Comparative Analysis of Transperineal Versus Transrectal Approaches for MRI-Targeted Biopsy of the Prostate for the Detection and Characterization of Prostate Cancer
Phase: NA
Conditions: Prostate Cancer
Sponsor: NYU Langone Health

Version date: 10/05/2018 
1 of 19 
 
 
 
 
 
 
 
Comparative Analysis of Transperineal versus Transrectal 
Approaches for MRI-US Fusion-Targeted Biopsy of the Prostate 
for the Detection and Characterization of Prostate Cancer 
 
 
 
Division of Urologic Oncology 
NYU Langone Medical Center 
 
 
 
Principle Investigator: 
Samir S. Taneja, MD 
 
 
 
 
Sub-Investigators: 
 
 
 
 
Study staff:                                  
 
James Wysock, MD 
William Huang, MD 
Andrew Rosenkrantz, MD 
Marc Bjurlin, DO 
 
Richard Huang 
 
 
Protocol Number: 
s14-01550 
NCT Number: 
NCT03366792 
 
 
 
 
 
 
 
 
 
Version Date: 
10/05/2018  
Clinical Research 

Version date: 10/05/2018 
2 of 19 
 
 
Table of Contents 
 
          
  Page 
 
 
 
1. STUDY OVERVIEW ..............................................................................................................4 
 
2. OBJECTIVES  .........................................................................................................................4 
 
2.1   
Specific aims 
 
2.2  
Hypothesis 
 
3. BACKGROUND AND RATIONALE  ..................................................................................5 
3.1 
MRI  ..............................................................................................................................5 
 
4. STUDY DESIGN  .....................................................................................................................5 
4.1 
Study Participation ......................................................................................................7 
4.2 
Intervention ..................................................................................................................7 
4.3       End points  ....................................................................................................................8 
4.4 
Follow-up  ...................................................................................................................10 
4.5 
Statistics  .....................................................................................................................10 
 
5. DIAGNOSTIC AGENTS  .....................................................................................................11 
5.1 
Pre-enrollment procedures 
5.2 
Diagnostic intervention 
 
6. STUDY WORKFLOW  .........................................................................................................11 
 
 
6.1 
Recruitment 
 
6.2 
Timeline 
 
6.3 
Evaluation during and after intervention 
 
7. TOXICITIES/SIDE EFFECTS ............................................................................................13 
 
 
8.   DATA SAFETY MONITORING PLAN .............................................................................15 
  
9. CRITERIA FOR REMOVAL FROM STUDY...................................................................15 
 
10. INVESTIGATOR RESOURCES .........................................................................................15 
 
11. DATA MANAGEMENT ISSUES.........................................................................................16 
 
12. RESEARCH PARTICIPANT REGISTRATION AND RANDOMIZATION   ..............16 
 
13. REFERENCES .......................................................................................................................18 
 
 

Version date: 10/05/2018 
3 of 19 
 
 
1. SUMMARY OF TRIAL DESIGN 
 
This is a prospective, open-label, single-center trial to compare the efficacy of two 
different standard care approaches for MRI-ultrasound fusion-targeted prostate biopsy in 
men with high-suspicion lesions demonstrated on multi-parametric magnetic resonance 
imaging (mpMRI). 
 
Subjects are enrolled on the basis of elevated clinical suspicion for prostate cancer and 
area of high suspicion on mpMRI. Subject participation includes one standard care 
biopsy session during which both transperineal and transrectal biopsies will be obtained 
using ultrasound/MRI fusion guidance to sample suspicious lesions identified on MRI. A 
follow-up visit after one week will be in accordance with current post-biopsy 
management practices, and further clinical management will proceed as per standard of 
care following the biopsy results. 
 
 
 
The purpose of this study is to determine whether image-guided transperineal prostate 
biopsy can better characterize suspicious lesions in the prostate than transrectal biopsy. 
Accurate characterization of possible cancer foci is dependent on adequate targeting of 
suspicious lesions. Thus, the primary endpoint of the trial will be to determine the 
comparative efficacy of both approaches to accurately sample target lesions, which will 
be inferred from measuring the core-cancer length (CCL) in each positive core. Larger 
CCL when targeting the same lesion corresponds to better target sampling and will allow 
comparison of the relative ability of each biopsy approach to characterize lesions within 
the prostate.  
 
2.1  OBJECTIVES AND SCIENTIFIC AIMS    
 
Primary Objective:  
1. To assess the comparative efficacy of image-guided transperineal versus 
transrectal biopsy in characterizing prostate cancer. 
 
Secondary Objectives:  
1. To demonstrate the feasibility and investigate the cancer detection rate (CDR) 
of targeted transperineal biopsy, which has been shown to have a lower risk of 
infectious complications than transrectal prostate biopsy. 
 
Additional Observations: 
1. Occurrence of adverse events. 
2. Time spent in performing each biopsy technique. 
3. Correspondence of MRI suspicion score to presence of clinically significant 
cancer detected on biopsy 

Version date: 10/05/2018 
4 of 19 
 
 
 
2.2    HYPOTHESIS 
 
We will test the hypothesis that transperineal targeted biopsy will result in larger core-
cancer length than transrectal biopsy when targeted to the same cancerous lesion in the 
prostate.  
 
 
3. BACKGROUND and OVERVIEW OF THE STUDY 
 
3.1 Background and rationale 
 
Prostate cancer is the most common malignancy and the second most common cause of 
cancer death in men in the Western hemisphere.1 When suspicion for prostate cancer is 
sufficiently raised by a combination of increased prostate-specific antigen (PSA) level 
and abnormal digital rectal examination, definitive diagnosis is reliant on biopsy of the 
prostate gland. Today, expert recommendations from the American Urological 
Association (AUA) propose transrectal ultrasound (TRUS)-guided prostate biopsy 
involving 10-12 cores for diagnosis in men with adequate suspicion for prostate cancer.2  
This recommendation is based on optimizing the balance between adequate detection of 
clinically significant disease while minimizing detection of clinically insignificant 
disease, which has the potential to lead to overtreatment and increased morbidity.  
 
Transrectal access to the prostate is the most common approach for systematic biopsy. 
However, a concerning limitation of this approach is the rising rate of infectious 
complications, which is the leading cause of hospitalization after biopsy despite 
antimicrobial prophylaxis.3 Additionally, impeded access to the anterior and apical 
regions of the prostate from the rectum has lead to undersampling of this region and 
reported false-negative rates as high as 30%.4 Poor sampling of regions of the prostate 
which may harbor cancer foci leads to misdiagnosis or mischaracterization of disease. 
 
Transperineal biopsy of the prostate does not perforate the rectal wall, and thereby 
minimizes the risk of Gram-negative infection and rectal bleeding associated with 
transrectal biopsy. Because transperineal biopsy requires incision of the skin, the 
procedure presents a risk of infection and is often performed using local or regional 
anesthesia. Despite this, a 2012 meta-analysis concluded that transperineal biopsies do 
not have added risk of complications in comparison to transrectal biopsy, including 
infection.5 Additionally, a transperineal approach allows better access to the anterior 
region of the prostate. For patients with previously negative biopsies who still have an 
elevated risk of prostate cancer based on rising PSA, there is evidence to suggest that 
transperineal biopsies may be of clinical value in detecting previously undiagnosed 
disease.6 Improved sampling of cancer foci within the prostate can lead to more accurate 
characterization of disease, which ultimately serves as a major determinant in clinical 
decision-making. Finally, transperineal prostate biopsy follows the same physical 
approach as most modalities of focal therapy. Identification of cancers using this 
approach can thus optimize planning for focal therapy application in eligible patients. 

Version date: 10/05/2018 
5 of 19 
 
 
 
Recently, the emergence of targeted biopsy using multi-parametric magnetic resonance 
imaging (mpMRI) to identify foci of potentially malignant disease prior to biopsy has 
raised the potential for selective target sampling. By using a combination of MRI 
sequences to evaluate the prostate, including T2, diffusion weighted, and dynamic 
contrast-enhanced images, a 5-point Likert scale is used to grade lesions based on 
suspicion for prostate cancer. This technique has demonstrated superior diagnostic power 
for clinically significant prostate cancer, with sensitivity exceeding 80% for detecting 0.2 
cm3 of Gleason 4 + 3 or above and 0.5 cm3 of ≥ Gleason 3 + 4 in one study.7 As a result, 
transrectal biopsy using MRI-targeting has demonstrated improvement in selectively 
identifying clinically significant cancer and reduced overdetection of low-risk disease.8  
 
However, the current practice of transrectal needle placement still carries the same risks 
of undersampling of the anterior prostate and infection. Because a transperineal approach 
to the prostate allows improved sampling of the anterior region, it is reasonable to expect 
that an MRI-targeted biopsy using a transperineal approach may facilitate more accurate 
characterization of prostate cancer while also inherently limiting the risk of infection 
associated with transrectal biopsy.  
 
The purpose of this study is thus to examine whether a transperineal approach to prostate 
biopsy using MRI-targeting can provide improved characterization of prostate cancer 
compared to a transrectal approach. 
 
3.2   MRI-US Fusion Biopsy (Artemis) 
 
Computerized targeting of MP MRI lesions in our institution is routinely performed using 
Artemis™ software system.  The Artemis-Profuse software requires an initial transrectal 
ultrasound measurement of the prostate in order to obtain a 3D image of the prostate on 
ultrasound.  The computerized co-registration is then performed by software within the 
Artemis™ system and will fuse the MR imaging with real-time ultrasound imaging (this 
will require approximately 10 minutes).  Upon completion of co-registration, the 
Artemis™ system will be used to target suspicious lesions identified by MP MRI and 
these biopsies and locations will be mapped within the Artemis software.  A total of four 
computerized targeted biopsies per MP MRI lesion will be made using the Artemis™ 
system.  
 
4.  STUDY DESIGN 
 
Subjects are enrolled on the basis of elevated clinical suspicion for prostate cancer and 
identifiable area of suspicion on routine mpMRI. Subjects will initially be identified from 
the population of men undergoing outpatient management for suspected or known 
prostate cancer at NYU Smilow Prostate Cancer Center (SPCC) by members of the 
patient's treatment team or members of the investigational team. An investigator will 
screen the patients for eligibility in the study, and all information will be obtained either 
directly from the patient and/or their medical record. Initial screening will be based on 
suspicion for prostate cancer demonstrated by mpMRI of the prostate obtained as part of 

Version date: 10/05/2018 
6 of 19 
 
 
the standard of care at NYU SPCC. Screening will be followed by evaluation of 
exclusion criteria for enrollment into the study. 
Inclusion Criteria 
1. Men 40-85 years of age 
2. No contraindication to prostate biopsy (e.g. coagulopathy, medical condition 
prohibiting abstinence from anti-platelet or anticoagulation therapies, anatomical 
considerations) 
3. Area of suspicion or known cancer focus on previously obtained mpMRI of the 
prostate (at least one lesion with MRI suspicion score > 2/5) 
Exclusion Criteria 
1. Prior pelvic radiotherapy 
2. Evidence of urinary tract infection or significant urinary retention 
3. Prostate instrumentation (e.g. prostate biopsy, transurethral prostate procedure) 
within 2 months prior to mpMRI 
4. No evidence of suspicious lesions on mpMRI 
5. Irreversible coagulopathy 
6. Contraindication to sedation 
 
 
4.1  Study participation 
Subject participation includes one standard care biopsy session during which both 
transperineal and transrectal biopsies will be obtained using ultrasound/MRI fusion 
guidance to sample suspicious lesions identified on MRI. Two biopsy cores per lesion 
with MRI suspicion score > 2/5 will be obtained using each approach per standard 
practice. A follow-up visit after one week will be in accordance with current post-biopsy 
management practices, and further clinical management will proceed as per standard of 
care following the biopsy results. 
 
Before enrollment, patients will undergo routine 3 Tesla mpMRI with T2 3D, DCE and 
DWI imaging following the NYULMC standard prostate imaging protocol.  Each study 
will require approximately 45 minutes to acquire imaging.  Prospective candidates for the 
study will undergo this imaging prior to enrollment into the study and biopsy. The results 
of the mpMRI will be provided according to the standardized NYULMC template.  
Lesions identified on mpMRI with high suspicion score (3, 4 or 5 out of 5) will be 
considered for targeting on biopsy.  Men without evidence of lesion on mpMRI or with 
low suspicion lesions are not eligible for the study.  
  
Study participants will then undergo standard of care pre-biopsy procedure including 
initiation of peri-procedure antibiotics and pre-procedure Fleets enema.  Biopsy will be 
performed in the Smilow Prostate Cancer Center.  All biopsies will be performed using 
general anesthesia per standard of care protocol.  Biopsies will then be performed 
according to the standard procedure detailed below.   
 

Version date: 10/05/2018 
7 of 19 
 
 
4.2  Intervention 
 
Computerized targeting of mpMRI lesions will be performed using Artemis™ software 
system per standard practice.  This software requires an initial transrectal ultrasound 
measurement of the prostate in order to obtain a 3D image of the prostate on ultrasound.  
The computerized co-registration will then be performed by software within the 
Artemis™ system and will fuse the MR imaging with real-time ultrasound imaging (this 
will require approximately 10 minutes).  Upon completion of co-registration, the 
Artemis™ system will be used to target suspicious lesions identified by mpMRI and 
these biopsies and locations will be mapped within the Artemis software.  A total of two 
computerized targeted biopsies per mpMRI lesion will be made using the Artemis™ 
system using each biopsy approach.  A maximum of three mpMRI lesions will be 
targeted.  The operator of the Artemis™ system biopsies will not be blinded to the 
mpMRI results.  After completion of the targeted transrectal prostate biopsy, the patient 
will be repositioned to lithotomy position to expose the perineum. The physician will 
replace the transrectal ultrasound probe and obtain biopsies through transperineal needle 
placement into the same targets planned on the Artemis fusion software. Biopsy 
specimens will be collected in labeled jars for transport to the pathology lab in 
accordance with biopsies that are already performed as part of a patient’s regular 
treatment at NYU Smilow Cancer Center. No additional cores will be collected for this 
study than what is normally taken for a standard of care whole biopsy (non-targeted and 
targeted biopsy).   The targeted biopsies will require between 5-10 minutes of time per 
approach to acquire.  After pathology analysis, leftover tissue remaining after analysis 
will be not be kept for further research analysis and will not be discarded.  All biopsies 
will be archived as required by law.  
 
This is an outpatient procedure.  Patents will undergo a voiding trial prior to discharge.  If 
they fail same day voiding trial, a Foley catheter will be placed with a second trial 
performed approximately one week after treatment per standard care.   
 
The targeted biopsies will require 4 cores per lesion for each patient.  A maximum of 
three mpMRI lesions will be allowed to be targeted.  It is very rare (<5% of positive 
mpMRI) for there to be more than three lesions identified on mpMRI.  The 4 cores taken 
per targeted lesion is the current standard at the Smilow Prostate Cancer Center.  
Typically, a biopsy will be done through one approach (transrectal or transperineal).  For 
the purposes of this study, both approaches will be used per targeted lesion.  However, 
only two cores will be taken for each approach which will not result in any extra cores 
taken for research purposes.  As both approaches are considered routine, performance of 
both approaches during a biopsy sitting should not result in an increased likelihood of 
comorbidity and will not extend a subject’s time under anesthesia by any significance. 
 
Risks of performing the two targeted biopsy approaches in one setting are the same risks 
inherent to traditional systematic standard care prostate biopsy, including bleeding, 
infection, urinary retention, and voiding dysfunction. 
 
4.3  Endpoints 
 

Version date: 10/05/2018 
8 of 19 
 
 
i. 
Predictor variables:  
a. Biopsy approach  
i. Variable type: Dichotomous (categorical) 
ii. Potential outcomes: Transperineal vs Transrectal 
b. Location of target lesion within the prostate is a prominent consideration for 
targeting accuracy, as lesions in the anterior prostate are known to be difficult 
to access using a posterior approach (transrectal biopsy). 
i. Variable type: Categorical 
ii. Potential outcomes: (Left vs right) + (Anterior vs posterior) + (apex vs 
midgland vs base) 
 
ii. 
Outcome variables:  
a. Length of core-cancer involvement - A larger amount of cancer within each 
core as a result of improved lesion targeting provides better disease 
characterization. Data regarding core cancer length measurements in 
transperineal targeted biopsy is limited. Previous studies have shown median 
CCL in MRI-targeted transperineal biopsy to be 2mm (range 1-5mm).11 
However, MRI-guided biopsies were performed under cognitive US-MRI 
fusion and thus did not benefit from automated image coregistration, which 
was shown to significantly increase mean CCL.12   To our knowledge there is 
no precedent for estimation of CCL in targeted transperineal biopsies using 
automated US/MRI fusion. 
i. Variable type: Continuous 
ii. Scale: millimeters 
iii. Validity: Greater tumor length per core provides better diagnostic 
information and has been shown to correlate with Gleason score and 
pathologic stage at radical prostatectomy.9 
iv. Source: Histological analysis (pathologist's report) 
 
b. Number of cancers detected using each approach- The relative cancer 
detection rates (CDRs) between approaches correlate to the sensitivity of 
detecting cancer in high risk foci, and should be directly compared between 
the two modalities as a marker of targeting accuracy.  
i. Variable type: Continuous 
ii. Potential outcomes: 0-100% 
iii. Validity: Since each lesion serves as its own control, a higher 
percentage of cancer-positive results using a given approach directly 
corresponds to accuracy of targeting using that technique 
iv. Source: Histological analysis (pathologist's report) 
 
c. Concordance of Gleason score between biopsy and prostatectomy- This 
measurement correlates to the accuracy of the biopsy technique compared to 
pathological analysis of the excised prostate gland (gold standard) and is the 
ultimate metric for characterization of disease. However, this is likely to 
include only a small number of study subjects and therefore may not 
demonstrate a definitive difference between the two techniques.  
i. Variable type: Categorical 

Version date: 10/05/2018 
9 of 19 
 
 
ii. Potential outcomes: True concordance, upstage at final pathology, 
downstage at final pathology 
iii. Source: Histological analysis (pathologist's report) 
 
4.4  Follow-up 
 
The first clinical follow-up visit will be scheduled 1 week after biopsy.  At that time the 
patient’s clinical condition will be assessed according to standard of care post-biopsy 
evaluation.  All study participants will be evaluated for additional complications to 
ensure that the targeted biopsies do not confer additional risk for complications.  
However, given that the maximum number of biopsies will be within the standard of care 
range, we do not anticipate an increase in complication rates.  Biopsy results will be 
revealed to the patient at that time.  
 
The primary endpoint of the trial will be assessed upon accrual and biopsy of the planned 
number of study participants.  The primary objective will be assessed by quantifying the 
core cancer lengths of positive biopsy results (diagnosis of CaP, Gleason 3 or higher, in 
any given core) for each technique of targeted biopsy.  Secondary endpoints will be 
evaluated via rate of positive biopsy using transperineal versus transrectal targeted 
techniques for prostate sampling.  Furthermore, cancer characteristics including Gleason 
score and disease volume will be evaluated across techniques.  All adverse event data 
will also be recorded.  
 
Patients diagnosed with CaP will be offered standard of care treatment options as based 
upon the stage and grade characteristics of the identified disease.  Targeted biopsy results 
that reveal CaP will be considered in the same fashion as CaP diagnosed with standard of 
care biopsy.  All recommendations regarding the appropriate management of any CaP 
diagnosed will then be based upon biopsy features and patient decision. 
 
  4.5 
Biostatistics     
 
Sample size justification  
Evaluation of cancer-core length will be the primary endpoint, as reported above. The 
necessary sample size will be powered to observe a significant difference in CCL 
between techniques. The limited available data regarding CCL obtained from 
transperineal targeted biopsy may not serve as an accurate estimate within our population 
due to potential differences in targeting techniques as well as patient demographics and 
selection criteria for biopsy. 
 
Our data from a recent study of patients receiving both targeted and systematic transrectal 
biopsies demonstrated that the mean CCL per positive core per patient is 4.7 ± 3.3mm in 
MRI-targeted transrectal biopsies compared to 2.8 ± 2.4mm in systematic biopsies.12 The 
mean difference of 1.9mm was significant (p = 0.03) in a cohort of 67 biopsy-naive men 
out of 125 recruited at our institution over 9 months, and likely reflected improved 
sampling of cancer foci. Similarly, retrospective analysis of 601 MRI-targeted transrectal 
biopsies at our institution demonstrates that the mean difference between the largest CCL 

Version date: 10/05/2018 
10 of 19 
 
 
and second largest CCL found on targeted biopsy of the same lesion is 2.1 ± 2.4mm. This 
difference in CCL may also be considered as reflective of a discrepancy in lesion 
targeting accuracy between two cores. The average of these two estimates of difference in 
CCL (1.9mm and 2.1mm) is 2.0mm.  
 
For the present study, a conservative estimate of the mean difference in CCL obtained by 
transperineal vs transrectal targeted biopsy is 1.0mm, or half of the aforementioned 
difference of 2.0mm. Assuming a tolerance for α error of 5%, 80% power, and a mean 
difference of 1.0 ± 2.4mm, a sample size of 46 cancer-positive lesions would be needed 
to demonstrate a difference in targeting ability between the two biopsy techniques.  
 
Positive results will be compared on a per-lesion basis, where the largest CCL of the two 
cores taken from each approach will be compared. Preliminary data from MRI-targeted 
biopsy since 2012 at the NYU SPCC has demonstrated approximately 55% and 95% 
cancer detection rate among patients with MRI suspicion scores of 4 and 5, respectively. 
Additionally, the average number of cancer-positive lesions among men with prostate 
cancer detected on targeted biopsy is 1.2. Given the approximate time-course for the 
study, accrual rate,cancer detection rate in our previous trial, and potential screen failures, 
we anticipate that recruitment of 80 patients will be feasible and provide sufficient power 
to demonstrate a difference of 1.0 mm in cancer-core length between the two 
techniques.This sample size also accounts for potential screen failure for patients 
consented who have not yet had their standard of care MRI of the prostate.  
 
Statistical analysis for primary objective 
 
Measurements of cancer-core length from transrectal and transperineal biopsies may be 
compared using a two-tailed, paired samples T test or Wilcoxon Signed Rank Test in 
order to accept or reject the hypothesis that transperineal biopsy provides higher CCL per 
positive core than transrectal biopsy.  
 
Statistical analysis for secondary objectives 
 
Cancer detection rate (CDR) and concordance may also be compared between techniques 
using McNemar's test. Multivariate analysis to determine predictors of improved 
diagnosis with either technique will be performed using binomial logistic regression. 
 
 
5. DIAGNOSTIC AGENTS 
 
5.1    Pre-Enrollment Procedures 
 
A. MRI:  Multi-parametric MRI of the Prostate 
Eligible candidates for this study will have undergone a pre-biopsy mpMRI of the 
prostate as part of their standard care.  Men identified as having highly suspicious 
regions on this MRI will be offered enrollment into the study to target these areas.  
All mpMRI procedures will have been performed according to standard of care for 

Version date: 10/05/2018 
11 of 19 
 
 
this radiology procedure.  All mpMRI of the prostate will be performed using a 3 
Tesla magnet following the NYULMC standard prostate imaging protocol.  Imaging 
will be conducted by pelvic phased array coils.  No endorectal coil will be utilized.  
Suspicion of cancer will be graded according to the standard NYULMC Department 
of Radiology scale.  
 
5.2    Diagnostic Intervention 
 
B. Artemis Biopsy:  Artemis, Eigen’s 3-D prostate imaging device, is a FDA approved 
Class II medical device for planning and guiding a transrectal prostate biopsy. 
 
In MRI/TRUS fusion planning, the previously available imaging study (MRI) is used 
by a trained radiologist to mark out regions of interest for targeting. This information 
is transferred to Artemis when a fusion plan is initiated. The MRI image and the 3D 
TRUS image are co-registered, and regions of interest marked on the MRI are 
mapped on to the 3D TRUS image. The urologist then plans biopsy targets in these 
regions of interest that are overlaid on the 3D TRUS image.  
 
After planning, traditional needle guidance to the planned location as per normal 
biopsy technique is performed. At all times, the physician uses the live ultrasound 
image and Artemis guidance to biopsy tissue from the planned location. Transrectal 
Artemis biopsy is not investigational. This is currently the standard of care biopsy in 
our practice at NYU.  It is FDA approved for this application, has several publications 
regarding technique from many institutions, and NYU urologic oncologists have 
performed roughly 1200 such biopsies at NYU since 2009, as part of our standard 
clinical protocol. 
 
A new attachment will be added to the Artemis device to facilitate transperineal 
targeted biopsy. Transperineal biopsy itself is not investigational. This is a well-
described biopsy technique that is used often in contemporary clinical practice, 
frequently to improve sampling when patients have a history of negative transrectal 
biopsies. The attachment to the Artemis device does have 510K regulatory clearance 
and we do not anticipate additional risks to standard of care transperineal biopsy. 
 
After obtaining 2 cores of the suspicious lesion via transrectal Artemis biopsy, the 
patient is repositioned to allow for transperineal needle access. The Artemis fusion 
system allows for visualization of the previously accessed target and 2 additional 
cores are obtained via transperineal placement of the biopsy needle. For sequential 
patients, we will switch the order (transperineal before transrectal) for every other 
patient in order to mitigate any bias from starting with the same approach for each 
case. 
 
6... STUDY WORK FLOW 
 
6.1 Recruitment 

Version date: 10/05/2018 
12 of 19 
 
 
Subjects will initially be identified from the population of men undergoing outpatient 
management for suspected or known prostate cancer at NYU Smilow Prostate Cancer 
Center.  Potential participants will be those under the care of the investigators. A member 
of the research teamwill screen the patients for eligibility for the study through chart 
review, and all information will be obtained either directly from the patient and/or their 
medical record. Screening criteria include PSA history, digital rectal exam, and mpMRI 
to determine initial eligibility, which will be followed by evaluation of exclusion criteria 
for enrollment into the study. Any information collected for this study in a patient who is 
determined to be ineligible will be destroyed.  
 
A member of the research team will inform patients of their eligibility for the trial and 
potential risks and benefits. Decision as to whether or not to take part in this study is 
completely voluntary and formal consent will be obtained prior to pre-treatment 
evaluation.  
 
6.2 Study Timeline  
 
i. 
Visit 1 (week 0) 
a. Baseline visit to determine patient eligibility based on careful review of 
patient medical history and risk for prostate cancer. If available, patient 
mpMRI will be reviewed as well. This visit will occur as part of their 
standard clinical care with the investigator for suspected or known prostate 
cancer.  The research team will review the consent form with the potential 
subject and answer all questions.  Once eligibility is confirmed and the 
patient agrees to participate in the study, informed consent is signed, and 
the patient will be scheduled for prostate biopsy at their next visit (2-4 
weeks). 
b. If no mpMRI is available, the patient will be scheduled for this imaging 
study as per our institution's standard of care before finally determining 
eligibility.  This will be done regardless of participation in the study. 
ii. 
Visit 2 (week 2-4) 
a. Approximately 2-4 weeks after the initial visit, each subject will return for 
prostate biopsy. All biopsies will be done in one operative session and will 
be performed as outpatient procedures. 
iii. 
Visit 3 (week 4-5) 
a. All study participants will have a follow up visit approximately one week 
following biopsy for clinical evaluation of recovery from biopsy and to 
review biopsy results.  At this point, all patients will be managed 
according to standard of care based upon biopsy results. 
 
 
6.3  Evaluation During and After Intervention 
 
Subjects will be monitored by a qualified anesthesiologist during and after the procedure. 
Following the biopsy, patients will be relocated to the recovery bay adjacent to the 
procedure room for observation. All patients will be evaluated clinically one week after 

Version date: 10/05/2018 
13 of 19 
 
 
biopsy to assess for biopsy complications including risk of infection, persistent hematuria 
or rectal bleeding.  Any identified complications will be recorded and treated according 
to severity.   
 
7.  TOXICITY / SIDE EFFECTS (Adverse Event Reporting) 
 
7.0  Definitions: 
 
7.0.1   Adverse Event:  Any unfavorable and unintended sign, symptom or 
disease temporally associated with the use of a medical treatment, regardless of 
whether it is related to the medical treatment. 
7.0.2  A serious adverse event (SAE) is defined as any adverse event that results 
in death, a life-threatening experience, inpatient hospitalization, prolongation of 
existing hospitalization, persistent disability, or congenital anomaly or birth 
defect.   
7.0.3 Study therapy is the required treatment or procedure defined on the 
protocol. 
7.0.4  Non-protocol therapy is defined as any treatment or procedure not 
described in the protocol 
 
7.1 Adverse event assessment: 
7.11 
The type of event using NCI Common Toxicity Criteria for Adverse 
Events (CTCAE) version 3.0 will be identified and graded for severity. 
7.12  
The relationship of the adverse event to the therapy or procedure will be 
determined as follows:  Unrelated; Unlikely; Possible; Probable;  Definite   
7.13  
For reporting purposes, an adverse event is considered unexpected when 
either the type of event or severity of the event is not listed in the study consent 
 
7.2  Serious Adverse Events (SAEs): 
7.11.A   All study-related, unexpected Grade 3 or 4 SAEs will be immediately 
reported to the IRB.  These toxicities will be reviewed by the principal 
investigator and appropriate measures taken in terms of delaying, modifying or 
stopping therapy. 
7.11.B The descriptions and grading scales found in the revised NCI Common 
Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized 
for adverse event reporting (http://ctep.cancer.gov/reporting/ctc.html).  
7.11.C  SAEs must be followed until resolution or deemed irreversible.   
 
7.2  Routine reporting: 
 
7.21.A Institutional Review Board rules. 
A reportable events log will kept over the course of the study for all adverse events as 
well as all protocol deviations and exceptions.  This log will be submitted to the IRB 
for review during each annual continuation submission. 
7.3 Potential Adverse Events 

Version date: 10/05/2018 
14 of 19 
 
 
This is a minimal risk study where loss of confidentiality is a potential risk.  The PI will 
adhere to a data monitoring plan to ensure there is no breach in confidentiality.   
 
-There is also risk associated with prostate biopsy (transrectal or transperineal).  This 
includes bleeding, infection, urinary retention, and erectile dysfunction.  Because it is not 
standard to have both approaches done in one sitting for a biopsy, the PI will also monitor 
the study for an unexpected increase in risk for these potential adverse events.       
 
 
7.5 Potential Benefits of Study 
• This study provides an additional opportunity to sample areas of suspicion for 
prostate cancer, and may help better characterize disease to provide more 
information to guide subjects’ treatment. It is hoped the knowledge gained will be 
of benefit to others in the future 
7.6  Informed Consent Process   
Study subjects will meet with a member of the research team, who will obtain informed 
consent in person by paper, during an office visit. The consent form will be signed and 
dated by the participant.  In the event the participant is illiterate, an impartial witness will 
also sign and date the consent form to indicate that the consent form was presented orally 
to the participant.  The member of the research team obtaining consent will also sign and 
date the form.  Afterwards, a copy of the consent form will be provided to the participant 
for their personal records. A log will be kept documenting informed consent and each 
participant will be added to the log after signing the consent form.  The original signed 
consent form will be added to the participant’s study file. 
7.7  Privacy and Confidentiality 
 
Study/subject documents will be de-identified and labeled according to trial entry 
number. Only the PIs and Study coordinator will have access to this data. Data will be 
kept in a secure, password-protected database kept on the PI’s computer in the Urology 
office. No identifying information will be kept in this database. 
 
 
7.9 Cost/Reimbursement 
Eigen (Grass Valley, CA) will provide the transperineal biopsy attachment to our 
institution. Participants will be receiving medical care as a part of this research study, 
which is done as a part of regular care. The patients or the insurance company will be 
charged or held responsible for the costs of that care. Subjects will not receive 
compensation for participating in this study. 
 
 
 

Version date: 10/05/2018 
15 of 19 
 
 
8.  DATA SAFETY MONITORING PLAN 
-Dr. Samir Taneja will be responsible for overseeing the data safety monitoring plan 
-All consent forms, once signed, will be coded numerically.  Each consented patient will 
have that matching number assigned to him as the source of identification for 
participants.  This information will be kept in a limited database with identifiers such as 
name and medical record and will be used to identify subjects in a separate informational 
database containing no identifiers and only information relevant for analysis to the study. 
Each database will be kept on separate computers and can only be accessed by the PI and 
Study Coordinator.  They will be kept in a secure password protected folder on the NYU 
network for server redundancy as implemented by NYU Medical Center to ensure data 
protection. Signed consent forms along with the participant’s study file will be locked 
away in a secure room that can accessed only by the Study Coordinator. 
 
-An initial review of adverse events from the prostate biopsy will be done after 5 patients 
have undergone prostate biopsy (transrectal and transperineal).  If after initial review, the 
risks associated through performing both approaches in one sitting are minimal as 
expected, review for adverse events will be done quarterly.  Any serious adverse events 
will be reported to the IRB within 48 hours.   
 
-Dr. Samir Taneja will ensure adherence to the data safety plan and confidentiality 
through observation and making quarterly checks.  Any serious breaches in 
confidentiality will be reported to the IRB within 48 hours.  
 
-There are no formal stopping rules for the study.  A summary report will be submitted to 
the IRB during each annual continuation detailing any adverse event associated with 
prostate biopsy as well as any failures to adhere to the study design and data monitoring 
plan.   
 
9.  CRITERIA FOR REMOVAL FROM STUDY   
The patient may withdraw consent for the study at any time.  
If at any time the patient is found to be ineligible for the protocol as designated in the 
section on Criteria for Patient/Subject Eligibility (i.e., a change in diagnosis), the patient 
will be removed from the study. 
10.  INVESTIGATOR RESOURCES 
10.1 Qualifications 
Dr. Samir Taneja is the Principal Investigator of the Study.  He is the Director of the 
Division of Urologic Oncology in the Department of Urology at the NYU Langone 

Version date: 10/05/2018 
16 of 19 
 
 
Medical Center.  He is also the Program Leader of the Genitourinary Oncology Program 
of the NYU Cancer Institute.   
 
Sub-Investigators of this study will be Drs. James Wysock, William Huang, and Marc 
Bjurlin. 
Dr. James Wysock is an Assistant Professor in the Department of Urology at NYU 
Langone Medical Center.   
Dr. William Huang is a Associate Professor in the Department of Urology.  He is also 
Co-Director of the Robotics Program as well as Chief of Urology Service at Tisch 
Hospital. 
Dr. Marc Bjurlin is a Clinical Assistant Professor in the Department of Urology. 
All Investigators will be performing all procedures, including biopsies, on participants 
currently under their respective care. 
Dr. Andrew Rosenkrantz is an Assistant Professor from the NYU Department of 
Radiology.   His responsibilities will include performing and interpreting the imaging 
portions of the trial. 
Richard Huang will be responsible for data entry and management and is familiar with 
IRB regulations and HIPAA compliance.   
10.2 Use of NYU Facilities 
Several NYU facilities will be used for this trial.  The Smilow Prostate Cancer Center is a 
treatment facility which contains an OR, RR and will also be used for patient follow-up 
visitations.  NYU Pathology lab will be used for histologic examination.  Radiology 
testing will be done at an FPO here at NYU and laboratory studies will also be done at 
the NYU lab.   
 
10.3 Conflict of Interest 
There are no potential conflicts of interest for this trial. 
11.0 DATA MANAGEMENT ISSUES  
A Research Study Assistant (RSA) will be assigned to the study. The responsibilities of 
the RSA include project compliance, data collection, abstraction and entry, data 
reporting, regulatory monitoring, problem resolution and prioritization, and coordinate 
the activities of the protocol study team. 
The data collected for this study will be entered into a secure database. Source 
documentation will be available to support the computerized patient record. 

Version date: 10/05/2018 
17 of 19 
 
 
12.0 RESEARCH PARTICIPANT REGISTRATION AND RANDOMIZATION  
12.1    Quality Assurance  
Weekly registration reports will be generated to monitor patient accruals and 
completeness of registration data. Routine data quality reports will be generated to assess 
missing data and inconsistencies.   Accrual rates and extent and accuracy of evaluations 
and follow-up will be monitored periodically throughout the study period and potential 
problems will be brought to the attention of the study team for discussion action. 
Random-sample data quality and protocol compliance audits will be conducted by the 
study team, at a minimum of two times per year, more frequently if indicated. 
Records to be Kept 
12.2  Investigator Study Files: The Principal Investigator is responsible for 
maintaining study files for a period of 2 years after the investigation is discontinued.  
The following documents should be kept in the study files: 
12.2.1    Curricula vitae of all sub investigators and the current Human Subjects 
Protection certifications 
12.2.2  The original protocol and all amendments 
12.2.3   Final IRB approval, annual renewals and all IRB correspondence 
12.2.4   Blank Case Report Forms 
12.2.5  Copy of all IRB approved Informed Consent forms with applicable version  
 
date 
12.2.6  Copy of all patients’ signed informed consent forms 
12.2.7  The final completed case report forms for all patients is the  
             responsibility of the investigator.  They will be available for review by the  
 
             investigator of the trial, health care personnel involved in this study, the IRB,  
 
 
DHHS, and the FDA.  

Version date: 10/05/2018 
18 of 19 
 
 
13.0       REFERENCES  
1.  
Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA. Cancer J. Clin. 
2014;64:9-29. doi:10.3322/caac.21208. 
2.  
Taneja SS, Bjurlin MA, Carter HB, et al. AUA/Optimal Techniques of Prostate 
Biopsy and Specimen Handling. In: AUA White Paper.; 2013. 
3.  
Loeb S, Vellekoop A, Ahmed HU, et al. Systematic review of complications of 
prostate biopsy. Eur. Urol. 2013;64:876-892. doi:10.1016/j.eururo.2013.05.049. 
4.  
Levine MA, Ittman M, Melamed J, Lepor H. Two consecutive sets of transrectal 
ultrasound guided sextant biopsies of the prostate for the detection of prostate 
cancer. J. Urol. 1998;159:471-476. doi:10.1016/S0022-5347(01)63951-X. 
5.  
Shen P-F, Zhu Y-C, Wei W-R, et al. The results of transperineal versus transrectal 
prostate biopsy: a systematic review and meta-analysis. Asian J. Androl. 
2012;14(2):310-5. doi:10.1038/aja.2011.130. 
6.  
Emiliozzi P, Corsetti A, Tassi B, Federico G, Martini M, Pansadoro V. Best 
approach for prostate cancer detection: A prospective study on transperineal versus 
transrectal six-core prostate biopsy. Urology 2003;61:961-966. 
doi:10.1016/S0090-4295(02)02551-7. 
7.  
Villers A, Puech P, Mouton D, Leroy X, Ballereau C, Lemaitre L. Dynamic 
Contrast Enhanced, Pelvic Phased Array Magnetic Resonance Imaging of 
Localized Prostate Cancer for Predicting Tumor Volume: Correlation With 
Radical Prostatectomy Findings. J. Urol. 2006;176:2432-2437. 
doi:10.1016/j.juro.2006.08.007. 
8.  
Bjurlin M a, Taneja SS. Standards for prostate biopsy. Curr. Opin. Urol. 
2014;24:155-61. doi:10.1097/MOU.0000000000000031. 
9.  
Chiang IN, Chang SJ, Pu YS, Huang KH, Yu HJ, Huang CY. Major complications 
and associated risk factors of transrectal ultrasound guided prostate needle biopsy: 
A retrospective study of 1875 cases in Taiwan. J. Formos. Med. Assoc. 
2007;106:929-934. doi:10.1016/S0929-6646(08)60063-7. 
10.  
Berger AP, Gozzi C, Steiner H, et al. Complication rate of transrectal ultrasound 
guided prostate biopsy: a comparison among 3 protocols with 6, 10 and 15 cores. 
J. Urol. 2004;171:1478-1480; discussion 1480-1481. 
doi:10.1097/01.ju.0000151626.18422.65. 
11.  
Kasivisvanathan V, Dufour R, Moore CM, et al. Transperineal magnetic resonance 
image targeted prostate biopsy versus transperineal template prostate biopsy in the 

Version date: 10/05/2018 
19 of 19 
 
 
detection of clinically significant prostate cancer. J. Urol. 2013;189(3):860-6. 
doi:10.1016/j.juro.2012.10.009. 
12.  
Wysock JS, Rosenkrantz AB, Huang WC, et al. A Prospective, Blinded 
Comparison of Magnetic Resonance (MR) Imaging-Ultrasound Fusion and Visual 
Estimation in the Performance of MR-targeted Prostate Biopsy: The PROFUS 
Trial. Eur. Urol. 2013;66(2):343-351. doi:10.1016/j.eururo.2013.10.048.