 0.85 8) Timmerman 1999 ref 9 menopause, US, Doppler, CA-125 (logistic regression), AUC 0.85 

1) Tailor et al., 1997 model sonography, color Doppler, age 

 Dis+ Dis- Tot T+ 27 77 104 

T- 3 63 66 Tot 30 140 170  Lower Upper  Value 95% CI 95% CI Se 90.0% 79.3% 100.0%Sp 45.0% 36.8% 53.2% PPV 26.0% 17.5% 34.4% NPV 95.5% 90.4% 100.0%

2) Prompeler 1997 ref 22, AUC 0.73 U/S, menopausal status 

 Dis+ Dis- Tot T+ 27 91 118 T- 3 49 52 Tot 30 140 170  Lower Upper  Value 95% CI 95% CI Se 90.0% 79.3% 100.0%Sp 35.0% 27.1% 42.9% PPV 22.9% 15.3% 30.5% NPV 94.2% 87.9% 100.0%

3) Jacobs 1990 ref 13 menopause, U/S, CA-125, AUC 0.83 

 Dis+ Dis- Tot T+ 27 69 96 T- 3 71 74 Tot 30 140 170  Lower Upper  Value 95% CI 95% CI Se 90.0% 79.3% 100.0%Sp 51.0% 42.7% 59.3% PPV 28.1% 19.1% 37.1% NPV 95.9% 91.5% 100.0%
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4) Jacobs 1993 ref 23 menopause, U/S CA-125, AUC 0.86 

 Dis+ Dis- Tot T+ 27 55 82 

T- 3 85 88 Tot 30 140 170  Lower Upper  Value 95% CI 95% CI Se 90.0% 79.3% 100.0%Sp 61.0% 52.9% 69.1% PPV 32.9% 22.8% 43.1% NPV 96.6% 92.8% 100.0%

5) Tingulstad 1996 ref 12 menopause, U/S, CA-125, AUC 0.83 

 Dis+ Dis- Tot T+ 27 69 96 T- 3 71 74 Tot 30 140 170  Lower Upper  Value 95% CI 95% CI Se 90.0% 79.3% 100.0%Sp 51.0% 42.7% 59.3% PPV 28.1% 19.1% 37.1% NPV 95.9% 91.5% 100.0%

6) Timmerman 1999 ref 9 menopause, U/S, Doppler, CA-125 (neural network), AUC 0.84 

 Dis+ Dis- Tot T+ 27 56 83 T- 3 84 87 Tot 30 140 170  Lower Upper  Value 95% CI 95% CI Se 90.0% 79.3% 100.0%Sp 60.0% 51.9% 68.1% PPV 32.5% 22.5% 42.6% 
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NPV 96.6% 92.7% 100.0%

7) Timmerman 1999 ref 9 Menopause, U/S, CA-125 (neural network), AUC 0.85 

 Dis+ Dis- Tot T+ 27 76 103 

T- 3 64 67 Tot 30 140 170  Lower Upper  Value 95% CI 95% CI Se 90.0% 79.3% 100.0%Sp 46.0% 37.7% 54.3% PPV 26.2% 17.7% 34.7% NPV 95.5% 90.6% 100.0%

8) Timmerman 1999 ref 9 menopause, U/S, Doppler, CA-125 (logistic regression), AUC 0.85 

 Dis+ Dis- Tot T+ 27 62 89 T- 3 78 81 Tot 30 140 170  Lower Upper  Value 95% CI 95% CI Se 90.0% 79.3% 100.0%Sp 56.0% 47.8% 64.2% PPV 30.3% 20.8% 39.9% NPV 96.3% 92.2% 100.0%
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Morgante, la Marca, Ditto, et al., 1999 #2900 

Geographical location: Siena, Italy Dates: Jan 1995-Dec 1997 Size of population: 124 women Registry Reference standard: Pathology Reference standard applied to all test negatives?: Yes Statistical tests used: Sn,Sp, PPV, NPV, chisquare, ROC curves, Mann-Whitney U, McNemar’s Blinding: NRDefinition of positive and negative on screening test: Different cutoffs are reported for RMI1 and RMI2 

Age: Mean NR Age reported as categorical variable Menopausal status (n [%]): Pre: 69 (56%) Post: 55 (44%) (amenorrhea > 1 yr or age > 50 if status post hysterectomy) Race/ethnicity (n [%]): NRRisk factors (n [%]): NR Inclusion criteria: Age > 30, admitted for surgical evaluation of ovarian mass Exclusion criteria: 

Age < 30, no surgery 

Symptomatic (n [%]): NR Detected by exam (n [%]): NRDetected by imaging (n [%]): NRCombination (n [%]): NR Additional data used for diagnosis: NR 

1) CA-125 2) Menopausal status (M): age 50 if prior hysterectomy or > 1 yr amenorrhea 3) Ultrasound (U; 1 point each for multilocular, solid, bilateral, ascites, intraabdominal mets) RMI1 (Jacobs, Oram, Fairbanks, et al., 1990 [#6820]) RMI1 = U x M x CA125, where U = 0 if score = 0, U = 1 if score = 1, U = 3 if score at least 2; M = 1 if premenopausal, M = 3 if postmenopausal RMI2 (Tingulstad, Hagen, Skjeldestad, et al., 1996 [#3890]) RMI2 = U x M x CA125, where U = 1 if score = 0 or 1, U = 4 if score at least 2; M = 1 if premenopausal, M = 4 if postmenopausal 

1) RMI1 (cutoff 80): 

 Dis+ Dis- Tot T+ 25 19 44 

T- 6 74 80 Tot 31 93 124  Lower Upper  Value 95% CI 95% CI Se 81.0% 67.2% 94.8% Sp 80.0% 71.9% 88.1% PPV 56.8% 42.2% 71.5% NPV 92.5% 86.7% 98.3% 

2) RMI1 (cutoff 200): 

 Dis+ Dis- Tot T+ 18 5 23 T- 13 88 101 Tot 31 93 124  Lower Upper  Value 95% CI 95% CI Se 58.0% 40.6% 75.4% Sp 95.0% 90.6% 99.4% PPV 78.3% 61.4% 95.1% NPV 87.1% 80.6% 93.7% 

3) RMI2 (cutoff 125): 

 Dis+ Dis- Tot T+ 25 9 34 T- 6 84 90 Tot 31 93 124  Lower Upper  Value 95% CI 95% CI Se 81.0% 67.2% 94.8% Sp 90.0% 83.9% 96.1% PPV 73.5% 58.7% 88.4% NPV 93.3% 88.2% 98.5% 

4) RMI2 (cutoff 200): 
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 Dis+ Dis- Tot T+ 23 7 30 T- 8 86 94 Tot 31 93 124  Lower Upper  Value 95% CI 95% CI Se 74.0% 58.6% 89.4% Sp 93.0% 87.8% 98.2% PPV 76.7% 61.5% 91.8% NPV 91.5% 85.8% 97.1% 

Results were reported, but have not been abstracted, for the following combinations: RMI1 and RMI2 at following cutoffs: 25, 50, 80, 100, 125, 150, 200, 250 
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Obeidat, Amarin, Latimer, et al., 2004 #1500 

Geographical location: Cambridge, England Dates: Jan 2000-Dec 2001 Size of population: 100 Registry Reference standard: Pathology Reference standard applied to all test negatives?: Yes Statistical tests used: Chi-square, MannWhitney U Blinding: NR

Definition of positive and negative on screening test: RMI of Jacobs, Oram, Fairbanks, et al., 1990 (#6820) - 4 cutoffs tested: 100, 150, 200, 250 

Age: Range: 30-NR Menopausal status (n [%]): Pre: 27 (27%) Post: 73 (73%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: 100 consecutive women with a pelvic mass who were admitted for laparotomy; age > 30Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NRDetected by imaging (n [%]): 100 (100%)Combination (n [%]): 

NR Additional data used for diagnosis: NR 

1) Menopausal status (M = 1 for pre, M = 3 for post); menopause defined as 1 year amenorrhea, or 50 years old for patients with prior hysterectomy 2) Ultrasound score (U): 1 point for each: multilocular, solid, bilateral, ascites, intraabdominal metastases; U = 0 for score 0, U = 1 for score 1, U = 3 for score ≥ 2 3) CA-125 RMI1 (Jacobs, Oram, Fairbanks, et al., 1990 [#6820]) RMI1 = M x U x CA-125 

1) RMI1, cutoff 100: 

 Dis+ Dis- Tot T+ 69 17 86 

T- 3 11 14 Tot 72 28 100  Lower Upper  Value 95% CI 95% CI Se 96.0% 91.5% 100% Sp 39.0% 20.9% 57.1% PPV 80.2% 71.8% 88.6% NPV 78.6% 57.1% 100% 

2) RMI1, cutoff 150: 

 Dis+ Dis- Tot T+ 68 9 77 T- 4 19 23 Tot 72 28 100  Lower Upper  Value 95% CI 95% CI Se 95.0% 90.0% 100.0%Sp 68.0% 50.7% 85.3% PPV 88.3% 81.1% 95.5% NPV 82.6% 67.1% 98.1% 

3) RMI1, cutoff 200: 

 Dis+ Dis- Tot T+ 65 3 68 T- 7 25 32 Tot 72 28 100  Lower Upper  Value 95% CI 95% CI Se 90.0% 83.1% 96.9% Sp 89.0% 77.4% 100% PPV 95.6% 90.7% 100% NPV 78.1% 63.8% 92.4% 

4) RMI1 cutoff 250: 
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 Dis+ Dis- Tot T+ 62 3 65 T- 10 25 35 Tot 72 28 100  Lower Upper  Value 95% CI 95% CI Se 86.0% 78.0% 94.0% Sp 89.0% 77.4% 100.0%PPV 95.4% 90.3% 100.0%NPV 71.4% 56.5% 86.4% 

Results were reported, but have not been abstracted, for the following combinations: “AUC = 0.91” 
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Roman, Muderspach, Stein, et al., 1997 #6160 

Geographical location: Los Angeles, CA Dates: Jul 1992-Mar 1994 Size of population: 226 women (nonconsecutive) Registry Reference standard: Pathology Reference standard applied to all test negatives?: Statistical tests used: Chi-square, logistic regressionBlinding: NR Definition of positive and negative on screening test: See Scoring column 

Age: NR Menopausal status (n [%]): Pre: 181 (80%) Post: 45 (20%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Operative intervention for presumed adnexal mass Exclusion criteria: 

Emergency surgery, clinical or radiographic evidence of metastatic disease 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Pelvic exam; fixed, irregular or associated with ascites = suspicious 2) CA-125 > 35 U/ml 3) AFP > 10 ng/ml in non-pregnant patient 4) LDH > 350 U/l 5) TVUS; suspicious masses are those which are cystic with one large or multiple nodules or 

cystic/solid, and solid masses not arising from the uterus 6) Doppler; pulsatility index less than 1.0 or resistance index ≤ 0.4 are suspicious 7) HCG >15 mIU/ml in a non-pregnant patient 

1) Pelvic exam, serum tumor marker, or US positive; postmenopausal women only; low malignant potential tumors counted as Disease + 

 Dis+ Dis- Tot T+ 15 15 30 

T- 0 13 13 Tot 15 28 43  Lower Upper  Value 95% CI 95% CI Se 100.0% 80.0% 100.0%Sp 46.4% 28.0% 64.9% PPV 50.0% 32.1% 67.9% NPV 100.0% 76.9% 100.0%

2) Serum tumor markers and ultrasound, T+ if serum markers above threshold or US “suspicious” postmenopausal women only 

 Dis+ Dis- Tot T+ 15 11 26 T- 1 18 19 Tot 16 29 45  Lower Upper  Value 95% CI 95% CI Se 93.8% 81.9% 100.0%Sp 62.1% 44.4% 79.7% PPV 57.7% 38.7% 76.7% NPV 94.7% 84.7% 100.0%

3) Fitted LR model using tumor markers and ultrasound, cut off probability of malignancy = 0.50; postmenopausal women only Same 2x2 table as #2 above Results were reported, but have not been abstracted, for the following combinations: PE + US (Premenopausal and all) 
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PE, tumor markers + US PE + tumor markers Tumor markers + US Postmenopausal women 

Schutter, Kenemans, Sohn, et al., 1994 #940 

Geographical location: Amsterdam, The Netherlands Dates: Nov 1990-Dec 1992 Size of population: 276Æ excluded 48 who did not meet inclusion criteriaÆ 228 

Registry Reference standard: Pathology Reference standard applied to all test negatives?: Yes Statistical tests used: Se, Sp, PPV, NPV, chi-square, Fishers exact, ROC curves, logistic regression Blinding: NR Definition of positive and negative on screening test: Logistic regression model: Exam: benign (0) or malignant (1) 

Age: NR Menopausal status (n [%]): Post: 228 (100%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Pelvic mass; age > 45; amenorrhea > 12 months; scheduled for surgery with biopsy or excision of mass; no history of BSO; no history of malignancy Exclusion criteria: Age ≥ 45; amenorrhea < 12 months; 

additional malignnancy; physical exam “indeterminate;” no pre-operative CA-125

Symptomatic (n [%]): NR Detected by exam (n [%]): 199/228 (87%)Detected by imaging (n [%]): 28/228 (12%) Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Pelvic examination: abnormal if a mass distinguishable from the uterus was identified. Clinician was asked to characterize mass as benign (0) or malignant (1) 

2) TVUS; used Finkler scoring system (ref#3, Table 3). A score of 7 or more was considered positive for malignancy (1). 3) Serum CA-125 >35 (1) is “malignant” 

1) Physical exam, TVUS, and CA-125 all positive defines malignancy 

 Dis+ Dis- Tot T+ 19 3 22 

T- 11 36 47 Tot 30 39 69  Lower Upper  Value 95% CI 95% CI Se 62.0% 44.6% 79.4% Sp 92.0% 83.5% 100.0%PPV 86.4% 72.0% 100.0%NPV 76.6% 64.5% 88.7% 

2) Physical exam and TVUS both positive defines malignancy 

 Dis+ Dis- Tot T+ 38 13 51 T- 8 47 55 Tot 46 60 106  Lower Upper  Value 95% CI 95% CI Se 83.0% 72.1% 93.9% Sp 79.0% 68.7% 89.3% PPV 74.5% 62.5% 86.5% NPV 85.5% 76.1% 94.8% 

3) TVUS and CA-125 positive defines malignancy 

 Dis+ Dis- Tot T+ 20 5 25 T- 12 38 50 Tot 32 43 75  Lower Upper 
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CA-125 ≤ 35 U/ml (0) 

or > 35 (1) Ultrasound score < 7 (0) or ≥ 7 (1) 

 Value 95% CI 95% CI Se 64.0% 47.4% 80.6% 

Sp 89.0% 79.6% 98.4% PPV 80.0% 64.3% 95.7% NPV 76.0% 64.2% 87.8% 

4) Logistic regression model Z = -9.2378 + 2.2506(PE) + 1.6025(US) + 1.7293(CA-125). Probability of malignancy is 1/1+e exp(-z). “The ability to predict malignancy or benignancy of the pelvic mass appeared to be 81.5%”. No AUC given. Results were reported, but have not been abstracted, for the following combinations: All possible combinations of ultrasound, CA-125, and exam findings. 
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Schutter, Sohn, Kristen, et al., 1998 #730 

Geographical location: The Netherlands Dates: Nov 1990-Dec 1992 Size of population: 155 (151 could be classified as malignant or benign; 4 borderlines not included in analysis) Registry Reference standard: Histopathology Reference standard applied to all test negatives?: Yes Statistical tests used: Se, Sp, PPV, NPV, ROC curves, logistic regressionBlinding: NR

Definition of positive and negative on screening test: See Scoring column for individual tests. See Results column for logistic regression equation 

Age: NR Menopausal status (n [%]): Post: 155 (100%) Race/ethnicity (n [%]): NRRisk factors (n [%]): NR Inclusion criteria: Patients presenting with a pelvic mass who underwent surgery Exclusion criteria: Storage problems making sera unusable 

Symptomatic (n [%]): NR Detected by exam (n [%]): NRDetected by imaging (n [%]): NRCombination (n [%]): 

NR Additional data used for diagnosis: NR 

1) Physical exam: malignant or benign 2) Ultrasound: Finkler score* 7-10 positive, 1-6 negative 3) CA-125: ≥ 35 positive 4) CA72-4: ≥ 3 positive *Finkler score (Finkler et al 1988, ref #25) 1-cyst/smooth borders 2-cyst/irregular borders 3-cyst/echoes and irregular borders 4-6-equivocal 7-9-multiseptated or irregular cystic mass 10-pelvic mass with ascites 

1) PE/US/CA-125/CA-72-4: 

 Dis+ Dis- Tot T+ 27 0 27 

T- 32 92 124 Tot 59 92 151  Lower Upper  Value 95% CI 95% CI Se 46.0% 33.3% 58.7% Sp 100.0% 96.7% 100.0%PPV 100.0% 88.9% 100.0%NPV 74.2% 66.5% 81.9% 

2) PE/US: 

 Dis+ Dis- Tot T+ 47 12 59 T- 12 80 92 Tot 59 92 151  Lower Upper  Value 95% CI 95% CI Se 80.0% 69.8% 90.2% Sp 87.0% 80.1% 93.9% PPV 79.7% 69.4% 89.9% NPV 87.0% 80.1% 93.8% 

3) Logistic regression model: 

1/(1+e-z) where Z = -

5.6816+2.2677*(US)-2.4928*(PE)+1.6057*(CA125)+1.5866*(CA72-4) 

 Dis+ Dis- Tot T+ 48 9 57 

T- 11 83 94 Tot 59 92 151  Lower Upper  Value 95% CI 95% CI Se 81.4% 71.4% 91.3% Sp 90.2% 84.1% 96.3% PPV 84.2% 74.7% 93.7% 
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NPV 88.3% 81.8% 94.8% 

4) US/CA-125/CA-72-4: 

 Dis+ Dis- Tot T+ 28 1 29 

T- 31 91 122 Tot 59 92 151  Lower Upper  Value 95% CI 95% CI Se 47.0% 34.3% 59.7% Sp 99.0% 97.0% 100.0%PPV 96.6% 89.9% 100.0%NPV 74.6% 66.9% 82.3% 

5) PE/US/CA-125: 

 Dis+ Dis- Tot T+ 34 5 39 T- 25 87 112 Tot 59 92 151  Lower Upper  Value 95% CI 95% CI Se 57.6% 45.0% 70.2% Sp 94.6% 89.9% 99.2% PPV 87.2% 76.7% 97.7% NPV 77.7% 70.0% 85.4% 

Results were reported, but have not been abstracted, for the following combinations: PE/US/CA-72-4 CA-125/CA-72-4 PE/CA-125/CA-72-4 PE/CA-125 PE/CA-72-4 US/CA-125 US/CA-72-4 
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Strigini, Gadducci, Del Bravo, et al., 1996 #4000 

Geographical location: Pisa, Italy Dates: Jan 1993-Jun 1994 Size of population: 109 total Æ 34 postmenopausal are reported here Registry Reference standard: Pathology Reference standard applied to all test negatives?: Yes Statistical tests used: Se, Sp Blinding: NR Definition of positive and negative on screening test: See Scoring column 

Age: Median: 43 Range: 18-80 Menopausal status (n [%]): Post: 34 (31%) Race/ethnicity (n [%]): NR Risk factors (n [%]): NR Inclusion criteria: Surgery scheduled for an adnexal mass Exclusion criteria: 

NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NR Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Transvaginal ultrasound (TVUS) Classified masses as probably benign or malignant. Malignancy was defined as “solid portions with irregular structure, thick septae or papillae, irregular margins” 

2) Doppler: pulsatility index < 1 was considered abnormal (reference #5 Kurjak ). If no color flow was detected in the mass the Doppler was considered negative (benign). 3) CA-125 > 65 U/ml reference #11) 

1) TVUS or CA-125 /postmenopausal only 

 Dis+ Dis- Tot T+ 12 3 15 

T- 1 18 19 Tot 13 21 34  Lower Upper  Value 95% CI 95% CI Se 92.0% 77.3% 100.0%Sp 86.0% 71.2% 100.0%PPV 80.0% 59.8% 100.0%NPV 94.7% 84.7% 100.0%

2) TVUS and CA-125/postmenopausal only 

 Dis+ Dis- Tot T+ 6 1 7 T- 7 20 27 Tot 13 21 34  Lower Upper  Value 95% CI 95% CI Se 46.0% 18.9% 73.1% Sp 95.0% 85.7% 100.0%PPV 85.7% 59.8% 100.0%NPV 74.1% 57.5% 90.6% 

3) TVUS or PI/postmenopausal only 

 Dis+ Dis- Tot T+ 12 5 17 T- 1 16 17 Tot 13 21 34  Lower Upper  Value 95% CI 95% CI Se 92.0% 77.3% 100.0%Sp 76.0% 57.7% 94.3% PPV 70.6% 48.9% 92.2% NPV 94.1% 82.9% 100.0%
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4) TVUS and PI/postmenopausal only 

 Dis+ Dis- Tot T+ 9 1 10 

T- 4 20 24 Tot 13 21 34  Lower Upper  Value 95% CI 95% CI Se 69.0% 43.9% 94.1% Sp 95.0% 85.7% 100.0%PPV 90.0% 71.4% 100.0%NPV 83.3% 68.4% 98.2% 
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Tailor, Jurkovic, Bourne, et al., 1999 #2910 

Geographical location: London, UK Dates: 

NR Size of population: 67 Registry Reference standard: Pathology Reference standard applied to all test negatives?: 

Yes

Statistical tests used: ROC curves, logistic regression model using the network output gives probability of malignancyBlinding: 

NR

Definition of positive and negative on screening test: Logistic regression model using the neural network output gives the probability of malignancy 

Age: Mean: 39.6 Premenopausal (n = 45): mean age 38, range 20-52 Postmenopausal (n = 22): mean age 61, range 48-76 Menopausal status (n [%]): Pre (< 45): 45 (67%)Post (> 55): 22 (33%) Race/ethnicity (n [%]): NRRisk factors (n [%]): NR Inclusion criteria: Pelvic mass and scheduled for surgeryExclusion criteria: No histologic specimen obtained 

Symptomatic (n [%]): NR Detected by exam (n [%]): NRDetected by imaging (n [%]): NRCombination (n [%]): NR Additional data used for diagnosis: NR 

1) Age 2) Menopausal status 

3) Tumor diameter 4) Tumor volume 5) Locularity 6) Presence of papillations 7) Echogenicity 8) Blood flow velocity waveforms 9) Peak systolic velocity 10) Time-average maximum velocity (TAMXV) 11) Pulsatility index 12) Resistance index Note: “best model” uses the following variables: age, maximum diameter, papillary projections, TAMXV 

1) Neural network “best model” (entire data set); ROC AUC = 0.9987: 

 Dis+ Dis- Tot T+ 14 0 14 

T- 1 52 53 Tot 15 52 67  Lower Upper  Value 95% CI 95% CI Se 93.3% 80.6% 100.0%Sp 100.0% 94.2% 100.0%PPV 100.0% 78.6% 100.0%NPV 98.1% 94.5% 100.0%

Training set n = 52 Test set n = 15 Data shown are for all cases, including training set 
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Timmerman, Bourne, Tailor, et al., 1999 #2930 

Geographical location: Belgium and UK Dates: Aug 1994-Jul 1996 Size of population: 191 Prospective study of patients with a mass sent for U/S (consented prior to ultrasound and surgery) Reference standard: Pathology Reference standard applied to all test negatives?: Yes Statistical tests used: Multivariate logistic regression, ROC curves/AUC, MannWhitney U, student t, chi-square, Fisher exact Blinding: NR, but prospective Definition of positive and negative on screening test: 

Age: Mean: 51.4 Benign (n = 140): mean (SD) = 49 (16) Malignant (n = 51): mean (SD) = 58 (14) Menopausal status (n [%]): Pre: 99 (51.8%) Post: 92 (48.2%) Benign (n = 140): 40% postmenopausal Malignant (n = 51): 71% postmenopausalRace/ethnicity (n [%]): NRRisk factors (n [%]): NR Inclusion criteria: At least 1 adnexal mass; performance of TVUS with color Doppler; surgical removal of mass Exclusion criteria: 

Surgery not done 

Symptomatic (n [%]): NR Detected by exam (n [%]): NRDetected by imaging (n [%]): NRCombination (n [%]): NR Additional data used for diagnosis: NR 

(A) RMI1: calculated 

per Jacobs, Oram, Fairbanks, et al., 1990 (#6820) using US, menopausal status, and CA-125 (B)Variables included in the final multivariable model: 1) Papillary structures in mass > 3 mm 2) Serum CA-125 3) Color score (subjective from 1-4 depending on amount of blood flow) 4) Menopausal score (can’t find exact criteria – unclear if same as criteria used for RMI1) Multivariate model: Probability of malignancy = 1/(1-e-z) Where z=(2.6369 x color score) + (0.0225 x CA-125) + (7.1062 x papillations > 3 mm score) + (2.6423 x postmenopausal score) - 13.6796 (C) Morphologic Scoring system (Lerner, ref#18)-details not given on how it was calculated 

1) RMI1 with cutoff of 200; AUC = 0.882 

 Dis+ Dis- Tot T+ 33 11 44 

T- 16 113 129 Tot 49 124 173  Lower Upper  Value 95% CI 95% CI Se 67.3% 54.2% 80.4% Sp 91.1% 86.1% 96.1% PPV 75.0% 62.2% 87.8% NPV 87.6% 81.9% 93.3% 

2) Logistic regression model, n = 173 cutoff > 25% probability of malignancy; AUC = 0.967: 

 Dis+ Dis- Tot T+ 47 16 63 T- 2 108 110 Tot 49 124 173  Lower Upper  Value 95% CI 95% CI Se 95.9% 90.4% 100.0%Sp 87.1% 81.2% 93.0% PPV 74.6% 63.9% 85.4% NPV 98.2% 95.7% 100.0%

3) Logistic regression model, n = 173, cutoff > 50% probability of malignancy, AUC = 0.967: 

 Dis+ Dis- Tot T+ 43 10 53 T- 6 114 120 Tot 49 124 173  Lower Upper  Value 95% CI 95% CI Se 87.8% 78.6% 96.9% Sp 91.9% 87.1% 96.7% 
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PPV 81.1% 70.6% 91.7% NPV 95.0% 91.1% 98.9% 

4) Morphologic Index of Lerner (ref #18), AUC = 0.840: 

 Dis+ Dis- Tot T+ 49 55 104 

T- 2 85 87 Tot 51 140 191  Lower Upper  Value 95% CI 95% CI Se 96.1% 90.8% 100.0%Sp 60.7% 52.6% 68.8% PPV 47.1% 37.5% 56.7% NPV 97.7% 94.6% 100.0%

Results were reported, but have not been abstracted, for the following combinations: RMI1 for cutoffs of 50, 75, 100, 150 (n = 173 patients who had CA-125 available AUC = 0.882) Timmerman model for training set (n = 116) and testing set (n = 57) but numbers NR for these subgroups 
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Timmerman, Verrelst, Bourne, et al., 1999 #5940 

Geographical location: Leuven, Belgium Dates: Aug 1994-Aug 1996 Size of population: 173 Registry Reference standard: Pathology Reference standard applied to all test negatives?: Yes Statistical tests used: Logistic regression model, ROC curves/AUC Blinding: NR

Definition of positive and negative on screening test: 

Age: Mean: 53 Range: 22-93 Menopausal status (n [%]): Pre (< 45): 83 (48%)Post (> 55): 90 (52%) Race/ethnicity (n [%]): NRRisk factors (n [%]): NR Inclusion criteria: Adnexal mass; scheduled for surgery; had a CA125 Exclusion criteria: No CA-125 

Symptomatic (n [%]): NR Detected by exam (n [%]): NRDetected by imaging (n [%]): NRCombination (n [%]): 

NR Additional data used for diagnosis: NR 

1) Neural Network 1 uses: menopause score (0 or 1), color score (1-4 subjective), papillations score (0 or 1), CA-125 

2) Neural Network 2 uses: menopausal score (0 or 1), CA-125, ascites (0 or 1), unilocularity (0 or 1), papillations score (0 or 1), smooth walls score (0 or 1), bilaterality score (0 or 1), unilocular score (0 or 1) 3) Logistic Regression 2 uses: menopausal score (0 or 1), CA-125, ascites (0 or 1), unilocularity (0 or 1), smoothe walls (0 or 1), papillations (0 or 1), bilaterality (0 or 1) z=0.5948 meno + 0.0205CA-125 + 0.5446ascites - 0.762unilocular -1.1606smoothe + 1.5049papillations + 0.7633bilateral - 1.0889 4) RMI1 (Jacobs, Oram, Fairbanks, et al., 1990 [#6820]) uses: menopausal score, ultrasound score, CA125 

1) Neural Network 1 (AUC = 0.971) cutoff 45% probability of malignancy 

 Dis+ Dis- Tot T+ 46 12 58 

T- 3 112 115 Tot 49 124 173  Lower Upper  Value 95% CI 95% CI Se 93.9% 87.2% 100.0%Sp 90.3% 85.1% 95.5% PPV 79.3% 68.9% 89.7% NPV 97.4% 94.5% 100.0%

2) Neural Network 2 (AUC = 0.979) cutoff 60% probability of malignancy 

 Dis+ Dis- Tot T+ 47 8 55 T- 2 116 118 Tot 49 124 173  Lower Upper  Value 95% CI 95% CI Se 95.9% 90.3% 100.0%Sp 93.5% 89.2% 97.8% PPV 85.5% 76.1% 94.8% NPV 98.3% 96.0% 100.0%

3) Logistic Regression 2 (AUC = 0.956) cutoff 60% probability of malignancy 

 Dis+ Dis- Tot T+ 47 18 65 T- 2 106 108 Tot 49 124 173  Lower Upper  Value 95% CI 95% CI Se 95.9% 90.3% 100.0%Sp 85.5% 79.3% 91.7% PPV 72.3% 61.4% 83.2% 
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NPV 98.1% 95.6% 100.0%

Tingulstad, Hagen, Skjeldestad, et al., 1996 #3890 

Geographical location: Trondheim, Norway Dates: Feb 1992-Feb 1994 Size of population: 173 Registry Reference standard: Pathology Reference standard applied to all test negatives?: Yes Statistical tests used: Se, Sp, chi-square, ROC curves Blinding: NR

Definition of positive and negative on screening test: RMI1 = U x M x CA125, where U = 0, 1, or 3; M = 1 or 3 RMI2 = U x M x CA125, where U = 0, 1, or 4; M = 1 or 4 

Age: NR Menopausal status (n [%]): Pre (< 45): 82 (47%)Post (> 55): 91 (53%) Race/ethnicity (n [%]): NRRisk factors (n [%]): NR Inclusion criteria: Admitted for surgery for a pelvic mass Exclusion criteria: NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NRDetected by imaging (n [%]): NRCombination (n [%]): 

NR Additional data used for diagnosis: NR 

1) Ultrasound score (U) Based on presence of multilocular cystic lesions, solid areas, bilateral lesions, ascites, and intraabdominal metastases scored 1 point each: If score = 0, then U = 0 

If score = 1, then U = 1 If score ≥ 2, the U = 3 2) Menopause score (M): Premenopausal = 1 Postmenopausal = 3 3) CA-125 in kU/L RMI1 (Jacobs, Oram, Fairbanks, et al., 1990 [#6820]) RMI1 = M x U x CA-125 RMI2 (Tingulstad, Hagen, Skjeldestad, et al., 1996 [#3890]) RMI2 = M x U x CA-124 as RMI1 except U = 1 if total is 0 or 1 4 if total ≥ 2; M = 1 or 4 

1) RMI1 cutoff 50: 

 Dis+ Dis- Tot T+ 49 22 71 

T- 7 95 102 Tot 56 117 173  Lower Upper  Value 95% CI 95% CI Se 88.0% 79.5% 96.5% Sp 81.0% 73.9% 88.1% PPV 69.0% 58.3% 79.8% NPV 93.1% 88.2% 98.0% 

2) RMI1 cutoff 100: 

 Dis+ Dis- Tot T+ 44 9 53 T- 12 108 120 Tot 56 117 173  Lower Upper  Value 95% CI 95% CI Se 79.0% 68.3% 89.7% Sp 92.0% 87.1% 96.9% PPV 83.0% 72.9% 93.1% NPV 90.0% 84.6% 95.4% 

3) RMI1 cutoff 200: 

 Dis+ Dis- Tot T+ 40 5 45 T- 16 112 128 Tot 56 117 173  Lower Upper  Value 95% CI 95% CI Se 71.0% 59.1% 82.9% Sp 96.0% 92.4% 99.6% PPV 88.9% 79.7% 98.1% NPV 87.5% 81.8% 93.2% 
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4) RMI2 cutoff 100: 

 Dis+ Dis- Tot T+ 47 21 68 

T- 9 96 105 Tot 56 117 173  Lower Upper  Value 95% CI 95% CI Se 84.0% 74.4% 93.6% Sp 82.0% 75.0% 89.0% PPV 69.1% 58.1% 80.1% NPV 91.4% 86.1% 96.8% 

5) RMI2 cutoff 200: 

 Dis+ Dis- Tot T+ 45 9 54 T- 11 108 119 Tot 56 117 173  Lower Upper  Value 95% CI 95% CI Se 80.0% 69.5% 90.5% Sp 92.0% 87.1% 96.9% PPV 83.3% 73.4% 93.3% NPV 90.8% 85.6% 96.0% 

Results were reported, but have not been abstracted, for the following combinations: RMI1 and RMI 2 at the following cutoffs: 25, 50, 80, 100, 125, 150, 250 
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Tingulstad, Hagen, Skjeldestad, et al., 1999 #5950 

Geographical location: Trondheim, Norway Dates: Feb 1995-Jan 1997 Size of population: 365 Registry Reference standard: Pathology Reference standard applied to all test negatives?: Statistical tests used: Chi-square, MannWhitney U, Se, SpBlinding: NR

Definition of positive and negative on screening test: RMI2 = M x U x CA125, where U = 1 or 3; M = 1 or 3 

Age: NR Menopausal status (n [%]): Pre (< 45): 193 (53%) Post (> 55): 172 (47%) Race/ethnicity (n [%]): NRRisk factors (n [%]): NR Inclusion criteria: Age ≥ 30 with pelvic 

masses, scheduled for surgery Exclusion criteria: 

NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): NRDetected by imaging (n [%]): NRCombination (n [%]): 

NR Additional data used for diagnosis: NR 

1) Menopause score,(1 or 3) 

2) Ultrasound score (1 or 3). Incorporates the following: multilocular, solid, bilateral, ascites, metastases 3) CA-125 DOUG: ABOVE LOOKS LIKE A DESCRIPTION OF RMI1???? 

1) RMI2 cutoff 100: 

 Dis+ Dis- Tot T+ 58 61 119 

T- 17 229 246 Tot 75 290 365  Lower Upper  Value 95% CI 95% CI Se 77.0% 67.5% 86.5% Sp 79.0% 74.3% 83.7% PPV 48.7% 39.8% 57.7% NPV 93.1% 89.9% 96.3% 

2) RMI2 cutoff 150: 

 Dis+ Dis- Tot T+ 54 38 92 T- 21 252 273 Tot 75 290 365  Lower Upper  Value 95% CI 95% CI Se 72.0% 61.8% 82.2% Sp 87.0% 83.1% 90.9% PPV 58.7% 48.6% 68.8% NPV 92.3% 89.1% 95.5% 

3) RMI2 cutoff 200: 

 Dis+ Dis- Tot T+ 53 23 76 T- 22 267 289 Tot 75 290 365  Lower Upper  Value 95% CI 95% CI Se 71.0% 60.7% 81.3% Sp 92.0% 88.9% 95.1% PPV 69.7% 59.4% 80.1% NPV 92.4% 89.3% 95.4% 

4) RMI2 cutoff 250: 
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 Dis+ Dis- Tot T+ 53 20 73 T- 23 270 293 Tot 75 290 366  Lower Upper  Value 95% CI 95% CI Se 70.0% 59.6% 80.4% Sp 93.0% 90.1% 95.9% PPV 72.6% 62.4% 82.8% NPV 92.2% 89.1% 95.2% 

Results were reported, but have not been abstracted, for the following combinations: RMI2 cutoff 50 RMI2 cutoff 300 
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Torres, Derchain, Faundes, et al., 2002 #2170 

Geographical location: São Paolo, Brazil Dates: Jan 1996-Mar 98 Size of population: 158 Registry Reference standard: Pathology Reference standard applied to all test negatives?: Yes Statistical tests used: Logistic regression, ROC curves Blinding: NR

Definition of positive and negative on screening test: RMI = U x M x CA-125 Results reported for a cutoff of 150 

Age: NR Menopausal status (n [%]): NRRace/ethnicity (n [%]): NRRisk factors (n [%]): NR Inclusion criteria: Pelvic mass apparently restricted to adnexal; admitted for surgery Exclusion criteria: Known distant metastasis 

Symptomatic (n [%]): NR Detected by exam (n [%]): NRDetected by imaging (n [%]): NRCombination (n [%]): 

NR Additional data used for diagnosis: NR 

1) Ultrasound score (0-

10) (Depriest et al 1993; Sassone et al., 1991) 0- unilocular simple cysts w/regular fine wall or lesion suggesting dermoid cyst 1-multilocular cyst w/regular and smooth wall (< 3 mm) or thick (> 3 mm) or solid homogeneous tumor w/hyperechogenic and well-defined wall 2-Unilocular cyst or multilocular cyst w/fine wall, with irregularity in the wall or septa (> 3 mm) 4-Multilocular cyst w/thick and irregular wall (irregularity in the wall or septa(> 3 mm), and/or irregular septa or cyst /papillary irregularity over 3 mm 5- Complex lesion w/irregularity in surface (< 3 mm) or badlydefined and irregular wall; or solid heterogeneous lesion 10-Complex lesion w/irregularity in surface (< 3 mm) or badly defined and irregular wall; or solid heterogenous lesion +1 ascites +2 wall expansive involvement > 3 mm 2) Menopausal status (1 or 3) 

1) RMI (cutoff 150): 

 Dis+ Dis- Tot T+ 53 19 72 

T- 14 72 86 Tot 67 91 158  Lower Upper  Value 95% CI 95% CI Se 79.0% 69.2% 88.8% Sp 79.0% 70.6% 87.4% PPV 73.6% 63.4% 83.8% NPV 83.7% 75.9% 91.5% 

AUC for RMI=0.90 2) RMI (cutoff 30): 

 Dis+ Dis- Tot T+ 64 40 104 T- 3 51 54 Tot 67 91 158  Lower Upper  Value 95% CI 95% CI Se 96.0% 91.3% 100.0%Sp 56.0% 45.8% 66.2% PPV 61.5% 52.2% 70.9% NPV 94.4% 88.3% 100.0%

3) RMI (cutoff 100): 

 Dis+ Dis- Tot T+ 56 21 77 T- 11 70 81 Tot 67 91 158  Lower Upper  Value 95% CI 95% CI Se 84.0% 75.2% 92.8% Sp 77.0% 68.4% 85.6% PPV 72.7% 62.8% 82.7% NPV 86.4% 79.0% 93.9% 

4) RMI (cutoff 200): 
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3) CA-125 

 Dis+ Dis- Tot T+ 49 13 62 

T- 18 78 96 Tot 67 91 158  Lower Upper  Value 95% CI 95% CI Se 73.0% 62.4% 83.6% Sp 86.0% 78.9% 93.1% PPV 79.0% 68.9% 89.2% NPV 81.3% 73.4% 89.1% 

Results were reported, but have not been abstracted, for the following combinations: RMI cutoff 500 
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Twickler, Forte, SantosRamos, et al., 1999 #3080 

Geographical location: Dallas, TX Dates: Feb 1993-Aug 1996 Size of population: 304 with masses on exam: 217 had surgery 27 had sonographic followup 60 had no followup Prospective study of patients with pelvic masses detected by exam Reference standard: Pathology or clinical followup Reference standard applied to all test negatives?: No – 60 had no followup Statistical tests used: Mann-Whitney U, Fisher exact, linear logistic regression Blinding: NR Definition of positive and negative on screening test: Ovarian tumor index (see Scoring column for definition). 

Age: Mean (SD): 38.6 (12.3) Range: 15-80 Menopausal status (n [%]): NR Race/ethnicity (n [%]): NRRisk factors (n [%]): NR Inclusion criteria: Patients with clinically suspected adnexal masses Exclusion criteria: 

NR 

Symptomatic (n [%]): NR Detected by exam (n [%]): 304 (100%)Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

1) Age (years) 2) Ovarian volume (ml) 3) Morphology scale (1-15) Sassone ref#3 4) PI (-10 x PI) 5) Vessel location: 

Peripheral -10 Central +10 6) Intense echoes -10 Ovarian Tumor Index is the sum of the above scores 

Ovarian Tumor Index AUC=0.91 1) Ovarian Tumor Index cutoff 45: 

 Dis+ Dis- Tot T+ 26 36 62 

T- 5 178 183 Tot 30 214 245  Lower Upper  Value 95% CI 95% CI Se 85.0% 72.2% 97.8% Sp 83.0% 78.0% 88.0% PPV 41.9% 29.7% 54.2% NPV 97.3% 94.9% 99.6% 

(likely rounding error in cell C) 2) Ovarian Tumor Index cutoff 55: 

 Dis+ Dis- Tot T+ 23 19 42 T- 7 195 202 Tot 30 214 244  Lower Upper  Value 95% CI 95% CI Se 78.0% 63.2% 92.8% Sp 91.0% 87.2% 94.8% PPV 54.8% 39.7% 69.8% NPV 96.5% 94.0% 99.1% 

3) Ovarian Tumor Index cutoff 40: 

 Dis+ Dis- Tot T+ 28 54 82 T- 2 161 163 Tot 30 214 245  Lower Upper  Value 95% CI 95% CI Se 93.0% 83.9% 100.0%Sp 75.0% 69.2% 80.8% PPV 34.1% 23.9% 44.4% NPV 98.8% 97.1% 100.0%
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Different cutoffs tested. 

(likely rounding error) 

Valentin, Hagen, Tingulstad, et al., 2001 #2340 

Geographical location: Malmo, Sweden and Trondheim, Norway Dates: NR Size of population: 157 original, 21 excluded due to no surgery, no pathology, etc.Æ 136 included 

Registry Reference standard: Pathology Reference standard applied to all test negatives?: Yes Statistical tests used: Se, Sp, ROC curves Blinding: 

NR

Definition of positive and negative on screening test: Tailor cutoff 50% Timmerman cutoff 50% 

Age: “Slightly older” than population of Tailor et al. (1997)Menopausal status (n [%]): NRRace/ethnicity (n [%]): NRRisk factors (n [%]): NR Inclusion criteria: Adnexal mass diagnosed clinically and scheduled for surgery Exclusion criteria: No surgery; no pathology from surgery available 

Symptomatic (n [%]): NR Detected by exam (n [%]): 157 (100%)Detected by imaging (n [%]): NR Combination (n [%]): NR Additional data used for diagnosis: NR 

A) Tailor method, cutoff 50% (Tailor et al 1997): 1) Age 2) Menopausal status 3) Tumor diameter 4) Tumor volume 5) Locularity 6) Presence of papillations 7) Echogenicity 8) Blood flow velocity waveforms 9) Peak systolic velocity 10) Time-average maximum velocity 11) Pulsatility index 12) Resistance index B) Timmerman method (ref #5): 1) Papillary structures in mass > 3 mm 2) Serum CA-125 3) Color score (subjective from 1-4 depending on amount of 

1) Tailor model, cutoff 50%; AUC=0.87: 

 Dis+ Dis- Tot T+ 24 12 36 

T- 11 86 97 Tot 35 98 133  Lower Upper  Value 95% CI 95% CI Se 69.0% 53.7% 84.3% Sp 88.0% 81.6% 94.4% PPV 66.7% 51.3% 82.1% NPV 88.7% 82.3% 95.0% 

2) Timmerman model, cutoff 50%; AUC = 0.84: 

 Dis+ Dis- Tot T+ 18 11 29 T- 11 42 53 Tot 29 53 82  Lower Upper  Value 95% CI 95% CI Se 62.0% 44.3% 79.7% Sp 79.0% 68.0% 90.0% PPV 62.1% 44.4% 79.7% NPV 79.2% 68.3% 90.2% 

Results were reported, but have not been abstracted, for the following combinations: Tailor model cutoff 25% Timmerman model cutoff 25% 
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blood flow) 4) Menopausal score (exact criteria unclear) 
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Evidence Table 5: Question 5: Among women with suspected benign masses on initial investigation, what are the sensitivity and sp

periodic CA-125 and/or interval ultrasound examinations for detecting malignant masses? How does the interval of testing/definition of c

and predictive value? Study Study Design Patients Clinical 

Presentation 

Monitoring Strategy Results Co

Sc

Castillo, Alcazar, and Jurado, 2004 #8040 

Geographical location: Pamplona, Spain Dates:Jan 1995-Jun 2002 Size of population:8794 total; 215 had simple unilocular cysts Screening study Reference standard:Surgery or followup at 3 and 9 monthsReference standard applied to all test negatives?: Yes

Test reliability established?: Same 

examiner to eliminate interobserver variability Statistical tests used:

Chi-square Blinding: No

Definition of positive and negative on screening test:Increase in cyst size by 1 cm or more Simple cysts (sonolucent with wall 

Age:Mean (SD): 59 (8.7) Menopausal status (n [%]):Post (> 55): 223 (100%) Race/ethnicity (n [%]):NR Risk factors (n [%]):NR Inclusion criteria:Postmenopausal (at least 1 year without menses and older than 45, or hysterectomy with symptoms and older than 50) Exclusion criteria:Previous history of malignancy; history of bilateral oophorectomy Loss to followup:66 (30.6%) (no statistically significant differences in any parameters between those who completed study and those who were lost to followup)Of remaining 149, 34 underwent immediate surgery. 

Symptomatic (n [%]):0 Detected by exam (n [%]):26 (12%) Detected by imaging (n [%]):215 (100%) Combination (n [%]):NR Additional data used for diagnosis:

NR 

Monitoring test:Ultrasound, CA-125 Interval of testing:3 months, then every 6 months Definition of change:Progression: cyst increased in size at least 1 cm Regression: decrease at least 1 cm Resolution: cyst not detected in 2 consecutive exams 

1) Cancer in patients followed: 

 Dis+ Dis- Tot T+ 0 44 44 

T- 1 104 105 Tot 1 148 149  Lower Upper  Value 95% CI 95% CI Se 0.0% 0.0% 0.0% Sp 70.3% 62.9% 77.6% PPV 0.0% 0.0% 0.0% NPV 99.0% 97.2% 100.0%

QuReVeTeSaStBlDetesExNA 
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Monitoring Strategy Results Co

Sc

< 3 cm, no septations, solid areas, or papillary projections) less than 10 cm with CA-125 < 35, or patient choice, followed Length of followup: 

Median 27 months Type of followup:Repeat US and CA125 Followup interval:3 months, then 6 months 

Goldstein, Subramanyam, Snyder, et al., 1989 #10490 

Geographical location: New York, NY Dates:NR, but 3-year time period Size of population:48; 16 followed Case series Reference standard:

Surgery (26) or followup (16) Reference standard applied to all test negatives?: YesTest reliability established?: No

Age:Range: 46-86 Menopausal status (n [%]):Post (> 55): 48 (100%) Race/ethnicity (n [%]):NR Risk factors (n [%]):NR Inclusion criteria:Postmenopausal at least 12 months Exclusion criteria:NR Loss to followup:

6 (12.5%) 

Symptomatic (n [%]):NR Detected by exam (n [%]):NR Detected by imaging (n [%]):NR Combination (n [%]):NR Additional data used for diagnosis:NR 

Monitoring test:Ultrasound Interval of testing:3-6 months Definition of change:NR 

1) Cancer in patients followed: 

 Dis+ Dis- Tot T+ 0 2 2 

T- 0 14 14 Tot 0 16 16  Lower Upper  Value 95% CI 95% CI Se - - - Sp 87.5% 71.3% 100.0%PPV 0.0% 0.0% 0.0% NPV 100.0% 78.6% 100.0%

QuReVeTeSaStBlDetesExNA 
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Statistical tests used:None Blinding:

“Treatment rationale was not always available to the sonographers.” Definition of positive and negative on screening test:Unilateral, no septations or solid components, diameter ≤ 5 cm, no ascites Length of followup: 

Mean 29 months (range 10-73 months) Type of followup:Repeat transabdominal US Followup interval:3-6 months 
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Kurjak, Shalan, Kupesic, et al., 1994 #4470 

Geographical location: Zagreb, Croatia Dates:Jan 1988-Dec 1992 Size of population:5013 in initial screening population 404 had simple cysts; results only reported for 88 with 2nd scan 

Screening studyReference standard:

Surgery or followup Reference standard applied to all test negatives?: Yes

Test reliability established?: Not referenced Statistical tests used:None Blinding: No

Definition of positive and negative on screening test:Cyst diameter ≥ 2.5 cm, < 5 cm , with resistance index ≥0.41 Length of followup: 

6 months Type of followup:

Age:NR for group with cyst Menopausal status (n [%]):Pre (< 45): 280 (69.3%) Peri (45-55): 0 Post (> 55): 124 (30.6%) Race/ethnicity (n [%]):NR Risk factors (n [%]):NR Inclusion criteria:40 years or older, absence of symptoms Exclusion criteria:NR Loss to followup:NR; apparently 0 

Symptomatic (n [%]):

0 Detected by exam (n [%]):NR Detected by imaging (n [%]):NR Combination (n [%]):

NR Additional data used for diagnosis:NR 

Monitoring test:Repeat ultrasound Interval of testing:6 months Definition of change:Not explicitly defined 

1) Cancer during followup after initial benign: 

 Dis+ Dis- Tot T+ 1 17 18 

T- 0 69 69 Tot 1 86 87  Lower Upper  Value 95% CI 95% CI Se 100.0% 0.0% 100.0%Sp 80.2% 71.8% 88.6% PPV 5.6% 0.0% 16.1% NPV 100.0% 95.7% 100.0%

Co--I31--SQuReVeTeSaStBlDetesExNA 
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Repeat ultrasound Followup interval:6 months 

Levine, Gosink, Wolf, et al., 1992 #10320 

Geographical location: Portland, OR Dates:Oct 1989-June 1990 Size of population:184; 32 had simple cysts at initial evaluation, 31 developed over course of study Other: Cross-sectional, volunteer screening Reference standard:

Followup Reference standard applied to all test negatives?: YesTest reliability established?: Not discussed or referenced Statistical tests used:Chi-square, t-test Blinding: No

Definition of positive and negative on screening test:Simple cyst – 

Age:Mean (SD): 63.6 (8.1) Range: 50-85 Menopausal status (n [%]):Post (> 55): 184 (100%) Race/ethnicity (n [%]):NR Risk factors (n [%]):NR Inclusion criteria:Age ≥ 59, 

postmenopausal at least 1 year Exclusion criteria:NR Loss to followup:49 of 63 women with cysts had ultrasound followup (22.2% loss to followup) 

Symptomatic (n [%]):0 Detected by exam (n [%]):NR Detected by imaging (n [%]):

NR Combination (n [%]):NR Additional data used for diagnosis:NR 

Monitoring test:Transabdominal/ transvaginal ultrasound Doppler and CA-125 if abnormal Interval of testing:3 months Definition of change:Increased: diameter change ≥ 3 mm Decreased: diameter change ≤ 3 mm 

1) Cancer in simple cysts: 

 Dis+ Dis- Tot T+ 0 0 0 

T- 0 32 32 Tot 0 32 32  Lower Upper  Value 95% CI 95% CI Se - - - Sp 100.0% 90.6% 100.0%PPV - - - NPV 100.0% 90.6% 100.0%

Co--R--IQuReVeTeSaStBlDetesExNA 
D-306

Evidence Table 5 (continued) 

Study Study Design Patients Clinical 

Presentation 

Monitoring Strategy Results Co

Sc

completely anechoic, unilocular, nonseptated Length of followup: 

2 years (“over half one year or more”) Type of followup:Transabdominal and transvaginal ultrasound Followup interval:3 months x 1 year, then every 6 months 

Maggino, Gadducci, D’Addario, et al., 1994 #4500 

Geographical location: Padua, Pisa, Bari, Brescia, and Milan, Italy Dates:Mar 1991-Mar 1992 Size of population:335; 45 with benign cyst and CA-125 < 35 Case series Reference standard:

Surgery or followup Reference standard applied to all test negatives?: YesTest reliability established?: Yes

Statistical tests used: Se, Sp, PPV, NPV, Kappa 

Age:NR for subgroup of interest Menopausal status (n [%]):Post (> 55): 45 (100%) Race/ethnicity (n [%]):NR Risk factors (n [%]):

NR Inclusion criteria:Pelvic mass, at least 1 year postmenopausal Exclusion criteria:Incomplete US data, no CA-125, no histology for patients with surgery Loss to followup:

Symptomatic (n [%]):NR Detected by exam (n [%]):NR Detected by imaging (n [%]):NR Combination (n [%]):NR Additional data used for diagnosis:NR 

Monitoring test:Not systematic Interval of testing:NR Definition of change:NR 

1) Cancer during followup after initial benign: 

 Dis+ Dis- Tot T+ 0 0 0 

T- 0 45 45 Tot 0 45 45  Lower Upper  Value 95% CI 95% CI Se - - - Sp 100.0% 93.3% 100.0%PPV - - - NPV 100.0% 93.3% 100.0%

Co--Nstr--NfolQuReVeTeSaStBlDetesExNA 
D-307

Evidence Table 5 (continued) 

Study Study Design Patients Clinical 

Presentation 

Monitoring Strategy Results Co

Sc

Blinding: No

Definition of positive and negative on screening test:< 5 cm, thin wall, no echoes, ≤ 3 thin septa, 

no free fluid in pelvis Length of followup: 

NR Type of followup:NR Followup interval:NR 

2/45 (4.4%) 

Menon, Talaat, Rosenthal, et al., 2000 #2780 

Geographical location: United Kingdom Dates:1986-1989 Size of population:22,000 screened; 741 with elevated CA125 had US; 97 scans were abnormal or equivocal Screening study Reference standard:

Pathology and clinical followup Reference standard applied to all test negatives?: No

Test reliability established?: ?

Age:NR Menopausal status (n [%]):All older than 45 (22,000/100%) Race/ethnicity (n [%]):NRRisk factors (n [%]):

NR Inclusion criteria:Age > 45, CA-125 > 30 on screening Exclusion criteria:Premenopausal, CA125 < 30 Loss to followup:

NR 

Symptomatic (n [%]):NR Detected by exam (n [%]):NR Detected by imaging (n [%]):NR Combination (n [%]):NR Additional data used for diagnosis:NR 

Monitoring test:Pelvic ultrasound/serial CA-125 Interval of testing:Depends on findings. If equivocal US, repeat every 6 weeks until normal or abnormal. If normal, repeat the CA125 every 3 months for a year. If US abnormal, 

refer to gynecologist for a decision. Definition of nl or abnl:Normal: volume < 8.8 ml or ovaries not visualized Equivocal: volume < 8.8 with abnormal morphology Abnormal: volume > 

Among 17 patients with an equivocal scan who were triaged to followup in 4-6 weeks: -9 had simple cysts, did not have surgery, and did not develop cancer (true negatives); -1 died of ovarian cancer before her repeat ultrasound (can’t categorize); -1 died of pneumonia before a repeat ultrasound could be done (can’t categorize); -5 had surgery with benign pathology found (number of followup scans not specified; all false positives); -1 had surgery with ovarian cancer found (true positive). 

Co--Qwi

be

thidifbe(caabsucathois an--Mbufol--AhanodeQuReVefol
D-308

Evidence Table 5 (continued) 

Study Study Design Patients Clinical 

Presentation 

Monitoring Strategy Results Co

Sc

Statistical tests used:Blinding: NoDefinition of positive and negative on screening test:Yes Length of followup: 

Median 6.8 years Type of followup:Annual questionnaires, Tumor Registry, pathology Followup interval:

If scan normal, repeat CA-125 every 3 months for a year. If scan equivocal, repeat every 6 weeks until it can be classified as normal or abnormal. If scan abnormal, refer to gynecologist – surgical intervention at the gynecologist’s discretion.

8.8 irrespective of morphology 

all TeSaStBlDetesEx
D-309

Evidence Table 5 (continued) 

Study Study Design Patients Clinical 

Presentation 

Monitoring Strategy Results Co

Sc

Modesitt, Pavlik, Ueland, et al., 2003 #5560 

Geographical location: Lexington, KY Dates:1987-2002 Size of population:15,106 screened with TVUS; 2763 women had 3259 unilocular ovarian cysts Screening study Reference standard:

Clinical followup (mean 6.3 years) Reference standard applied to all test negatives?: YesTest reliability established?: Yes

Statistical tests used:Blinding:

Definition of positive and negative on screening test:Negative: unilocular simple cyst Positive: any septum, solid area, papillary projections, or volume > 10 cm3

Length of followup: 

6.3 years Type of followup:

Age:NR Menopausal status (n [%]):Post (> 55): 100% Race/ethnicity (n [%]):

NR Risk factors (n [%]):

49% of patients with unilocular cysts were on hormone replacement therapy Inclusion criteria:At least 50 years old Exclusion criteria:Known ovarian tumor prior to screening, previous diagnosis of ovarian cancer, symptoms consistent with a pelvic mass Loss to followup:

NR; mean followup 6.3 years 

Symptomatic (n [%]):0 Detected by exam (n [%]):0 Detected by imaging (n [%]):2763 (100%) Combination (n [%]):0 Additional data used for diagnosis:NR 

Monitoring test:TVUS Interval of testing:Repeat in 4-6 weeks with Doppler and CA125 if abnormality detected. A tumor score from 0-10 was assigned based on volume and structure at the second scan. If cyst still appears simple at second scan, repeat TVUS every 3-6 months. Definition of change:Development of a septum or solid area, volume >10 cm3, 

papillary projections into cyst 

2763 women had 3259 unilocular cysts. Of these, 2261 (69.4%) spontaneously resolved, 220 (6.8%) persisted, 726 (22.3%) developed changes such as septa or solid areas and were no longer considered simple, 12 (0.3%) had an ovary that couldn’t be visualized on a subsequent scan, and 40 (1.2%) were removed during a subsequent surgery. Authors did not report how many patients had surgery. They did report that 10 patients in this “unilocular cyst” population subsequently developed ovarian cancer:

-7 of these had an additional abnormal area that developed on their TVUS besides the simple cyst (so presumably they are not “false negatives”-they were caught by screening eventually). -2 had the cyst in question resolve spontaneously, but were ultimately diagnosed with ovarian cancer (should these be considered false negatives – probably not). -1 was ultimately diagnosed with cancer in the opposite ovary (probably not a false negative). They therefore claim a 0% false negative rate in unilocular cysts < 10 cm (none of these cysts subsequently turned into cancer). If all 3 in question above are treated as false negatives, the 2x2 table is below: (“by patient,” not “by cyst”) 

 Dis+ Dis- Tot T+ 7 0 7 

T- 3 2753 2756 Tot 10 2753 2763 

Co--Govrefol--Cpashnedeorthe for QuReVefoTeSaStBlDetesEx
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Evidence Table 5 (continued) 

Study Study Design Patients Clinical 

Presentation 

Monitoring Strategy Results Co

Sc

Followup interval:

 Lower Upper  Value 95% CI 95% CI Se 70.0% 41.6% 98.4% Sp 100.0% 99.9% 100.0%PPV 100.0% 57.1% 100.0%NPV 99.9% 99.8% 100.0%

2) On a “by cyst” basis, there are no false negatives, since the 3 patients who had cancers did so after the cysts in question resolved (or in the opposite ovary): 

 Dis+ Dis- Tot T+ 7 0 7 T- 0 3252 3252 Tot 7 3252 3259  Lower Upper  Value 95% CI 95% CI Se 100.0% 57.1% 100.0%Sp 100.0% 99.9% 100.0%PPV 100.0% 57.1% 100.0%NPV 100.0% 99.9% 100.0%
D-311

Evidence Table 5 (continued) 

Study Study Design Patients Clinical 

Presentation 

Monitoring Strategy Results Co

Sc

Schincaglia, Brondelli, Cicognani, et al., 1994 #4520 

Geographical location: Bologna, Italy Dates:Aug 1988-Jun 1992 Size of population:-3541 screened -347 were asked to followup, and can be split into 2 groups: 

-249 were followed 

with additional scans but not deemed “abnormal” enough to refer for FNA/surgery  -98 were referred for possible FNA (“abnormal”) -2 cancers diagnosed in the 98 who were referred -no cancers among the rest of the population (maximum followup was 1 year) Screening study Reference standard:

Pathology and clinical followup up to 1 year Reference standard applied to all test negatives?: Yes

Test reliability established?: NoStatistical tests used:SP, PPV 

Age:NR Menopausal status (n [%]):Post (> 55): 3541 (100%) Race/ethnicity (n [%]):NR Risk factors (n [%]):NR Inclusion criteria:Postmenopausal, no prior pelvic surgery or pelvic symptoms Exclusion criteria:Prior pelvic surgery, pelvic symptoms Loss to followup:

Not stated, but followup listed as “at least one year” for negative screens and those managed conservatively 

Symptomatic (n [%]):0 Detected by exam (n [%]):0 Detected by 

imaging (n [%]):All who qualified for followup (347) Combination (n [%]):NR Additional data used for diagnosis:NR 

Monitoring test:Ultrasound Interval of testing:See below Definition of change:See below Volume of ovaries: < 9 negative < 9 with a cyst: followup US in 6 months. Increased volume Æ refer to level II 9-15: followup 3 and 6 months. Unchanged Æ

refer to level II > 15 referral to level II Level II: Morphology assessment and biopsy if feasible Surgery if FNA not feasible, inadequate, positive, or patient refuses FNA 

1) Of the 347 patients selected for followup initially, 283 were deemed appropriate for followup using repeat ultrasound at 3- to 6-month intervals without immediate referral for FNA/surgery. Of these 283, 34 subsequently had concerning US results and were referred for level II scan and possible FNA. The results of this group of 34 are not given separately. Of the 249 who had nonconcerning followup scans, none developed cancer, with followup of ”at least” 1 year. Therefore Specificity is 100% for patients with an initial abnormal but “probably benign” finding who had reassuring followup studies. Sensitivity within this group cannot be calculated with the information given. 

 Dis+ Dis- Tot T+ 2 96 98 

T- 0 249 249 Tot 2 345 347  Lower Upper  Value 95% CI 95% CI Se 100.0% 0.0% 100.0%Sp 72.2% 67.4% 76.9% PPV 2.0% 0.0% 4.8% NPV 100.0% 98.8% 100.0%

Co--Tbehepaabsc--Anonodethe milarQuReVenoTeSaStBlDetesEx
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Evidence Table 5 (continued) 

Study Study Design Patients Clinical 

Presentation 

Monitoring Strategy Results Co

Sc

Blinding: NRDefinition of positive and negative on screening test:See under “Monitoring Strategy”Length of followup: 

At least 1 year Type of followup:Questionnaire for negative screens; others had followup studies as specified under “Monitoring Strategy” Followup interval:Varied by ultrasound findings

Valentin and 

Akrawi, 2002 #8490 

Geographical location: Malmo, Sweden Dates:June 1991-Nov 2000 Size of population:162; 134 agreed to followup (28 not followed older, had higher mortality) Consecutive caseseries Reference standard:Surgery or followup Reference standard applied to all test 

Age:Median: 61 Range: 47-87 Menopausal status (n [%]):Post (> 55): 134 (100%) Race/ethnicity (n [%]):NR Risk factors (n [%]):NR Inclusion criteria:Cysts “judged to be benign,” age ≥ 40, menopausal for at least 1 year 

Symptomatic (n [%]):84 (62.7%) Detected by exam (n [%]):NR Detected by imaging (n [%]):

NR Combination (n [%]):NR Additional data used for diagnosis:NR 

Monitoring test:TVUS Interval of testing:3, 6, 12, then every 12 months Definition of change:Positive difference between largest diameter at most recent examination and at initial examination, or cyst “more complex” Morphology improved if cyst complexity decreased 

1) Change in US as positive test, cancer as disease: 

 Dis+ Dis- Tot T+ 0 7 7 

T- 0 127 127 Tot 0 134 134  Lower Upper  Value 95% CI 95% CI Se Sp 94.8% 91.0% 98.5% PPV 0.0% 0.0% 0.0% NPV 100.0% 97.6% 100.0%

4 additional patients were operated on for other causes 

Co--CQuReVeTeSaStBlDetesrefExNA 
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Evidence Table 5 (continued) 

Study Study Design Patients Clinical 

Presentation 

Monitoring Strategy Results Co

Sc

negatives?: YesTest reliability established?: Yes

Statistical tests used:Sp, PPV, NPV Blinding: No

Definition of positive and negative on screening test:Referenced but not explicitly described in this paper Length of followup: 

Median 3 years (range 4 months-8 years) Type of followup:Transvaginal ultrasound Followup interval:3, 6, 12 months, then every 12 months 

Exclusion criteria:NR Loss to followup:0% (mortality and surgical data obtained from Swedish national registries) 
D-314

Evidence Table 6: Question 6: Among women with adnexal masses, what are the morbidity and mortality from diagnostic surgery (la

laparotomy)? At what point does the risk of surgery outweigh the risk of detecting malignancy?

Study Study Design Patients Clinical Presentation Results Comm

Canis, Mage, Pouly, et al., 1994 #4610 

Geographical location: Clermont-Ferrand, France Dates: NR Size of population:757 Registry Morbidity definitions:

Not described Length of followup after surgery:Mean 42 months (range 3-153) 

Age:Mean (SD): 35.8 (12.6) Range: 8-84 Menopausal status (n [%]):Pre (< 45): 671 (88.6%) Post (> 55): 86 (11.4%) 92 patients > 50 Race/ethnicity (n [%]):NR Risk factors (n [%]):NR Loss to followup:

81/620 (13.1%) 

Symptomatic (n [%]):NR Detected by exam (n [%]):NR Detected by imaging (n [%]):NR Combination (n [%]):NR Additional data used for diagnosis:Ultrasound Age CA-125 “Recurrent cysts” < endometriomas, paraovarian and functional cysts, pseudoperitoneal cysts, and hydrosalpinges excluded; not clear if excluded before or after surgical diagnosis 

1) Mortality: 0/757 (95% CI, 0 to 0.6%) 2) Morbidity (total all complications): 8/727 (1.1%) 3) Specific complications: 1 gastric laceration 1 acute abdomen 1 peritonitis (sigmoid laceration) 2 ovarian abscess 2 peritonitis (ruptured teratoma)  1 led to immediate re-operation  1 led to operation for CPP 12 mo later 1 abdominal wall endometrioma  re-operated 4) Rate of conversion to laparotomy: Not described for non-malignant tumors 

Comme--Unclecases eQuality Size of sample NumbePatient Applica
D-315

Evidence Table 6 (continued) Study Study Design Patients Clinical Presentation Results CommCanis, Mashiach, Wattiez, et al., 2004 #7720 

Geographical location: Clermont-Ferrard, France Dates: ?1992-1997 (specific dates not given) Size of population:839 total , 141 with frozen section Single center Morbidity definitions:

Sensitivity/specificity of frozen section Length of followup after surgery:Up to 10 years (not uniformly) 

Age:Mean (SD): 43.6 (15.9) Menopausal status (n [%]):Pre (< 45): 99 (70.2%) Post (> 55): 42 (29.8%) Race/ethnicity (n [%]):NR Risk factors (n [%]):NR Loss to followup:

NR 

Symptomatic (n [%]):NR Detected by exam (n [%]):NR Detected by imaging (n [%]):NR Combination (n [%]):NR Additional data used for diagnosis:NR 

1) Mortality: NR 2) Morbidity (total all complications): Sensitivity/specificity of frozen section: Low malignant potential = cancer, “unclear” results on frozen = positive test 

 Dis+ Dis- Tot T+ 47 4 51 

T- 4 86 90 Tot 51 90 141  Lower Upper  Value 95% CI 95% CI Se 92.2% 84.8% 99.5% Sp 95.6% 91.3% 99.8% PPV 92.2% 84.8% 99.5% NPV 95.6% 91.3% 99.8% 

3) Specific complications: NR 4) Rate of conversion to laparotomy: NR 

Comme--ClinicadescribQuality Size of sample NumbePatient Applica

Carley, Klingele, Gebhart, et al., 2002 #8500 

Geographical location: Rochester, MN Dates: Dec 1995-Nov 2000 Size of population:106 Single center Morbidity definitions:

-Febrile morbidity -Transfusion -Conversion Length of followup after surgery:Not specified 

Age:Mean (SD): Laparotomy: 46.4 (13.5) Laparoscopy: 49.2 (15.9) Menopausal status (n [%]):NR Race/ethnicity (n [%]):NR Risk factors (n [%]):NR Loss to followup:

NR 

Symptomatic (n [%]):History not reported Detected by exam (n [%]):NR Detected by imaging (n [%]):NR Combination (n [%]):NR Additional data used for diagnosis:Masses > 7 cm or with CA125 > 35 not included in analysis; malignant pathology excluded 

1) Mortality: NR 2) Morbidity (total all complications): Laparotomy: 2/44 (4.6%; 95% CI, 0.7, 16.7%) 3) Specific complications: Transfusion: Laparotomy: 1/44 (2.3%; 95% CI, 0 to 13.5%) Laparoscopy (including conversions): 0/62 (0 to 8.6%) Febrile morbidity: Laparotomy: 1/44 (2.3%; 0 to 13.5%) Laparoscopy: 0/62 (0 to 8.6%) 4) Rate of conversion to laparotomy: 16% 

Quality Size of sample NumbePatient Applica
D-316

Evidence Table 6 (continued) Study Study Design Patients Clinical Presentation Results CommChapron, Dubuisson, and CapellaAllouc, 1997 #6150 

Geographical location: Paris, France Dates: Jan 1989-Dec 1994 Size of population:186 Single center Morbidity definitions:

-Conversion to laparotomy -Complications Length of followup after surgery:NR 

Age:Mean: Laparotomy 45.7 Laparoscopy 49.5 Range: Laparotomy 18-72 Laparoscopy 19-82 Menopausal status (n [%]):LaparotomyPre (< 40): 18 (27.7%) Peri (40-50): 28 (43.1%) Post (> 50): 19 (29.2%) LaparoscopyPre (< 40): 21 (18.2%) Peri (40-50): 38 (31.4%) Post (> 50): 61 (50.4%) Race/ethnicity (n [%]):NR Risk factors (n [%]):NR Loss to followup:

NR 

Symptomatic (n [%]):NR Detected by exam (n [%]):NR Detected by imaging (n [%]):NR Combination (n [%]):NR Additional data used for diagnosis:All patients underwent removal of adnexal Patients with “prophylactic” adnexal removal due to age, family history excluded 

1) Mortality: Laparotomy: 0/65 (95% CI, 0 to 8.3%) Laparoscopy: 0/121 (0 to 4.5%) 2) Morbidity (total all complications): Laparotomy: 10/65 (15.4%; 95% CI, 8.9 to 27.0%) Laparoscopy: 10/121 (8.3%; 4.6 to 15.0%) 3) Specific complications: Laparotomy: Cystitis: 2/65 Febrile morbidity: 2/65 

Abdominal wall hematoma: 1/65 Abdominal wall abscess: 2/65 Bowel obstruction: 1/65 Evisceration: 2/65 Laparoscopy: Urinary tract infection: 1/121 Febrile morbidity: 5/121 Bowel obstruction: 1/121 Evisceration: 2/121 (both re-operated) Sigmoid injury: 1/121 (re-operated) 4) Rate of conversion to laparotomy: 19/140 (13.6%; 95% CI, 9.0 to 20.6%) 

Comme--Groupbaselinhigher sto direclaparotosurgery hemope--Descrsurgery --19 of started provide“intentio--Reopenot men--Didn’t specific laparotoQuality Size of sample describNumbePatient Applica(all pati
D-317

Evidence Table 6 (continued) Study Study Design Patients Clinical Presentation Results CommChi, AbuRustum, Sonoda, et al., 2004 #7870 

Geographical location: New York, NY Dates: Jan 1991-Dec 2000 Size of population:1451 (146 with diagnostic laparoscopy) Single center Morbidity definitions:

-Grade 1: use of oral medications, bedside interventions -Grade 2: IV medications, TPN, enteral nutrition, or blood transfusion -Grade 3: interventional radiology, endoscopy, intubation, or operation -Grade 4: Residual and lasting disability that requires major rehabilitation or organ resection -Grade 5: Death Length of followup after surgery:30 days 

Age: (all patients) Median: 54 Range: (15-88) Menopausal status (n [%]):NR Race/ethnicity (n [%]):NR Risk factors (n [%]):NR Loss to followup:

NR 

Symptomatic (n [%]):Pre-procedure history not reported Detected by exam (n [%]):NR Detected by imaging (n [%]):NR Combination (n [%]):NR Additional data used for diagnosis:NR 

Results presented for diagnostic laparoscopy only 1) Mortality: 3/146 (2.5%; 95% CI, 0.5 to 6.3%) 2) Morbidity (total all complications): 19/146 (13.0%; 95% CI, 8.6 to 19.8%) 3) Specific complications: Grade 1: 14/146 (9.6%; 95% CI, 5.8 to 15.8%) 

Grade 2: 1/146 (0.7%; 0 to 4.3%) Grade 3: 4/146 (2.7%; 0.9 to 7.2%) Grade 4: 0/146 (0%; 0 to 3.76%) 4) Rate of conversion to laparotomy: 15/146 (10.3%; 95% CI, 6.4 to 16.6%) 5) Multivariate analysis: Complications significantly more likely with older age, history of radiation therapy, malignancy 

Comme--Gynec--Propomass (amalignaQuality Size of sample NumbePatient Applica
D-318

Evidence Table 6 (continued) Study Study Design Patients Clinical Presentation Results CommChilders, Nasseri, and Surwit, 1996 #6940 

Geographical location: Tucson, AZ Dates: July 1991-Jan 1995 Size of population:138 Single center Morbidity definitions:

Complications Length of followup after surgery:23-50 months (mean 37) in patients with malignancy; not given for others 

Age:Mean: 52 Range: 9-91 Menopausal status (n [%]):NR Race/ethnicity (n [%]):NR Risk factors (n [%]):NR Loss to followup:

NR 

Symptomatic (n [%]):NR Detected by exam (n [%]):NR Detected by imaging (n [%]):NR Combination (n [%]):NR Additional data used for diagnosis:“Suspicious adnexal mass”, which on ultrasound did not meet all criteria: --Size < 10 cm --Unilateral --Smooth borders --No excrescences --No solid parts --No fluid in cul-de-sac, and with no ascites, malignant cells on paracentesis, or upper abdominal masses 

1) Mortality: 0/138 (95% CI, 0 to 4.0%) 2) Morbidity (total all complications): 14/138 (10.1%; 95% CI, 6.2 to 16.7%) 3) Specific complications: Enterotomy: 1/138 Vena Cava injury: 1/138 Bowel herniation: 1/138 (re-operated) Febrile morbidity: 2/138 Ileus: 3/138 Cardiac arrhythmia: 4/138 Urinary retention: 2/138 4) Rate of conversion to laparotomy: 11/138 (8.0%; 95% CI, 4.5 to 14.1%) All for either technical reasons, debulking, or staging; none for complications 

5) Malignancy 19/138 (13.8%; 95% CI, 9.1 to 20.9%) 

Comme--Selecgynecohigher p--No dapresent--ResulmenopaQuality Size of sample base) NumbePatient many plaparosApplica(all und
D-319

Evidence Table 6 (continued) Study Study Design Patients Clinical Presentation Results CommDeckardt, Saks, and Graeff, 1994 #4310 

Geographical location: Munich, Germany Dates: NR Size of population:192 Single center randomized trial Morbidity definitions:

Complications Length of followup after surgery:NR 

Age:Laparotomy: Mean: 43.6 Range: 20-84 Laparoscopy: Mean: 40.1 Range: 18-74 Menopausal status (n [%]):Laparotomy:Pre (< 45): 73.7% Post (> 55): 26.3% Laparoscopy:Pre (< 45): 77.6% Post (> 55): 22.4% Race/ethnicity (n [%]):NR Risk factors (n [%]):NR Loss to followup:

NR 

Symptomatic (n [%]):NR Detected by exam (n [%]):NR Detected by imaging (n [%]):NR Combination (n [%]):NR Additional data used for diagnosis:Premenopausal: mass > 6 cm, persistent after 6 months, symptomatic; infertility; not a corpus luteum cyst by ultrasound Postmenopausal: any adnexal mass Patients randomized according to ward where they were admitted 

1) Mortality: Laparotomy: 0/76 (95% CI, 0 to 7.1%) Laparoscopy: 0/116 (0 to 4.7%) 2) Morbidity (total all complications): Laparotomy: 23/76 (30.3%; 21.8 to 42.3%) Laparoscopy: 13/116 (11.2%; 6.8 to 18.7%)

3) Specific complications: Bladder injury: Laparotomy 1/76, laparoscopy 0/116 Incisional hernia: Laparotomy 3/76, laparoscopy 1/116 Umbilical hernia: Laparotomy 0/76, laparoscopy 1/116 UTI: Laparotomy 12/76, laparoscopy 2/116 Febrile morbidity: Laparotomy 3/76, laparoscopy 2/116 Bowel obstruction: Laparotomy 1/76, laparoscopy2/116 Chemical peritonitis: Laparotomy 0/76, laparoscopy 1/116 Small bowel injury: Laparotomy 2/76, laparoscopy 1/116 Pulmonary embolus: Laparotomy 1/76, laparoscopy 0/116 Wound dehiscence: Laparotomy 2/76, laparoscopy 1/116 4) Rate of conversion to laparotomy: 4/116 (3.5%; 1.2 to 9.0%) 5) 46% of laparotomy patients received prophylactic antibiotics, compared to 2.6% of laparoscopy patients 6) Laparoscopy patients significantly more likely to have cystectomy (60.0% vs 20.2%), less likely to have oophorectomy (0.8% vs 20.2%), less likely to have bilateral salphingo-oophorectomy (4.0 vs 21.4%) 7) Reoperation 1/76 for laparotomy (assume 0/116 for laparoscopy?) 

Comme--Randodifferencharactperformtreatme--No siggroups Quality Size of sample NumbePatient treatmeApplica
D-320

Evidence Table 6 (continued) Study Study Design Patients Clinical Presentation Results CommDottino, Levine, Ripley, et al., 1999 #6920 

Geographical location: New York, NY Dates: Apr 1992-Apr 1996 Size of population:160 Single center Morbidity definitions:

-Conversion to laparotomy -“Complications” -Reoperation -Misdiagnosis Length of followup after surgery:NR, but paper published Feb 1999, last patient enrolled Apr 1996 

Age:Mean (SD): 52.2 (13.1) Menopausal status (n [%]):Pre (< 45): 75 (47%) Post (> 55): 85 (53%) Race/ethnicity (n [%]):White: 146 (91%) Other: 34 (9%) Risk factors (n [%]):NR Loss to followup:

NR 

Symptomatic (n [%]):NR Detected by exam (n [%]):NR Detected by imaging (n [%]):NR Combination (n [%]):NR Additional data used for diagnosis:All patients undergoing laparoscopic evaluation of adnexal mass by gynecologic oncologist; excluded if mass above umbilicus, other indication for laparotomy, evidence of gross metastatic disease 

1) Mortality: 0/160 (95% CI, 0 to 3.4%) 2) Morbidity (total all complications): 12/160 (7.5%; 95% CI, 4.3 to 12.9%) 3) Specific complications: Vascular injury: 2/160 (1.3%; 95% CI, 0.9 to 4.8%) Bleeding: 1/160 (0.6%; 0 to 3.9%) Intra-op bowel injury: 1/160 (0.6%; 0 to 3.9%) Postop bowel obstruction: 3/160 (1.9%; 0.4 to 5.7%) Postop febrile morbidity:4/160 (2.5%; 0.8 to 6.6%) 

4) Rate of conversion to laparotomy: Total: 19/160 (11.9%; 95% CI, 7.8 to 18.1%)Secondary to complications: 5/160 (3.1%; 1.2 to 7.4%) 5) Final diagnoses Benign: 139 (87%; 95% CI, 84 to 90%) Borderline: 8 (5%; 2.5 to 9.9%) Ovarian cancer: 9 (5%; 2.9 to 10.6%)  4 of 9 epithelial cancers postmenopause Non-gynecological cancer: 4 (3%; 0.8 to 6.6%) 6) Other: 5 frozen sections reports changed from benign to borderline (3), malignant to benign (1), benign to cancer (1) 

Comme--Cases gynecosuggesterms oanticipaQuality Size of sample referral NumbePatient descriplikelihooApplica(all got 
D-321

Evidence Table 6 (continued) Study Study Design Patients Clinical Presentation Results CommFanfani, Fagotti, Ercoli, et al., 2004 #7810 

Geographical location: Rome, Italy Dates: Jan 2003-Aug 2003 Size of population:100 Single center randomized trialMorbidity definitions:

-Ileus -Fever (temperature ≥

38° C on 2 consecutive measurements at least 6 hours apart) -Anemia (hemoglobin < 8 g/dl) -Bowel/bladder/ureteral injuries Length of followup after surgery:30 days 

Age:Mean (SD): Laparoscopy: 36.3 (12.1) Laparotomy: 37.5 (13.4) Menopausal status (n [%]):Laparoscopy: 5 (10%) postmenopausal Laparotomy: 10 (20%) postmenopausal Race/ethnicity (n [%]):

NR Risk factors (n [%]):NR Loss to followup:0 

Symptomatic (n [%]):Laparoscopy: 35 (70%) Laparotomy: 38 (76%) Detected by exam (n [%]):NR Detected by imaging (n [%]):NR Combination (n [%]):NR Additional data used for diagnosis:Randomized trial Patients excluded for BMI > 32 Cysts > 12 cm Hysterectomy required Postmenopausal and CA125 > 35 

1) Mortality: 0 2) Morbidity (total all complications): Laparoscopy: 0/50 (0%; 95% CI, 0 to 10.6%) Laparotomy: 3/50 (6.0%; 1.8 to 17.5%) 3) Specific complications: Fever: Laparoscopy: 0 Laparotomy: 2 (4%; 95% CI, 0.6 to 14.8%) Anemia: Laparoscopy : 0 Laparotomy: 1 (2%; 0 to 12.0%) 4) Rate of conversion to laparotomy: 0 

Comme--No ma--Small Quality Size of sample NumbePatient Applica
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Evidence Table 6 (continued) Study Study Design Patients Clinical Presentation Results CommHavrilesky, Peterson, Dryden, et al., 2003 #8180 

Geographical location: Durham, NC Dates: NR Size of population:396 Single center Morbidity definitions:

-Estimated blood loss ≥

500 cc -Incision disruption/infection -Urinary retention -Small bowel obstruction -Urinary tract/GI/nerve injury -Subcutaneous emphysema -Hemorrhage -Transfusion -Readmission -Re-exploration Length of followup after surgery:NR 

Age:Median: 43 Range: 12-87 Menopausal status (n [%]):Pre (< 45): NR Peri (45-55): NR Post (> 55): 317 (37.2%) Race/ethnicity (n [%]):

White: 71.2% Black: 26.2% Other: 2.4% Risk factors (n [%]):NR Loss to followup:NR

Symptomatic (n [%]):Clinical history NR Detected by exam (n [%]):NR Detected by imaging (n [%]):NR Combination (n [%]):NR Additional data used for diagnosis:NR 

1) Mortality: 0 (95% CI, 0 to 1.2%) 2) Morbidity (total all complications): 33/396 (8.3%; 95% CI, 6.0 to 11.6%) 

3) Specific complications: Incisional disruption/infection: 7 (1.8%; 95% CI, 0.8 to 3.7%) Urinary retention: 3 (0.8%; 0.2 to 2.4%) Partial small bowel obstruction/prolonged ileus: 5 (1.3%; 0.5 to 3.1%) Urinary tract injury: 1 (0.25%; 0 to 1.6%) Bowel injury: 2 (0.5%; 0.03 to 2.0%) Nerve injury: 1 (0.25%; 0 to 1.6%) Hemorrhage: 7 (1.8%; 0.8 to 3.7%) Re-exploration: 5 (1.3%; 0.5 to 3.1%) 4) Rate of conversion to laparotomy: 25% 5) Undiagnosed cancer: 8/396 (2.0%) 

Comme--Presu--Risk owith co--Risk ohistory --8/396 borderlQuality Size of sample NumbePatient Applica
D-323

Evidence Table 6 (continued) Study Study Design Patients Clinical Presentation Results CommHidlebaugh, Vulgaropulos, and Orr, 1997 #9490 

Geographical location: Worcester, MA Dates: Jan 1988-Dec 1995 Size of population:405 Single center Morbidity definitions:

-Fever -Ilieus -Anemia/transfusion -Wound infection -Deep vein thrombosis -Reoperation -Readmission Length of followup after surgery:NR 

Age:Range: 14-83 Menopausal status (n [%]):Pre (< 45): NR Peri (45-55): NR Post (> 55): 82 (20.2%) Race/ethnicity (n [%]):NR Risk factors (n [%]):NR Loss to followup:

NR 

Symptomatic (n [%]):NR Detected by exam (n [%]):NR Detected by imaging (n [%]):NR Combination (n [%]):NR Additional data used for diagnosis:NR 

1) Mortality: 0 (95% CI, 0 to 1.38%) 2) Morbidity (total all complications): Laparoscopy: 5/199 (2.5%; 95% CI, 1.0 to 6.0%) Laparotomy: 56/206 (27.2%; 21.8 to 34.0%)3) Specific complications: 

Intra-operative: Laparoscopy: 1/199 (0.5%; 95% CI, 0 to 3.2%) Laparotomy: 3/206 (1.5%; 0.3 to 4.5%) Postoperative: Laparoscopy: 2/199 (1.0%; 0.1 to 3.9%) Laparotomy: 33/206 (16.0%; 11.8 to 21.9%)Late: Laparoscopy: 2/199 (1.0%; 0.1 to 3.9%) Laparotomy: 18/206 (8.7%; 5.6 to 13.6%) Readmission: Laparoscopy: 0/199 (0%; 0 to 2.4%) Laparotomy: 2/206 (1.0%; 0.1 to 3.8%) 4) Rate of conversion to laparotomy: 10/199 (5.0%; 95% CI, 2.7 to 9.2%) 

Comme--Selecvs. lapa--Potenfactors describ--ClinicaQuality Size of sample NumbePatient Applica
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Evidence Table 6 (continued) Study Study Design Patients Clinical Presentation Results CommLok, Sahota, Rogers, et al., 2000 #8890 

Geographical location: Hong Kong, China Dates: NR Size of population:513 Single center Morbidity definitions:

-Transfusion -Fever -Small bowel hernia -Pelvic hematoma -Urinary retention -Bowel/ureter/vascular injury -Reoperation Length of followup after surgery:NR

Age:Mean (SD): 35.6 (9.8) Menopausal status (n [%]):Pre (< 45): NR Peri (45-55): NR Post (> 55): 28 (5.5%) Race/ethnicity (n [%]):NR; presumably Asian Risk factors (n [%]):NR Loss to followup:NR

Symptomatic (n [%]):389 (75.8%) Detected by exam (n [%]):NR Detected by imaging (n [%]):NR Combination (n [%]):NR Additional data used for diagnosis:“Concurrent problems necessitating other major laparoscopic procedures” excluded 

1) Mortality: 0/513 (95% CI, 0 to 1.1%) 2) Morbidity (total all complications): 68/513 (13.3%; 95% CI, 10.6 to 16.6%) 3) Specific complications: Transfusion: 0 (95% CI, 0 to 1.1%) Intra-operative: 16/513 (3.1%; 1.9 to 5.1%) Postoperative: 44 (8.6%; 6.5 to 11.4%) Febrile morbidity: 20/513 (3.9%; 2.5 to 6.0%) Reoperation: 7/513 (1.4%; 0.6 to 2.9%) 4) Rate of conversion to laparotomy: 5 (0.97%; 95% CI, 0.4 to 2.4%) 5) Undiagnosed cancer: 2/513 (0.4%) 

Comme--Preopin detai--Preva--Criterlaparosdescrib

Quality Size of sample NumbePatient Applica

Mann and Reich, 1992 #10330 

Geographical location: Kingston, PA Dates: NR Size of population:44 Single center Morbidity definitions:

Readmission Length of followup after surgery:NR 

Age:Mean: 58.7 Range: 44-90 Menopausal status (n [%]):Post (> 55): 44 (100%) Race/ethnicity (n [%]):NR Risk factors (n [%]):NR Loss to followup:

NR 

Symptomatic (n [%]):7 (15.9%) Detected by exam (n [%]):NR Detected by imaging (n [%]):NR Combination (n [%]):37 (84.0%); proportion detected by exam vs imaging not reported Additional data used for diagnosis:NR 

1) Mortality: 0/44 (95% CI, 0 to 11.9%) 2) Morbidity (total all complications): 2/44 (4.6%; 95% CI, 0.7 to 16.7%) 3) Specific complications: Readmission: 2/44 (4.6%; 95% CI, 0.7 to 16.7%) 4) Rate of conversion to laparotomy: 2/44 (4.6%; 95% CI, 0.7 to 16.7%) 5) Undiagnosed cancer: 1/44 (2.3%) 

Comme--1/44 h--AsciteQuality Size of sample NumbePatient Applica
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Evidence Table 6 (continued) Study Study Design Patients Clinical Presentation Results CommMarana, Muzii, Catalano, et al., 2004 #5450 

Geographical location: Rome, Italy Dates: Jul 1990 - Dec 2001 Size of population:683 Two centers (same surgeon) Morbidity definitions:

-Complications -Recurrence Length of followup after surgery:Mean 30.2 months (minimum 6 months) 

Age:Mean: 27.6 Range: 12-39 Menopausal status (n [%]):Pre (< 45): 100% Race/ethnicity (n [%]):NR Risk factors (n [%]):NR Loss to followup:

NR 

Symptomatic (n [%]):416 (60.9%) Chronic pain: 147 (21.5%) Dysmenorrhea: 145 (21.2%)Infertility: 66 (9.7%) Menstrual irregularity: 57 (8.3%) Abdominal swelling: 1 (0.2%) Detected by exam (n [%]):267 (39.1%) (“routine”) Detected by imaging (n [%]):Not clear which of symptomatic ones were initially detected by imaging or exam Combination (n [%]):NR Additional data used for diagnosis:No solid components, papillation, or septae; if mass < 7 cm, ultrasound repeated in 8-12 weeks; CA-125 not done Age < 40 

1) Mortality: 0/683 (95% CI, 0 to 0.82%) 2) Morbidity (total all complications): 6/683 (0.9%; 95% CI, 0.4 to 2.0%) 3) Specific complications: Retrouterine hematoma: 3/683 Febrile morbidity: 2/683 Ileus: 1/683 Umbilical hernia: 1/683 Transfusion: 1/683 4) Rate of conversion to laparotomy: 16/683 (2.3%; 95% CI, 1.3 to 3.8%) 13 patients with advanced endometriosis, 2 

with large dermoids, one (0.15%) suspected malignancy (final pathology borderline) 5) 8 patients total with final path not benign – 7 borderline, 1 focal invasive endometrioid cancer 

Comme--Fairly importa--Limitewomen--Lapar0/116 Quality Size of sample describNumbePatient Applica
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Evidence Table 6 (continued) Study Study Design Patients Clinical Presentation Results CommParker, Levine, Howard, et al., 1994 #910 

Geographical location: Santa Monica, Irvine, and Los Angeles, CA; Louisville, KY; Rochester, NY Dates: NR Size of population:61 MulticenterMorbidity definitions:

-Complications -Conversion to laparotomy Length of followup after surgery:NR 

Age:Mean: 65 Range: 47-81 Menopausal status (n [%]):Post (> 55): 61 (100%) postmenopausal (> 45 with 12 months of amenorrhea, or FSH > 40 mIU/mL) Race/ethnicity (n [%]):NR Risk factors (n [%]):NR Loss to followup:

NR 

Symptomatic (n [%]):NR Detected by exam (n [%]):NR Detected by imaging (n [%]):NR Combination (n [%]):NR Additional data used for diagnosis:Ultrasound done in all; masses < 10 cm, cystic, no irregularities, solid components, septae > 2 mm, no ascites = “presumptively benign” Post menopause = > 45 years old with at least 12 months amenorrhea, if prior hysterecotomy = FSH > 40 

1) Mortality: 0/61(95% CI, 0 to 7.4%) 2) Morbidity (total all complications): 2/61 (3.3%; 95% CI, 0.4 to 12.3%) 3) Specific complications: Bladder perforation: 1/61 Sigmoid injury: 1/61 (led to laparotomy) 4) Rate of conversion to laparotomy: 3/61 (4.9%; 95% CI, 1.4 to 14.5%) 

Comme--Initial --“Presuform se--Only ireportesurgery short or Quality Size of sample describNumbePatient Applica

(laparot0/116)

Parker and Proietto, 1997 #9440 

Geographical location: Newcastle, Australia Dates: Jan 1993-Dec 1995 Size of population:86 Single center Morbidity definitions:

-Infection -Hernia -Pulmonary embolus -Wound hematoma or 

Age:Mean: 34.4 Range: 12-82 Menopausal status (n [%]):NR Race/ethnicity (n [%]):NR Risk factors (n [%]):NR Loss to followup:

NR 

Symptomatic (n [%]):NR Detected by exam (n [%]):NR Detected by imaging (n [%]):NR Combination (n [%]):NR Additional data used for diagnosis:NR 

1) Mortality: 0/86 (95% CI, 0 to 5.4%) 2) Morbidity (total all complications): 19/86 (22.1%; 95% CI, 15.1 to 32.7%) 3) Specific complications: Wound infection: 7/86 (8.1%; 95% CI, 4.0 to 16.5%) Other infection: 5/86 (5.8%; 2.4 to 13.5%) Other wound: 2/86 (2.3%; 0.2 to 8.5%) 4) Rate of conversion to laparotomy: NA (all laparotomies) 5) Undiagnosed cancer: 1/86 (1.2%) 

Quality Size of sample NumbePatient Applica
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Evidence Table 6 (continued) Study Study Design Patients Clinical Presentation Results Comm

other complication Length of followup after surgery:NR 

Sadik, Onoglu, Gokdeniz, et al., 1999 #2880 

Geographical location: Matalyta, Turkey Dates: NR Size of population:220 Single center registry

Morbidity definitions:

-Hospital stay -“Complications” Length of followup after surgery:NR 

Age:Mean (SD): 30.0 (9.7) Range: 13-68 Menopausal status (n [%]):Pre (< 45): 213 (96.8%) Post (> 55): 7 (3.2%) Race/ethnicity (n [%]):NR Risk factors (n [%]):NR Loss to followup:

NR Other: 66.9% no prior surgery 

Symptomatic (n [%]):NR Detected by exam (n [%]):NR Detected by imaging (n [%]):NR Combination (n [%]):NR Additional data used for diagnosis:Cystic adnexal mass > 5, < 10 cm, no irregular solid parts or septae > 2mm CA-125 < 35 No ascites, matted bowel No contraindication to surgery 

1) Mortality: 0/220 2) Morbidity (total all complications): 2/220 (0.9%) 3) Specific complications: Acute abdominal pain on postoperative day 5 – no cause at laparotomy Sigmoid perforation 4) Rate of conversion to laparotomy: Malignant masses “excluded from study” 5) 1 malignant dysgerminoma, 1 borderline serous cystadoma 6) 146 (67.3%) ruptured masses 

Comme--Data olaparoto--FollowQuality Size of sample NumbePatient Applica
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Evidence Table 6 (continued) Study Study Design Patients Clinical Presentation Results CommSerur, Emeney, and Byrne, 2001 #8700 

Geographical location: Brooklyn, NY Dates: Mar 1996-Nov 1998 Size of population:100 (19 converted to laparotomy) Single center Morbidity definitions:

-Pneumothorax -Wound infection -Fever -Enterotomy -Pneumonia Length of followup after surgery:Variable: 6 weeks for all All masses except patients with complex masses, ascites, and “elevated” CA-125 

Age:Range: 17-80 (Means not given for entire group) Menopausal status (n [%]):Pre (< 45): 51 (51%) Post (> 55): 49 (49%) Race/ethnicity (n [%]):NR Risk factors (n [%]):NR Loss to followup:

1/100 (1%) 

Symptomatic (n [%]):NR Detected by exam (n [%]):NR Detected by imaging (n [%]):NR Combination (n [%]):NR Additional data used for diagnosis:NR 

1) Mortality: 0/100 (0%; 95% CI, 0 to 5.44%) 2) Morbidity (total all complications): 10/100 (10%; 95% CI, 5.6 to 19.0%) 3) Specific complications: NR 4) Rate of conversion to laparotomy: 

19/100 (19%; 95% CI, 12.8 to 38.6%) 

Quality Size of sample NumbePatient Applica
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Evidence Table 6 (continued) Study Study Design Patients Clinical Presentation Results CommShalev, Eliyahu, Peleg, et al., 1994 #10140 

Geographical location: Afula, Israel Dates: May 1988-June 1993 Size of population:204; 55 underwent laparoscopy Single center Morbidity definitions:

-Fever -Pain (prolonged hospitalization) Length of followup after surgery:NR 

Age:NR Menopausal status (n [%]):Post (> 55): 204 (100%) Race/ethnicity (n [%]):NR Risk factors (n [%]):NR Loss to followup:

NR 

Symptomatic (n [%]):NR Detected by exam (n [%]):NR Detected by imaging (n [%]):NR Combination (n [%]):NR Additional data used for diagnosis:Inclusion: Simple or septate unilateral mass, CA-125 < 35

1) Mortality: 0/55 (95% CI, 0 to 9.6%) 2) Morbidity (total all complications): 6/55 (10.9%; 95% CI, 5.2 to 22.9%) 3) Specific complications: “Fever or pain” – not specified further 4) Rate of conversion to laparotomy: 0/55 (95% CI, 0 to 9.6%) 

Comme--PreopQuality Size of sample NumbePatient Applica

Somigliana, Ragni, Benedetti, et al., 2003 #8140 

Geographical location: Milan, Italy Dates: Jan 2001-Dec 2002 Size of population:32 Single center Morbidity definitions:

Number of follicles in response to ovarian stimulation after removal of endometriotic cyst Length of followup after surgery:Mean 2.4 (± 1.7) years 

Age:Mean (SD): 32.2 (3.7) Menopausal status (n [%]):Pre (< 45): 32 (100%) Race/ethnicity (n [%]):NR Risk factors (n [%]):NR Loss to followup:

NR 

Symptomatic (n [%]):NR Detected by exam (n [%]):NR Detected by imaging (n [%]):NR Combination (n [%]):NR Additional data used for diagnosis:NR 

1) Mortality: NR 2) Morbidity (total all complications): Number of follicles after stimulation significantly lower in ovary where cyst removed (2.0 ± 1.5) compared to other ovary (4.2 ± 2.5) 3) Specific complications: NR 4) Rate of conversion to laparotomy: NR 

Quality Size of sample NumbePatient Applica
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Evidence Table 6 (continued) Study Study Design Patients Clinical Presentation Results CommTangjitgamol, Jesadapatrakul, Manusirivithaya, et al., 2004 #1570 

Geographical location: Bangkok, Thailand Dates: Jan 1992-Dec 2002 Size of population:212 Single center Morbidity definitions:

Sensitivity/specificity of frozen section Length of followup after surgery:NR

Age:Mean (SD): 45.9 (17.1) Range: 13-89 Menopausal status (n [%]):NR Race/ethnicity (n [%]):NR Risk factors (n [%]):NR Loss to followup:

NA 

Symptomatic (n [%]):NR Detected by exam (n [%]):NR Detected by imaging (n [%]):NR Combination (n [%]):NR Additional data used for diagnosis:NR 

1) Mortality: NR 2) Morbidity (total all complications): “Defer” or greater = positive test, borderline = malignant 

 Dis+ Dis- Tot T+ 84 8 92 

T- 8 112 120 Tot 92 120 212  Lower Upper  Value 95% CI 95% CI Se 91.3% 85.5% 97.1% Sp 93.3% 88.9% 97.8% PPV 91.3% 85.5% 97.1% NPV 93.3% 88.9% 97.8% 

“Defer” or greater = positive test, borderline = benign 

 Dis+ Dis- Tot T+ 66 9 75 T- 10 127 137 Tot 76 136 212  Lower Upper  Value 95% CI 95% CI Se 86.8% 79.2% 94.4% Sp 93.4% 89.2% 97.6% PPV 88.0% 80.6% 95.4% NPV 92.7% 88.3% 97.1% 

3) Specific complications: NR 4) Rate of conversion to laparotomy: NR 

Comme--PresuQuality Size of sample NumbePatient Applica
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Evidence Table 6 (continued) Study Study Design Patients Clinical Presentation Results CommTarik and Fehmi, 2004 #7770 

Geographical location: Ankara, Turkey Dates: 1996-2003 Size of population:3572 (386 diagnostic laparoscopy, 1092 minor procedures) Single center Morbidity definitions:

-Vascular injury -Urinary tract injury -Bowel injury -Postoperative complications Length of followup after surgery:NR 

Age:Mean (SD): Diagnostic: 27.2 (4.6) Minor: 30.3 (3.2) Menopausal status (n [%]):NR Race/ethnicity (n [%]):NR Risk factors (n [%]):NR Loss to followup:

NR 

Symptomatic (n [%]):NR Detected by exam (n [%]):NR Detected by imaging (n [%]):NR Combination (n [%]):NR Additional data used for diagnosis:NR 

1) Mortality: 0/3572 (95% CI, 0 to 0.13%) 2) Morbidity (total all complications): Diagnostic: 7/386 (1.8%; 95% CI, 0.8 to 3.8%) Minor: 15/1092 (1.4%; 0.8 to 2.3%) 3) Specific complications: Vascular injury: Diagnostic: 4/386 (1.0%; 95% CI, 0.3 to 2.8%) Minor: 5/1092 (0.5%; 0.2 to 1.1%) Bowel injury: Diagnostic: 2/386 (0.5%; 0.03 to 2.0%) Minor: 4) Rate of conversion to laparotomy: NR 

Comme--Propoadnexa--No ma--PreproQuality Size of sample Numbe

Patient Applica

van Herendael, Beretta, Slangen, et al., 1995 #9830 

Geographical location: Antwerp, Belgium and Varese, Italy Dates: Jan 1989-Dec 1993 Size of population:121 Single center Two centers Morbidity definitions:

-Conversion -Anemia Length of followup after surgery:Median 20 months (range 1-60 months) 

Age:Mean: 36 Range: 18-63 Menopausal status (n [%]):NR Race/ethnicity (n [%]):NR Risk factors (n [%]):NR Loss to followup:

NR 

Symptomatic (n [%]):NR Detected by exam (n [%]):NR Detected by imaging (n [%]):NR Combination (n [%]):NR Additional data used for diagnosis:NR 

1) Mortality: 0/121 (95% CI, 0 to 4.5%) 2) Morbidity (total all complications): 2/121 (1.7%; 95% CI, 0.1 to 6.4%) 3) Specific complications: Anemia (no transfusion): 2/121 (1.7%; 95% CI, 0.1 to 6.4%) 4) Rate of conversion to laparotomy: 3/121 (2.5%; 95% CI, 0.6 to 7.5%) 

Comme--Preopdetail Quality Size of sample NumbePatient Applica
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Evidence Table 6 (continued) Study Study Design Patients Clinical Presentation Results CommYuen, Yu, Yip, et al., 1997 #6930 

Geographical location: Hong Kong Dates: Jul 1994-Sep 1995 Size of population:110 Single center Morbidity definitions:

-Complications -Cyst rupture rate Length of followup after surgery:8 weeks 

Age:Mean (SD): Laparotomy: 34.7 (8.8) Laparoscopy: 35.1 (10.3) Menopausal status (n [%]):Laparotomy Pre (< 45): 47 (94%) Post (> 55): 3 (6%) Laparoscopy Pre (< 45): 50 (96.2%) Post (> 55): 2 (3.8%) Race/ethnicity (n [%]):NR; presumably most Asian Risk factors (n [%]):NR Loss to followup:

4/110 (3.6%) 

Symptomatic (n [%]):Laparotomy: 32 (64%) Laparoscopy: 28 (54%) Detected by exam (n [%]):Asymptomatic: Laparotomy 18 (36%) Laparoscopy 24 (46.1%) Detected by imaging (n [%]):NR Combination (n [%]):NR Additional data used for diagnosis:Cystic masses with no irregular solid parts, thick septae, ascites; except dermoid 

1) Mortality: Laparotomy: 0/50 (95% CI, 0 to 10.6%) Laparoscopy: 0/52 (0 to 10.2%) 2) Morbidity (total all complications): Total: Laparotomy: 14/50 (28%; 95% CI, 18.5 to 43.1%) Laparoscopy: 4/52 (9.6%; 4.2 to 21.8%) Intraoperative Laparotomy: 1/50 (2.0%; 0 to 12.0%) Laparoscopy: 1/52 (1.9%; 0 to 11.6%) Postoperative: Laparotomy: 13/50 (26%; 16.8 to 41.0%) Laparoscopy 4/52 (7.8%; 2.9 to 19.3%) 

3) Specific complications: Laparotomy: Bladder injury: 1/50 Febrile morbidity: 10/50 UTI: 5/50 Urinary retention: 4/50 Wound infection: 1/50 Laparoscopy: Inf epigastric artery injury: 1/52 Febrile morbidity: 3/52 UTI: 2/52 4) Rate of conversion to laparotomy: 0/52 5) Cyst rupture rate Lapartomy: 9/30 (30%; 95% CI, 18.4 to 50.3%) Laparoscopy: 9/33 (27.3%; 16.5 to 46.4%) 

Comme-- Well-Quality Size of sample Numbesize caPatient Applica
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Evidence Table 7: Question 7: What are the estimated trade-offs resulting from various strategies for evaluation of the adnexal mas

Study Study Design Study Outcomes Sources for Model 

Probabilities 

Sources for Model Outcomes 

Results Co

Schapira, Matchar, and Young, 1993 #4870 

Type of model:Decision tree Population modeled (age, range):Cohort of healthy 40-year old women. Life expectancy based on average life expectancy in the US for a 40-year old woman. Strategies compared: No screening to screening using CA 125 and TVS in combination 

Life-expectancy No costs included 

No data used for transition probabilities. One time screen assumed. Used NCI data to determine prevalence of disease in 40 year old population. Adjusted for % that would present with symptoms. National Halothane study used for estimate of laparotomy mortality Simplifying assumptions: Assume that survival time for early disease detected by screening or clinical symptoms is equivalent Morbidity and mortality rates for diagnostic laparotomy are the same for pts with and without the disease No benefit from identifying benign disease One-time screen 

DEALE used to determine life expectancy. 1988 NCHS figures used to estimate average life expectancy. Note European citations 31 and 32 for life expectancy for those with early and late stage cancer. 

1) CA125+TVS – 40.192 years No Screen – 40.191 years 

2) No screening preferred if postoperative mortality rate > 7.32% or specificity of the test is 98.35% 3) Findings similar although LE gains not as great for women aged 65+. Specificity of test ≥ 99.25% in order for screening to be favored. 

Prasfas
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Evidence Table 7 (continued) Study Study Design Study Outcomes Sources for Model 

Probabilities 

Sources for Model Outcomes 

Results Co

Skates and Singer, 1991 #7000 

Type of model: Stochastic simulation model Population modeled: (age, range): Age 50 to 75 Strategies compared: CA-125 screening 

Years of life saved (undiscounted) 

Assumes o log-normal 

distribution for each stage 

o correlation 

between duration of adjacent stages is high, lower for stages far apart 

o coefficient of 

variation constant across all stages 

Estimates and ranges for duration of stage obtained from 2 gynecologic oncologists Stage I: 9 months Stage II: 4.5 months Stage III: 12 months Stage IV: 3 months Range corresponded to CV of approximately 50% Stage at clinical detection is independent of duration of disease; “major determinant of detection being the size and spread of the tumor and not it’s rate of growth” CA-125 produced from “tumor inception”Screen detected cases have identical survival within each 

Massachusetts General Hospital survival data for cancer Life tables for competing cause of death 

Based on “best” estimates of mean duration and variation of duration, 3.4 ± 1 year of life saved per case by annual screening; range of 1-5 years Overall increase in life expectancy (cases and noncases) not reported Results sensitive to assumptions about duration of early stage cancer, frequency of screening 

--Mpr(“athrint--Shisondisfroco--Adisdodis--Min re
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Evidence Table 7 (continued) Study Study Design Study Outcomes Sources for Model 

Probabilities 

Sources for Model Outcomes 

Results Co

stage as clinically detected cases Survival independent of age 

Tengs, Winer, Paddock, et al., 1998 #6010 

Type of model:Markov model Population modeled (age, range):30-year old woman testing for BRCA 1 and 2 Strategies compared: Testing for BRCA 1 and 2 with the following surgical options: Do nothing Mastectomy Mastectomy and oophorectomy Oophorectomy 

Life years saved quality adjusted life years saved No costs included 

Test accuracy provided by survey of companies marketing the tests SEER data for incidence – adjusted to account for the fact that data does not distinguish between those with genetic risk and those without. Literature used to estimate 92% risk reduction for breast cancer. Cancer experts for effectiveness of oophorectomy w/wout mastectomy Simplifying assumptions: “Operative mortality not included in the model as it would not have...an appreciable effect.” 

SEER data and literature (Rubin, NEJM, 1996) used for ovarian cancer 5 year survival NCHS for non-breast ovarian cancer survival Unclear where data for utilities came from 

1) Immediate mastectomy + oophorectomy offers greatest gains in survival when measured using LE Testing offers no benefit. 2) Optimal intervention depends on pre-test probability of carrying mutation. 3) When QALYs incorporated, depends on the test characteristics. If test is perfectly sens and spec then maximizes QALYs. If not perfectly sens 

and spec, then depends again on pretest probability of mutation. 

--OooBRdis--Nno
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Evidence Table 7 (continued) Study Study Design Study Outcomes Sources for Model 

Probabilities 

Sources for Model Outcomes 

Results Co

Urban, Drescher, Etzioni and Colby 1997 #6140 

Type of model: Stochastic simulation model Population modeled: (age, range): Age 50 to 80 Strategies compared: TVS and CA-125 

Years of life saved Age and stage based 

on SEER data Length of Stage 1 assumed to be independent of stage of disease at clinical diagnosis; Model assumes disease stages that correspond to FIGO staging with durations that are distributed log-normally with geometric means of 9, 4.5 12 and 3 months respectively, Stage 2 – 1⁄2 of Stage I; Stage 3, 1.333 times the length of Stage I; Stage 4, .333 times the length of Stage 1. Used data from Skates and Singer to model natural history 0.001 probability of death each time laparotomy is performed. 

Costs are based on a survey of labs, hospital clinics, and physician offices in Seattle, WA Note: used a 5% discount rate for the analysis 

Multimodal strategy using CA 125 with a threshold for positivity of either elevation above 35U/ml or doubling since the previous screen, followed by TVS only if CA 125 is positive was found to be efficient. (Cost/year of life saved is $64,000) Effectiveness and cost-effectiveness sensitive to assumptions about the behavior of early stage disease 

--Mprascliab
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Abbreviations used in the Evidence Tables 

2D Two-dimensional 

3D Three-dimensional 

AFP Alpha-fetoprotein 

AHRQ Agency for Healthcare Research and Quality 

AUC Area under the curve 

BME Bimanual examination 

BMI Body mass index 

CA-19-9 Cancer antigen 19-9 

CA-72-4 Cancer antigen 72-4 

CA-125 Cancer antigen 125 

CEA Carcinoembryonic antigen 

CI Confidence interval 

CPP Chronic pelvic pain 

CT Computed tomography 

F-FDG 18-Fluorodeoxyglucose 

FNA Fine needle aspiration 

FSH Follicle-stimulating hormone 

GI Gastrointestinal 

hCG Human chorionic gonadotropin 

ICD-9 International Classification of Diseases, Ninth Revision 

LDH Lactate dehydrogenase 

LMP Low malignant potential 

MRI Magnetic resonance imaging 

NIS Nationwide Inpatient Sample 

NA Not applicable 

NPV Negative predictive value 

NR Not reported 

OR Odds ratio 

PE Pelvic examination 

PET Positron emission tomography 

PI Pulsatility index 

PID Pelvic inflammatory disease 

PPS Papillary projection score 

PPV Positive predictive value 

PSV Peak systolic velocity 

RI Resistance index 

RMI Risk of Malignancy Index 

ROC Receiver operating characteristic 

SD Standard deviation 

Se Sensitivity 

SEM Standard error of the mean 

Sp Specificity 

TAG-72 Tumor-associated glycoprotein 72 

TAMXV Time-averaged maximum velocity 
D-338

TATI Tumor-associated trypsin inhibitor 

TVUS Transvaginal ultrasound 

US Ultrasound 

UTI Urinary tract infection 
D-339

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Appendix E: Peer Reviewers 

The Duke Evidence-based Practice Center is grateful to the following peer reviewers who 

read and commented on a draft version of this report: 

Susan M. Ascher, MD; Department of Radiology, Georgetown University Hospital; 

Washington, DC 

Andrew Berchuck, MD; Division of Gynecologic Oncology, Duke University Medical 

Center; Durham, NC 

Michael L. Berman; Division of Gynecologic Oncology, UCI Medical Center; Orange, CA 

Christie R. Eheman, MD; Centers for Disease Control and Prevention; Atlanta, GA 

Barbara Goff, MD; University of Washington School of Medicine; Seattle, WA 

Walter Kinney, MD; Department of Obstetrics and Gynecology, The Permanente Medical 

Group; Sacramento, CA 

Ann Kolker; Ovarian Cancer National Alliance; Washington, DC 

Herschel Lawson, MD; Center for Disease Control and Prevention; Atlanta, GA 

Saralyn Mark, MD; Department of Health and Human Services; Washington, DC 

Susan Meikle, MD, MSPH; Agency for Healthcare Research and Quality; Rockville, MD 

Valerie McGuire, PhD; Department of Health Research and Policy, Stanford University; 

Stanford, CA 

Edward E. Partridge, MD; Department of Obstetrics and Gynecology, University of 

Alabama; Birmingham, AL 

Mona Saraiya, MD, MPH; Centers for Disease Control and Prevention; Atlanta, GA 

George F. Sawaya, MD; Department of Obstetrics and Gynecology, UCSF; San Francisco, 

CA 

Howard T. Sharp, MD; University of Utah Hospitals and Clinics; Salt Lake City, UT 

Edward L. Trimble, MD, MPH; National Cancer Institute; Rockville, MD 

John R. van Nagell Jr., MD; Department of Obstetrics and Gynecology, University of 

Kentucky Medical Center; Lexington, Kentucky 
E-2

Nominations for peer reviewers were solicited from several sources, including the project’s 

technical expert panel and interested federal agencies. The list of nominees was vetted and 

approved by the Agency for Healthcare Research and Quality (AHRQ).