Clinical trial NCT00003645
Conditions: Prostate Cancer
Keywords: stage I prostate cancer stage II prostate cancer
Sponsor: M.D. Anderson Cancer Center
Start date: 1999-06-14; Completion date: 2017-03-20
Enrollment: 64 participants; Allocation: RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
RATIONALE: Testosterone can stimulate the growth of prostate cancer cells. Hormone therapy using leuprolide and flutamide may fight prostate cancer by reducing the production of testosterone. It is not yet known whether receiving leuprolide and flutamide is more effective than receiving no further therapy.

PURPOSE: Randomized phase III trial to determine the effectiveness of hormone therapy in treating patients who have stage I or stage II prostate cancer that is at high risk of recurrence and who have already undergone surgery.

Detailed description:
OBJECTIVES:

* Determine the effect of one year of adjuvant hormonal ablation on disease-free survival at 5 years in node-negative radical prostatectomy patients at high risk for progression.
* Determine the effect of this treatment on the incidence of androgen independent prostate cancer and on disease specific and overall survival.
* Determine the impact of one year of total androgen ablation on quality of life and serum testosterone levels.
* Assess differences in quality of life between wives of patients in the androgen ablation condition compared to wives of patients in the control condition.
* Obtain blood samples from patients at high risk for failure post-prostatectomy to evaluate serum markers of prognosis.

OUTLINE: This is a randomized study. Patients are randomized to one of two treatment arms.

* Arm I: Patients receive leuprolide intramuscularly once every 3 months and oral flutamide three times daily for 1 year.
* Arm II: Patients receive no initial treatment. Quality of life is assessed every 6 months for 5 years. Quality of life of wives/partners of patients is assessed every 6 months for two years.

Patients are followed every 3 months for 1 year and then every 6 months for 4 years.

PROJECTED ACCRUAL: A total of 496 patients (248 per treatment arm) will be accrued for this study within 3.5 years.

Arms: arm 1: Arm I: Patients receive leuprolide intramuscularly once every 3 months and oral flutamide three times daily for 1 year. arm 2: Arm II: Patients receive no initial treatment.
Interventions: intervention 1: Flutamide intervention 2: Leuprolide Acetate
Intervention descriptions: intervention 1: 10.8 mg intramuscularly once every 3 months for 12 months intervention 2: 50 mg tablet orally daily for 12 months

Protocol documents:
Prot_SAP_000.pdf: 
Protocol ID97-077 
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1.0  
Objectives 
 
 
a. To determine if one year of adjuvant hormonal ablation in node negative radical 
prostatectomy patients at high risk for progression will result in an improvement 
in disease-free survival at five years.  
b. To determine the impact of one year of total androgen ablation on quality of life.  
c. To assess differences in quality of life between wives/partners of patients in the 
androgen ablation condition compared to wives/partners of patients in the control 
condition. 
d. To obtain blood samples and tissue blocks from tumor and normal prostate from 
patients at high risk for post prostatectomy to evaluate markers of prognosis. 
  
2.0   Background 
 
Radical prostatectomy has become the treatment of choice for many patients with 
organ confined prostate cancer (AJCC T1-T2) who have at least a ten year life 
expectancy. Data from surgical series suggest that 10-15 year overall survivorship 
of 88-64% (respectively) can be achieved with disease-free survivorship ranging 
from 72-62% in patients with negative lymph nodes (1-3). Serum prostate specific 
antigen (PSA) testing has redefined the threshold for surgical cure of prostate 
cancer. Since PSA is produced exclusively by prostate tissue (benign and 
malignant) surgical removal of the gland should result in an undetectable value. 
Failure of the serum PSA to become undetectable post radical prostatectomy or a 
subsequent rise from a prior undetectable value is now considered to represent 
treatment failure (4). PSA recurrence (biochemical failure) has been shown to 
invariably antedate clinically recognized disease by several months, or even years 
depending on site of relapse and the biological aggressiveness of the disease. 
Thus, serum PSA represents the earliest known marker for disease recurrence and 
heralds clinical relapse (4, 5). 
 
Overall, freedom from any relapse (PSA or clinical) in patients treated with 
radical prostatectomy ranges from 61-87% and 41-71% (respectively) at 5-10 
years in mature surgical series (6, 7). Surgical cure of patients with clinically 
organ-confined (T1-T2) cancer (as evidenced by an undetectable PSA at 5 years) 
is related to the grade (Gleason score), PSA, pathologic stage (pT1-2, versus pT3 
or positive lymph nodes) and surgical margin status of the cancer (6-10). Patients 
with well differentiated (Gleason score 2-6), organ-confined cancers with a serum 
PSA of less than 10 ng/ml, can expect an 83-95% freedom from any relapse over 
a five-year period (7). Alternatively, patients with a preoperative PSA >20 ng/ml, 
Gleason score >8, seminal vesicle involvement, extensive positive surgical 
margins, or lymph node involvement have at least a 50 percent chance of 
biochemical relapse within 5 years (7-10).  Of interest, many of these criteria also 
identify subsets of patients at risk for failure of definitive external beam radiation 


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therapy (11). Thus, patients at “high” risk for failure with standard local therapies 
can be stratified by the above clinicopathologic variables. 
 
Of these variables, the presence of pelvic lymph node involvement at the time of 
radical prostatectomy is the most adverse and is virtually synonymous with 
systemic disease as 85% of surgically treated patients have either a rising PSA or 
distant metastasis by 5 years (12). As such, systemic therapy with hormonal 
ablation is routinely initiated (with or without local therapy) and has been shown 
to result in a substantial increase in the interval to progression (13). The results of 
recent nonrandomized retrospective studies suggest that the further addition of 
local control (with radical prostatectomy or external beam radiotherapy) together 
with early hormonal ablation may represent a therapeutic advance in patients with 
limited regional metastases (14, 15).  Messing et al have shown that adjuvant long 
term hormonal therapy instituted immediately after RP (in those patients with 
microscopic lymph node metastases) is associated with improved survival when 
compared to surgery alone with delayed hormonal therapy (16) 
 
The optimal management of surgically treated patients with negative lymph nodes 
(at surgery), but who remain at high risk for clinical or biochemical failure 
(Gleason score >8, seminal vesicle involvement, extensive positive surgical 
margins) remains problematic. Data from two recent series from Johns Hopkins 
and the Mayo Clinic revealed that in this cohort of men, the 5-year disease free 
survival ranged from 44-49% (17-18). A more recent series from M.D. Anderson 
Cancer Center noted a higher 5-year disease free survival (68%), which may be 
related to the higher incidence of organ and specimen confined high grade 
cancers. (19)  In a recent series of 2404 men that underwent radical prostatectomy, 
it was noted that the sites of relapse were distant (33%), local (9%), and rising 
PSA only in 58% of men (17). Adjuvant radiation therapy in this setting would 
only 
potentially 
benefit 
a 
subset 
and 
would 
not 
address 
systemic 
“micrometastases” which may contribute to biochemical failure.  In fact, two 
studies suggest that of patients undergoing adjuvant radiation therapy post-
prostatectomy in the setting of positive seminal vesicles or high grade disease only 
37-45% are free from relapse at five years, suggesting little beneficial effect (20-
21). The primary objective of the current protocol is to determine if one year of 
adjuvant hormonal ablation (which possesses local and systemic antitumor 
effects) in node negative radical prostatectomy patients at high risk for 
progression will result in an improvement in disease-free survival at five years.  
 
Hormonal ablation will be accomplished by administration of the luteinizing 
hormone releasing hormone agonist (LH-RH) Goserelin (Zoladex) in 
combination with the nonsteroidal antiandrogen  Bicalutamide (Casodex) to 
produce total androgen blockade. Total androgen blockade is routinely utilized in 
the clinical management of prostate cancer patients.  The rationale is based on 
lowering serum testosterone levels into the castrate range utilizing either 
orchiectomy or an LH-RH agonist.  An antiandrogen is added to negate the effects 
of adrenal androgens by competitively binding to the androgen receptor.  In three 
large early clinical trials total androgen ablation was shown to prolong 
progression free and over all survival by 3-12 months and 7 months respectively 
(22-24).  However, patients with minimal metastatic disease were noted to receive 
the most benefit. Recently, the magnitude of the clinical benefit of total androgen 


Protocol ID97-077 
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blockade has been questioned. A collaborative mega-analysis of 27 randomized 
trials involving 8,275 men (98% of those were randomized in trials of total 
androgen blockade versus monotherapy) revealed an overall 5 year survival 
benefit of only 2-3% (25). Among such trials, the randomized study of 
orchiectomy and flutamide versus orchiectomy alone (NCI-INT-0105) revealed no 
survival benefit for the antiandrogen cohort when patients underwent surgical 
castration.(26). These results were significantly different than those obtained 
when the mode of androgen suppression used in prior randomized trial was an 
LH-RH agonist (22). Thus current opinion favors the fact that an antiandrogen 
blocks the testosterone "flare" phenomenon and probably makes the LH-RH 
agonist a safer drug. However, when orchiectomy is used for testosterone 
suppression an antiandrogen is probably unnecessary. 
 
Total androgen blockade has been evaluated in conjunction with radical 
prostatectomy in the neoadjuvant setting. For such patients, reversible androgen 
suppression (i.e., nonsurgical castration) is the optimal approach.  Several 
randomized studies initially reported a decrease in the incidence of positive 
surgical margins with three months of neoadjuvant hormonal therapy in 
“clinically” confined prostate cancer. (27-29).  However, with long term follow-
up there has been no improvement in disease free survival using the three month 
neoadjuvant hormonal therapy approach. (30) With regards to the timing of 
androgen ablation, a recent study by Gleave et al. suggested that 8 months of neo-
adjuvant androgen ablation (compared with 3 months) resulted in an optimal PSA 
nadir prior to surgery (31)  A follow-up randomized prospective evaluation of 
three versus 8 months of androgen ablation prior to RP has shown an initial 
benefit with respect to PSA nadir, prostate volume and positive surgical margins 
in favor of 8 months of therapy (32). If the enhanced nadir PSA values and 
negative surgical margins were reflective of enhanced tumor destruction, then 
perhaps longer periods of androgen ablation may be advantageous. This type of 
data provides a rationale to prospectively define the effect of one year of adjuvant 
hormonal therapy post radical prostatectomy. It is hypothesized that a proportion 
of "high risk" patients will exhibit residual prostate cancer cells that are 
predominantly androgen sensitive and that one year of therapy will be adequate 
therapy to induce cell death in this population. 
 
Total androgen ablation as an adjuvant treatment in lymph node negative radical 
prostatectomy patients has not been studied in a prospective randomized fashion.  
In addition, the optimal duration of therapy is also unknown. Several prospective 
randomized studies in patients receiving adjuvant androgen ablation subsequent to 
external beam radiation therapy have found that the incidence of local, distant, 
and biochemical failure was significantly decreased when compared with patients 
receiving delayed hormonal ablation at relapse subsequent to radiation therapy 
(33). Further, survival in patients with high Gleason grade cancers was enhanced 
at five years (33-35). Whether the same data would be obtained in a radical 
prostatectomy population is unknown and needs to be assessed. Preliminary data 
from the Casodex Early Prostate Cancer program are encouraging in this regard 
(36). A total of 3603 men received 150mg Casodex (high dose anti androgen) or 
placebo orally as an adjuvant after RP or radiotherapy or as primary therapy 
versus placebo in those not receiving definitive therapy. At a median follow-up of 


Protocol ID97-077 
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2.6 years, adjuvant monotherapy with Casodex reduced the incidence of objective 
progression by 43% (16 versus 10%, p <0.0001 [36]). 
 
Thus the proposed study will expand our knowledge base, with respect to the 
efficacy of a defined period of total androgen blockade in patients at risk for 
failure due to microscopic local or distant disease post RP. The study is timely in 
that there is no consensus on the optimal therapy (or its duration) in patients with 
adverse pathology post radical prostatectomy. 
  
The third and fourth study objectives will be to conduct a companion quality of 
life study.  We will assess the quality of life in patients during and following such 
treatment utilizing the Medical Outcomes Study 36-Item Short Form Health 
Survey (SF-36) (37), the Profile of Mood States (POMS) (38), the UCLA Sexual 
Functioning Scale (39), the Dyadic Adjustment Scale (40), and the Southwest 
Oncology Group (SWOG) Treatment Specific Symptom Checklist, developed for 
the flutamide trial.  We also will assess patient preferences (utilities) for treatment 
outcomes related to androgen ablation, and conduct a quality of life study among 
the wives/partners of trial participants. 
 
2.1 
Androgen ablation in prostate cancer patients and quality of life   
 
The quality of life component of this study is critical.  Patient quality of 
life is increasingly considered an important outcome measure in clinical 
cancer control studies (41). To date, the effect of androgen ablation on the 
quality of life of relatively healthy men (i.e., men who do not have 
metastatic disease) is not well studied. The side effects of androgen 
ablation therapy may have considerable quality of life implications -- 
impotence and loss of libido, for example, hot flashes, breast enlargement 
and tenderness, and feminine distribution of fat deposits (42-44). Herr et 
al. (45) studied men with asymptomatic, metastatic prostate cancer who 
chose either androgen ablation or watchful waiting.  At six months, they 
found that those who chose androgen ablation had more sexual 
dysfunction (problems with erection and interest and enjoyment of sex), 
physical symptoms (including urinary problems, hot flashes, appetite, 
nausea and vomiting, sleep, and breast enlargement), and fatigue than men 
who chose no therapy.  The groups did not differ in other dimensions of 
quality of life. Kornblith et al. (46) surveyed a convenience sample of men 
with prostate cancer: 14  (late and early-stage disease) had received no 
treatment, 35 (earlier stage disease) had had prostatectomy or radiation 
only, and 61 (later stage disease) had received hormonal therapy.  A 
multivariate analysis of variance found an overall significant difference 
across all dependent measures, with the hormonal therapy groups reporting 
the worst quality of life.  According to the univariate analysis, the groups 
differed significantly on physical functioning, physical symptoms, and 
sexual problems.  Differences in fatigue, psychological distress, and 
impact on family/social life were not significant in the univariate analysis, 
but scores were worse in the hormonal therapy group. Studies of different 
forms of androgen ablation generally show that patients experience 
decreases in sexual functioning and marital satisfaction with some 
improvement in symptoms and overall quality of life (47,48).  


Protocol ID97-077 
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The current literature on quality of life and androgen ablation is limited by 
the use of non-randomized designs, nonstandardized measures (especially 
to measure marital and sexual functioning), small sample sizes, and an 
exclusive focus on men with advanced disease.  This randomized trial 
provides us with a unique opportunity to document the effects of early 
androgen ablation on quality of life.  We will use well-validated quality of 
life measures to assess the life functions that we expect to be most affected 
by the hormonal therapy: sexual functioning, fatigue, emotional well-
being, physical functioning, and treatment-specific symptoms.  However, 
because so little is known about the effect of hormonal therapy on the 
quality of life of men with local disease, we will monitor other dimensions 
of quality of life to learn whether they are affected by the treatment as 
well. 
 
2.3 
Quality of life of patients’ wives/partners 
 
We will also study the quality of life of the patients’ wives and partners* 
because wives are likely to be the primary caregivers of men with prostate 
cancer.  The stress of caregiving may significantly affect their quality of 
life and emotional well being; this is also true for the side effects 
associated with androgen ablation (e.g., decreased sexual functioning). 
 
Caregiving constitutes a chronic stressor independent of the diagnostic 
category of the patient (54-56); the evidence is strong that caregiving can 
have many negative effects on the caregiver, including the development of 
sleep disturbances, anxiety, depression, and a sense of helplessness 
(54,55,57). The current shift away from inpatient treatment and toward 
shorter hospitalization has placed even greater responsibility on family 
caregivers.  There is evidence, moreover, that some cancer patients’ 
spouses may be more emotionally distressed than the patients and remain 
so for even longer than the patients (46, 58-60). Frequently, the spouse’s 
distress level is related to the seriousness of the patient’s condition (61-
65).  
 
When a patient experiences side effects from androgen ablation therapy, it 
can influence the quality of life of his wife as well.  The patient’s lack of 
sexual desire and impotence will affect the sexual life of the wife, and the 
couple’s sexual problems may lead to or aggravate marital discord.  The 
literature suggests that assessing sexual functioning of cancer patients 
only, and not their partners, provides an incomplete picture (42). Fatigue 
resulting from a patient’s treatment may increase the burden on the wife 
for caregiving and household tasks, and it may affect the couple’s social 
contact. Kornblith et al. (46) found that the patients’ symptoms, 
particularly fatigue and urinary frequency, were significantly correlated 
with the wives’ quality of life. 
 
                                                          
* We will use the term wives to refer to this group, although female partners who have had 
an intimate relationship with the patient for more than 2 years will be included as well. 


Protocol ID97-077 
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Previous approaches to evaluating spousal influence on the patient’s 
quality of life have not reflected the dyadic nature of the behavioral 
process (46,53,66). The focus has been on the patient or on the spouse, 
rather than on both simultaneously.  Dyadic interaction models (67-69) 
account for the dynamic nature of the couple's relationship, in which, for 
example, one member’s quality of life influences the quality of life of the 
other.  The direction of the influence, termed dominance, provides 
information about the interplay between spouses in the marital 
relationship.  Direct dominance is exhibited in a relationship if the 
behavior or feelings of one member of the couple predicts the future 
behavior or feelings of the other.  We expect that a patient’s 
symptomatology will directly influence the psychological well being of his 
wife. Indirect dominance refers to the situation in which the behavior or 
feelings of one member of the couple predicts the couple’s future 
interactions.  The study will examine the couple as an interacting unit with 
varying degrees and directions of influence.  Direct dominance and 
indirect dominance will be evaluated for each aspect of quality of life that 
is measured.  The possibility that different levels of dominance occur as a 
result of the treatment the patient is receiving will be investigated. 
 
3.0   Background Drug Information and Adverse Events 
 
Goserelin Acetate  (Zoladex) contains a potent synthetic decapeptide analogue of 
luteinizing hormone releasing hormone (LHRH) analogue.  Zoladex 10.8mg 
implant is supplied as a sterile biodegradeable product containing Goserelin 
acetate equivalent to 10.8mg of Goserelin. It is designed for subcutaneous 
administration with a continuous release over a 12-week period. (70) 
Following administration, Zoladex causes an initial increase in serum luteinizing 
hormone and follicle stimulating hormone levels. With subsequent increases in 
serum testosterone. Chronic administration of Zoladex leads to sustained 
suppression of pituitary gonadotropins, and serum levels of testosterone 
consequently fall into the range normally seen in castrated men. 
Leuprolide is a synthetic nonapeptide analogue of LH-RH that inhibits pituitary 
gonadotropin secretion. Leuprolide administration causes an initial increase in 
gonadotropin secretion and serum testosterone levels, however, serum 
testosterone levels fall over a 2-4 week period into the range seen in surgically 
castrated patients.  Both long term endocrine and objective tumor responses are 
similar in advanced prostate cancer patients treated with either orchiectomy or 
Leuprolide (70).   
Bicalutamide is an orally active nonsteriodal antiandrogen with negligible 
gastrointestinal intolerance and the convenience of once-daily dosing (71-72). 
The most frequent adverse event noted for patients with metastatic prostate cancer 
treated with the combination of a LH-RH analogue and an antiandrogen has been 
hot flashes (49%).  Other adverse events occurring in 10% of these patients 
included abnormal liver function tests, nocturia, diarrhea, nausea, pain and 
constipation (71).  In a recently reported multicenter trial, diarrhea was the most 
frequently reported adverse experience leading to treatment withdrawal and 
occurred in 6% of patients receiving flutamide in combination with an LH-RH 
agonist (72). This same side effect occurred in only 0.5% of patients when 
bicalutamide was used as the antiandrogen (72).  Life threatening flutamide-


Protocol ID97-077 
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associated hepatotoxicity has been reported at a rate of approximately 3/10,000 
patients (70,73).  It is recommended that liver function tests be monitored and if 
elevated to 2x normal value in the absence of other reasons that the antiandrogen 
be discontinued. Hepatotoxicity is usually reversible in this setting.  Occasionally 
prolongation of prothrombin times have been noted in patients receiving warfarin 
therapy after flutamide is initiated. Thus, in this setting prothrombin times should 
be routinely monitored. Similar precautions are also advised when bicalutamide is 
administered.  (See Appendix D for additional pharmaceutical details on 
Goserelin and  bicalutamide). 
Based upon the final analysis of the double blind trial that compared an LH-RH 
(Goserelin or Leuprolide) together with either bicalutamide or flutamide, there 
was no significant difference in either time to progression or survival for either 
regimen, however, the bicalutamide group had less treatment withdrawal due to 
diarrhea (72). 
 
4.0  
Patient Eligibility 
 
 
4.1 
Clinical Trial 
 
 
 
4.1.1 Organ confined prostate cancer subsequent to clinical staging (T1- 
 
 
 
T2C). 
 
4.1.2 Radical prostatectomy, bilateral pelvic lymph node dissection 
performed. 
 
4.1.3. Patients may have received up to 3 months of reversible androgen 
ablation prior to radical prostatectomy (i. e, no surgical castration).  
 
 
 
 
4.1.4  Pathologic assessment of surgical specimens by M. D. Anderson  
 
 
 
Cancer Center pathologist.   
 
4.1.4a The M. D. Anderson pathologist will review the prostatectomy 
specimen including the pelvic lymph nodes.  For patients who received 
androgen ablation prior to the prostatectomy the pre-treatment biopsy 
will also be evaluated to determine the Gleason score. 
 


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All stained sections from the radical prostatectomy specimen including 
pelvic lymph nodes and the appropriate institutional pathology reports 
should be submitted.  The material submitted should also include any 
special stains performed.  If the patient received pre – op hormonal 
ablation therapy, all the slides from the pretreatment biopsy should 
also be submitted to the review center.  In addition, a representative 
block of the tumor and a block of normal prostate from the 
prostatectomy specimen should be included.  For patients treated pre-
operatively with hormonal ablation a block of tumor and a block of 
normal tissue from the pre-treatment biopsy should also be submitted.  
The slides will be returned to the submitting institution.  The blocks 
will be retained at M. D. Anderson for the future evaluation of markers 
of progression. 
 
If the blocks received are not considered representative of the tumor, 
different block/s will be requested of the contributing pathologist and 
the originally received block/s will be returned upon receipt of the new 
block/s. 
 
  
 
Note: The blocks of tumor should be representative of the tumor with 
the highest histologic grade. 
 
4.1.4b  Slides, blocks and pathology report/s should be sent to the MDACC 
within 48 hours of registration via overnight express to: 
 
MD Anderson Cancer Center 
Data Management Center 
1100 Holcombe Blvd-Rm  3.100 
Houston, TX  77030 
 
 
 
 
 
 
 
 
 
 
4.1.4c Pathologic data will be recorded on the attached report form. 
A copy of the completed report form will be sent to the contributing 
pathologist. 
 
 
 
4.1.4d Pathologic criteria for eligibility include: 
 
 
 
 
For patients with (up to 3 months) prior androgen ablation: 
  
 a) 
Gleason score  8 on pretreatment biopsy, (or) 
  
 b) 
Seminal vesicle invasion, (or) 
  
 c) 
Pretreatment biopsy Gleason score  7 and extraprostatic 
 extension with positive surgical margins in prostatectomy 
specimen. 
 
 
 
Note: 
Patients treated with androgen ablation prior to surgery will 
 
 
have the pre-treatment biopsy reviewed.  The Gleason score 
from the biopsy will be the one considered for inclusion in the 
study. 
 


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For patients without prior androgen ablation: 
 
  a) Gleason grade sum score  8 on radical prostatectomy specimen, 
(or) 
 
  b) Seminal vesicle invasion regardless of grade, (or) 
 
  c) Extraprostatic extension and positive surgical margins and Gleason 
sum  7. 
 
4.1.5 Radical prostatectomy performed within 90 days of enrollment and           
serum PSA level  < 0.1ng/ml prior to enrollment. 
 
Please Note: 
Some laboratories only report a value as low as 0.2 ng/ml.  
Therefore, they consider a value of less than 0.2ng/ml as 
undetectable. Only PSA values of less than 0.1ng/ml will be 
considered undetectable for this study. Some laboratories have 
agreed to send out serum samples to labs that offer a lower level of 
sensitivity. For example, Quest laboratory has agreed to send the 
samples to Dianon for an ultrasensitive PSA assay. This is easily 
performed by writing “Ultrasensitive PSA by Dianon- test code 
#36448” on the Quest requisition. Please check with your local lab 
to determine their lower limit of sensitivity for the serum PSA 
assay.  
 
 
 
 
i. 
Written informed consent 
 
ii. 
Criteria for Participating Urologists 
Only those urologists who have completed at least a one year 
clinical fellowship in urologic oncology (certificate must be on 
file) may accrue patients to this study. 
 
 
4.2. 
Substudy on wives’/partners’ quality of life 
 
 
4.2.1 Must have been in an intimate relationship with the trial participant 
for at least 2 years prior to the participant’s enrollment in the 
clinical trial. 
 
4.2.2 Must be female. 
 
 
4.2.3 Verbally consents to participate in the partner QOL substudy. 


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5.0  
Exclusion Criteria 
 
 
5.1   
Any evidence of metastatic disease confirmed prior to enrollment. 
 
5.2 
Inability to confirm pathologic risk factors or inadequate prostatectomy 
(see item 4.1.5). 
 
5.3 
Hormonal ablation for greater than 3 months or radiotherapy for prostate 
cancer. 
 
5.4  
Failure to achieve prostate specific antigen level of less than 0.1ng/ml 
prior to enrollment in study. 
 
 
5.5   
Elevation of liver function tests 2x normal. 
 
 
5.6   
Contraindication to the use of LH-RH agonists or antiandrogens. 
 
5.7   
Active secondary malignancy (other than squamous or basal cell skin 
cancer) within five years prior to enrollment in study. 
 
5.8   
Any concomitant medical condition that would make it undesirable for the 
patient to participate in the trial or jeopardize compliance with the 
protocol. 
 
6.0  
Pretreatment Evaluation 
 
b. 
Complete history and physical examination within 90 days of enrollment. 
 
c. 
Liver function tests (i.e. total bilirubin, AST, ALT, ALK phosphatase), 
PSA, prothrombin time (if on Coumadin) within days 90 of enrollment. 
 
d. 
Specimen for Research 
 
Specimen Preparation: Labeling and Submission 
 One red top (10cc) tube is needed 
 10cc of blood is drawn from the patient and placed in a red top tube. 
 Blood is allowed to clot. 
 Centrifuge for 15 minutes to separate serum cells. 
 Transfer a minimum of 1.0 cc of serum to a polypropylene vial. 
 Label the sample with the patient I. D., study number, date drawn, and 
label the tube “research specimen”. 
 Immediately freeze at –70 degrees C.  Serum samples may be saved 
and sent in batches as long as they are maintained at – 70 degrees C.  
The samples must be mailed to the MDACC DMC within 1 year of 
registration.  
 Complete the specimen transmittal form.  One original must 
accompany the specimen.  A copy is submitted as general data 
submission. 


Protocol ID97-077 
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 Plan mailing so that the specimens do not arrive after 2:00 p.m. (CST) 
Monday through Friday and not on Saturday or Sunday and/or 
MDACC holidays. 
 Mail the specimen on dry ice via overnight express (Federal Express or 
UPS) to: 
 
THE UNIVERSITY OF TEXAS 
M. D. ANDERSON CANCER CENTER 
DATA MANAGEMENT CENTER 
1100 HOLCOMBE BLVD. – ROOM 3.100 
HOUSTON, TEXAS 77030 
 
 The specimen must be packaged to avoid breakage, spillage, and other 
contamination.  
 For specimen submission questions, call the MDACC Data 
Management Center at 713/792-8519. 
 These specimens will be sent by the MDACC DMC to the Tumor 
Marker Lab room B4.4351 for processing and storage. 
 
e. 
Bone scan- required if PSA>10 ng/ml prior to surgery. If not performed 
preoperatively must obtain prior to enrollment (< 90 days post surgery). 
 
f. 
Pathology consult from M. D. Anderson Cancer Center study pathologist 
(if surgery performed elsewhere). 
 
g. 
Patient quality of life measures – Dr. Basen-Engquist and staff of the 
MDACC Department of Behavioral Science will conduct a telephone 
interview after registration and before treatment with the patient that 
includes Medical Outcomes Study 36-Item.  Short Form Health Survey 
(SF-36) (37), the Profile of Mood States (POMS) (38), UCLA Sexual 
Functioning Scale (39), the Dyadic Adjustment Scale (40), and the 
Southwest Oncology Group (SWOG) Treatment Specific Symptom 
Checklist.  Patient preference data will also be collected at this time.  
Psychometric information about these questionnaires is provided in 
Appendix B. 
 
h. 
Wife/partner quality of life measures –Dr. Basen-Engquist and staff of the 
MDACC Department of Behavioral Sciences will conduct a telephone 
interview after registration and before treatment with the wife/partner that 
includes Medical Outcomes Study 36-Item Short Form Health Survey (SF-
36) (37), the Profile of Mood States (POMS) (38), UCLA Sexual 
Functioning Scale (adapted) (39), the Dyadic Adjustment Scale (40). 
 


Protocol ID97-077 
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2. Registration/Randomization Procedure  
 
 
7.1 
All Extramural Collaborators will register patients by calling the MDACC 
Data Management Center between 8 am – 5 pm CST, Monday-Friday. This 
will allow the MDACC DMC to input these institutions and physicians into 
the computerized database. IRB approval will be verified and the eligibility 
checklist will be reviewed. A confirmation of registration and a reminder 
letter to forward pathology slides will be mailed to the Extramural 
Collaborator.  A copy of the registration confirmation will be forwarded to 
the Department of Behavioral Science with the telephone number of the 
patient by the MDACC DMC. 
 
7.2 
After the pathology slides have been sent to the MDACC DMC and 
confirmed to be appropriate for randomization by the MDACC pathologist, 
the registering institution will be notified as to the patient’s eligibility for 
randomization by the MDACC DMC.  A patient may be randomized up to 3 
weeks after registration.  All Extramural at (713) 792-8519 between 8 am – 5 
pm CST, Monday-Friday.  A randomization checklist will be reviewed and 
patients will be stratified by the following criteria: 
 
 
 
 
 
MDACC participants  
vs 
Extramural Collaborators 
 
 
 
 
Pathologic Stage: 
 
 
 
 
Organ confined 
 
vs 
Other 
 
 
 
 
Seminal vesicle 
 
vs 
Other 
 
 
 
 
Margin status: 
 
 
 
 
Positive 
 
 
vs 
Negative 
 
 
 
 
Pre prostatectomy PSA level: 
 
 
 
 
PSA  10 ng/ml 
 
vs 
PSA > 10 ng/ml 
 
 
 
 
Neoadjuvant Hormonal 
 
 
 
 
Therapy 
 
 
vs 
None 
  
A confirmation of randomization letter will be mailed to the participating 
institution/affiliate or Extramural Collaborators.  Therapy must start within 
10 days of randomization. 
 
 
8.0 Treatment Plan 
 
 
Subsequent to pretreatment evaluation and randomization, patients on arm A 
receive  Goserelin 10.8 mg sc every 12 weeks (+/- 1 week) in addition to 
Bicalutamide 50 mg daily.  The total treatment period for patients on Arm A 
will be one year.  Patients on Arm B receive no initial treatment.  At the time 
of relapse, patients in Study Arms A and B will receive additional therapy 
according to the clinical judgment of their physicians 
 
Arm A - 165 patients - Goserelin + Bicalutamide (one year) 
 
 
 
Arm B - 165 patients - No initial treatment 
 


Protocol ID97-077 
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Treatment at relapse - Physician preference 
 
9.0  Evaluation During Study (See Treatment Plan) 
 
a. 
Arm A - Liver test 1, 2, 3, 6, 9, 12 months after initiating therapy. Solicitation 
of adverse events, physical examination, serum PSA, every three months (3-
12 mos; +/- 2 weeks). Serum PSA, with physical examination every 6 months 
(mos. 13-60; +/- 1 month). Then yearly serum PSA and physical examination 
(> 60 mos. - 120 mos; +/- 1 month) or until biochemical or clinical 
progression. Patient’s requiring Coumadin anticoagulation will have 
prothrombin time monitored at least every 3 months (+/- 2 weeks) and as 
necessary to adjust medication. For patients exhibiting disease progression (at 
anytime during study), physical examination and serum PSA tests will occur 
at a minimum of 12 month (+/- 1 month) intervals for the duration of the 
study (see section 10.0 also). 
 
Arm B - Liver function tests are not required for patients that are not 
receiving antiandrogen therapy.  All other testing procedures and intervals are 
the same as Arm A. 
 
b. 
Imaging studies will be obtained as clinically indicated. 
 
c. 
Quality of life will be assessed by the SF-36 questionnaire (37), the POMS 
(38), the UCLA Sexual Functioning Scale (39), the Dyadic Adjustment Scale 
(40), and the Southwest Oncology Group Treatment Specific Symptoms 
checklist.  Quality of life will be assessed at entry into the study as well as at 6 
month intervals during years one and two of the study, and at one year 
intervals up until month 60.  Quality of life questionnaire data will be 
collected by telephone interview.  The interviews will last approximately 30-
40 minutes. Before the interview takes place, we will contact patients to 
schedule a time for the interview.  We also will send a copy of the interview 
questionnaire for patients to refer to during the interview.  Patients will 
receive a small gift (worth about $10) for each quality of life interview they 
complete. 
 
In order to include Spanish speaking patients and their wives/partners in the QOL 
companion study, we will use Spanish versions of those questionnaires that have 
been translated, translate the questionnaires for which translations do not exist.  
The method for translation will include translating the questionnaire from English 
to Spanish, then having a different translator translate from Spanish back to 
English to determine if the appropriate meaning has been maintained.  The 
translated questionnaire also will be reviewed and pilot-tested by Spanish-
speaking individuals in focus groups. 
  
All quality of life data will be collected by M. D. Anderson personnel. 
 
d. Wives/partners of trial participants will complete quality of life assessments every 
six months for the first two years of the study.  The names and contact 
information of the wives/partners will be obtained from the patient when his 
baseline QOL interview is scheduled.  Within three weeks of their husband’s 


Protocol ID97-077 
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enrollment in the trial, we will send a letter to the wives/partners explaining the 
purpose of the trial and what data will be collected.  This will be followed by a 
telephone call in which we will reiterate the information supplied in the letter, 
obtain their verbal consent, and schedule the first telephone interview.  The 
subsequent data will be collected using telephone interviews as well. 
Wives/partners of the trial participants will complete the same instruments as the 
trial participants, with two exceptions.  They will not complete the treatment-
related symptoms checklist, and they will complete a modification of the UCLA 
Sexual Functioning scale that excludes the items about erections.  The women 
will receive a small gift (worth about $10) for each interview they complete. The 
data collection for the wives/partners substudy will be done by M. D. Anderson 
personnel. 
 
10.0  Criteria For Progression  
 
 
 
10.1 Criteria 
 
  
a.  Two successive rises in serum PSA beginning at a threshold value of 0.1 ng/ml 
or any single value  0.5 ng/ml. For PSA values between 0.1-0.4 ng/ml serum 
levels should be repeated at 3-month intervals to document the detectable level 
and to confirm a second rise. The date of documentation of the second increase 
is the recorded date of progression. For patients presenting with an initial PSA 
increase of  0.5 ng/ml, a repeat serum PSA level should be obtained prior to 
one month to confirm and document progression.  The date of confirmation is 
the recorded date of progression. 
 
 
b. In absence of above, biopsy proven recurrence. 
 
 
 
 
10.2 Evaluation of disease recurrence 
 
 
Subsequent to documentation of a rising PSA by the above criteria and prior to 
the institution of primary (Arm B patients at relapse) or secondary therapy (Arm 
A patients), patients may  undergo some of the following evaluations as 
determined by the attending physician as clinically indicated:*  
 
 
a. complete history and physical examination 
 
b. bone scan 
 
c. CT scan or MRI of abdomen and pelvis 
 
d. transrectal ultrasound with biopsies of suspicious areas as well as the 
urethrovesical anastomosis 
 
 
*Represents suggested disease evaluation- other tests should be ordered as 
clinically indicated. 
 
 
11.0  Criteria for Removal from Study 
 
 
11.1 Patient request 
 
 


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The patient gives verbal and/or written notification declining further 
participation in the study. The patient will be taken off study and data will be 
censored after the last follow up. 
. 
11.2 Lost to Follow Up 
 
The patient will be considered lost to follow up when a scheduled study follow 
up is missed and the patient cannot be contacted via a minimum of one certified 
letter and two telephone calls. If there is no response to certified mail within one 
month of the mailing date and the telephone calls are unanswered, the patient 
will be taken off study. Their data will be censored after the last documented 
follow up. 
 
12.0 
Protocol Deviation* 
 
 
 
12.1  Noncompliance with medication (arm A). The use of non protocol   
 
 
 
compounds known to affect serum testosterone levels or have  
 
 
 
 
antiandrogenic action (arm A, B, i.e., finasteride, Saw Palmetto, etc.) prior 
 
 
 
 
to objective evidence of failure 
 
 
12.2  Use of nonprotocol adjuvant therapies (i.e., radiation) prior to evidence of   
 
progression. 
 
 
12.3 
Adverse event requiring cessation of therapy (severe event or elevation of 
liver function tests 2x normal). 
 
 
12.4  Investigator feels it is in patient’s best interest to discontinue therapy. 
 
* Patients in the above categories (12.1-12.4) will have protocol deviations noted 
in the database. It will state type of deviation, date of deviation, status of patient, 
and whether patient is on study or off study.  They will be followed throughout the 
course of the study and data will be analyzed on an intent to treat basis as well as a 
secondary analysis as to the actual treatment received. 
 
Patients requiring the discontinuation of bicalutamide due to elevation of liver 
function tests or inability to tolerate the antiandrogen (due to nausea or diarrhea) 
will be offered other commercially available antiandrogens.  Alternatively, should 
they refuse they may continue on study receiving a LH-RH agonist as 
monotherapy. 
 
13.0   Statistical Considerations  
 
13.1 
Objective 1.1 
 
Recent series have reported 5 year disease free survival ranging from 44-68% 
among cohorts of patients with Gleason  8 prostate cancer, seminal vesicle 
invasion, or those with Gleason score 7 prostate cancer and extraprostatic 
extension of cancer with positive surgical margins (17-19). Considering the 
heterogeneity of results, we have assumed that patients randomized to arm B have 
at least a 35% rate of clinical or biochemical progression over five years. We 


Protocol ID97-077 
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hypothesize that patients treated in an adjuvant setting (arm A) will exhibit a 
decrease in the recurrence rate to 20% over the same time period. To detect this 
15% difference with a p < 0.05 and a statistical power of 90%, approximately 150 
patients would need to be entered on each arm of the study (ST PLAN software). 
To account for a 10% drop-out rate, 30 additional patients would be randomized. 
Thus, 330 patients are anticipated to be randomized on this study.  Results will be 
analyzed on an intent to treat basis and stratified for patients enrolled at M. D. 
Anderson versus extramural sites. In addition, patients will be stratified for the 
following Pathologic factors: pathologic stage - organ confined versus other, 
seminal vesicle involvement versus other, Margin status - positive versus negative 
Pre-prostatectomy PSA level 10 ng/ml versus >10 ng/ml. Data will be analyzed 
according to Kaplan-Meier/Cox methodology stratifying for the above variables. 
A separate analysis for efficacy and safety will be performed for patients treated 
with  bicalutamide and lueprolide versus those receiving flutamide and lueprolide. 
 
Although not specified as objectives of the study, patients will be followed for ten 
years to determine the incidence of androgen independent disease, disease 
specific, and overall. The study assumes that 33 of 165 patients randomized to 
Arm A, and 58 of 165 patients randomized to Arm B will fail within five years.  
Patients exhibiting clinical or biochemical evidence of failure will eventually be 
treated with hormonal ablative agents in an attempt to control the disease. The 
study assumes that other treatments could also be utilized (local radiation) by 
treating physicians, but that no curative therapy will become available during the 
study. In addition, the study assumes that the distribution of treatments between 
study arms will be similar. Thus the study would continue to have the power to 
detect a 15% difference between either study arm A or B for these endpoints with 
90% power if the intercurrent death and drop-out rate does not exceed 10%. The 
study retains an 80% power to detect such a difference as long as the incidence of 
death from other causes or patient drop out does not exceed 35%. 
 
 
13.2 
Objective 1.2-1.3 
 
Primary quality of life outcomes of this study are patient scores on the five quality 
of life measures, including physical function, emotional well-being, fatigue, 
sexuality, and treatment-specific symptoms. We will test for differences in the 
quality of life measures between the two patient groups using two-sided t-tests. 
Since there are five quality of life measures, the level of each test will be adjusted 
using a Bonferroni correction to preserve an overall type I error rate of 0.05 at 
each follow-up time point.  For each test we will therefore use a level of  = 0.01 
(i.e., 0.01 = 0.05/5).  To estimate power, we will use what Cohen (74) called an 
“effect size index,” in which the detectable difference between two groups is 
given in terms of the population standard deviation units. For example, an effect 
size index of 0.25 represents a detectable difference between two groups equal to 
0.25 standard deviation units. Assuming that the quality of life companion study 
will have a higher dropout rate than the clinical trial (15% rather than 10%) we are 
estimating that 174 patients per treatment arm would be available for the quality 
of life analysis.  At a level of  = 0.01, we will have 80% power to detect a 
difference of 0.37 standard deviation units.  Given the assumption that 76% of the 


Protocol ID97-077 
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men enrolling in the study will be married or have steady partners (based on 
census data) and that 80% of the partners will participate in the study, we estimate 
that 132 wives/partners will be included in each study arm.  At a level of  = 0.01, 
we will have 80% power to detect a difference of 0.43 standard deviation units.  
Cohen (74) describes effect size values of 0.25 as being “small,” values of 0.50 as 
being “medium,” and values of 0.80 as being “large.”  
 
13.2.1 Statistical analyses of primary quality of life hypotheses 
 
Hypothesis 1.1: A significant treatment arm-by-time interaction will be 
found, indicating that the quality of life of patients in the androgen 
ablation arm will be poorer than that of the control arm patients during and 
shortly after androgen ablation, and but better than patients in the control 
arm at the 2 to 5 year assessments.  
Hypothesis 1.2: A significant treatment arm-by-time interaction will be 
found, indicating that the quality of life of wives/partners of patients in 
androgen ablation arm will be poorer than that of the wives/partners of 
control arm patients during and shortly after patients’ androgen ablation, 
but better than wives/partners of patients in the control arm at the 2 year 
assessment. 
Descriptive statistics (e.g., means, ranges, standard deviations) will be computed 
for the quality of life scores at each time point for each of the two groups. Ninety-
five percent confidence intervals will be constructed for each of the means. 
Graphic methods (e.g., boxplots and histograms) will also be employed to closely 
examine the distributions of the quality of life scores at each time point. Bivariate 
associations between quality of life and selected demographic and disease-related 
variables, including age, socioeconomic status, ethnicity, time since diagnosis, 
and duration of treatment will be evaluated using Pearson’s product-moment 
correlation coefficients together with scatterplots where appropriate. 
 
We will test for differences in the quality of life measures between the two patient 
groups using two-sided t-tests at  = 0.01 to preserve the overall type I error rate 
of  = 0.05.  Although the randomization procedure insures the validity of the t-
tests, additional analyses will be conducted using linear regression analyses.  In 
these analyses, each quality of life measure will be regressed onto treatment 
condition and several potential confounders, including baseline quality of life, 
age, ethnicity, and socioeconomic status.  Potential pairwise interactions between 
the treatment condition and the confounders also will be evaluated.  This portion 
of the modeling allows us to explore whether the treatment affects certain groups 
of participants’ quality of life more than it does others’. However, since these 
analyses involve considerable exploratory modeling, results will be interpreted as 
hypothesis generating.  Relevant regression model assumptions will be evaluated 
using standard residual-based methods, and corrective measures such as 
normalizing transformations will be made as appropriate (75).  
 
We also will evaluate differences in quality of life using a more global approach 
developed by O’Brien (76) and proposed for use in quality of life studies by 
Tandon (77). In this analysis, the group differences in the individual quality of life 
dimensions will be combined using a weighted sum of the individual test 


Protocol ID97-077 
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statistics, with the weights chosen from the observed covariance matrix.  This 
summary statistic can then be used to test whether an overall difference exists 
between the two treatment groups with respect to the quality of life scales. 
 
We expect that the differences in quality of life at the follow-up periods will 
change over time.  Therefore, we will also attempt to formally characterize any 
pattern of change in quality of life using linear regression with a quadratic term in 
time. This will allow us to model reasonably smooth departures in time from 
strictly straight-line trends.  Interactions between the treatment group variable and 
time will indicate differing linear or quadratic trends in quality of life for the two 
treatment groups and will reveal whether the quality of life scores converge in 
time.  In order to preserve the overall type I error rate of 0.05, the interaction 
terms will also be tested at  = 0.01 for the individual quality of life scores.  Since 
a patient will contribute quality of life scores at several time points, the scores 
within each individual will be correlated. We will use the Generalized Estimating 
Equation (GEE) methodology to fit the regression models (78). GEE provides 
regression parameter estimates that have interpretations identical to those of 
standard linear regression methods.  The GEE models differ in that the standard 
error estimates of the regression coefficients are inflated to account for the 
observed correlation in the data.  One significant advantage of GEE is that data 
from all patients can be incorporated into the analyses.  For example, patients who 
contribute follow-up quality of life scores only at the 6 month follow-up can be 
included with those who contribute quality of life scores at each follow-up time.  
This maximizes the potential power available at the conclusion of the trial for 
evaluating the treatment-by-time interaction.  This approach to modeling patterns 
of change over time has been recently suggested for longitudinal quality of life 
data in a paper by Schumacher, Olschewski, and Schulger (79).  
 
Similar analyses will be conducted to evaluate quality of life among the spouses.  
 
13.2.2. Statistical Analysis of secondary quality of life hypotheses 
Analysis of utilities 
 
Hypothesis 2.1a: Utilities will change over time (insufficient data 
available to predict direction of change) 
.Hypothesis 2.1b: The severity/intensity o treatment-specific symptoms, 
weighted by the symptoms’ utilities, will be correlated with a rating of 
general health perceptions.  
Hypothesis 2.1c: Utilities assessed by telephone and in face-to-face 
interviews will not differ (UTMDACC patients only).  
Hypothesis 2.1d: Utilities assessed by the time trade-off method will be 
significantly correlated with those assessed by a visual analog scale. 
Hypothesis 2.1e: The utility of “current health” will be related to quality 
of life indicators. 
For Hypothesis 2.1a, we will use a similar approach to that described above to 
evaluate quality of life changes over time.  Specifically, we will first conduct 
descriptive analyses to characterize the distributions of patient preferences at the 
different time points for the two groups.  This will be followed by formally testing 


Protocol ID97-077 
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the differences in patient preferences between the two groups using t-tests.  
Regression analyses using the GEE methodology will be used to specifically 
model the changes in patient preferences over time. 
 
For Hypotheses 2.1b, 2.1d, and 2.1e we will use Pearson’s Product Moment 
correlation coefficients to evaluate the respective hypotheses.  We will use 
graphical methods including boxplots, histograms, and scatterplots to evaluate the 
distributional assumptions and use nonparametric rank correlations if necessary. 
 
Finally, in testing Hypothesis 2.1c we will use linear regression.  In this analysis, 
utilities will be regressed onto an indicator variable representing type of interview 
(telephone vs. face-to-face) together with potential confounders such as age and 
socioeconomic status.  Confounders will be included in the equation if they 
significantly (p < .05) improve the fit of the model.  Regression model 
assumptions will be evaluated as described above. 
 
Because the analysis of the secondary hypotheses are considered largely 
exploratory, no adjustments will be made for multiple comparisons.   
Mediation of treatment effect on quality of life 
Hypothesis 2.2: Treatment effects on quality of life will be mediated by 
treatment-specific symptoms and recurrence of disease. 
We hypothesize that the effect of treatment on quality of life will be mediated by 
recurrence and/or treatment-specific symptoms.  To evaluate whether these 
variables act as mediating variables between treatment and quality of life, we will 
use the criteria described by Baron and Kenny (80). Evidence of mediation for a 
particular variable would be indicated by (1) the treatment is related to the 
hypothesized mediating variable, (2) the mediating variable is related to quality of 
life, and (3) inclusion of the hypothesized mediating variable in the model reduces 
the direct effect of treatment on quality of life. The mediational hypothesis will be 
investigated for each of the quality of life indices.  Three regression equations will 
be estimated to assess whether all specified criteria are met.  For example, to test 
condition 1, the mediating variable will be regressed onto the treatment variable; 
we will assess whether differences in recurrence and treatment-specific symptoms 
results from differences in treatment group.  If significant treatment effects are 
found, then we will proceed to determine if criteria 2 and 3 are satisfied. 
 
We will use a structural equation modeling framework to evaluate the mediating 
effects of recurrence and treatment-specific symptoms individually and 
simultaneously.  The structural equation modeling approach allows one to control 
for measurement error in the mediating variables, control for baseline quality of 
life, fit the entire mediational process rather than individual components, and use 
multiple mediators and multiple outcomes.  The mediational hypothesis suggests 
that the indirect effect of the treatment variable on the quality of life indices 
through the mediators is statistically important, and inclusion of this indirect 
effect will reduce the direct effect of the treatment variable on quality of life.  
First, we will fit the model that accounts for the direct effects of the treatment 
variable to the mediator variables and quality of life measures. Then, the paths 
from the mediator variables to the quality of life measures will be included.  The 


Protocol ID97-077 
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change in chi-squared statistic will indicate whether the mediational paths are 
statistically important.  
Interactive dyadic effects on quality of life 
Hypothesis 2.3a: Changes in the patient’s quality of life will influence the 
spouse’s quality of life. 
Hypothesis 2.3b: Changes in the spouse’s quality of life will influence the 
patient’s quality of life. 
Hypothesis 2.3c: The influence of each partner’s quality of life on the quality 
of life of the other partner will be moderated by the couple’s marital distress. 
Sequential dyadic interaction models (68,81-82) will be used to evaluate the 
nature of the quality of life relational patterns between the patient and his wife.  
These models allow (a) measurements at multiple time points, (b) measurements 
of multiple quality of life variables, and (c) measurements of multiple attribute 
variables.  The models predict the joint probability of patient’s and spouse’s 
quality of life responses at the six-month follow-up visit to be a function of their 
quality of life at baseline, and the joint probability of their quality of life responses 
at the 12-month follow-up to be a function of their quality of life at baseline and 
the six-month follow-up.  The model will include parameters that reflect: 
 
(1) Self-influences: the quality of life of each dyad member predicts 
that  member's future quality of life. 
 
(2) Reciprocity: the tendency for consensus on quality of life by 
patient  and spouse at each time point. 
 
 
(3) Direct dominance: the quality of life of one member of the dyad 
(e.g., patient) predicts the future quality of life of the other member 
(e.g., spouse). 
 
 
(4) Indirect dominance: the quality of life of one member of the dyad 
(e.g., patient) predicts the future joint quality of life of the dyad 
pair. 
 
The analysis will be conducted for each individual quality of life index.  
Following the univariate analyses, multiple indices will be examined to 
investigate more complex hypotheses, such as: (1) patient symptomatology 
influences the spouse's quality of life; and (2) the psychological well-being and 
sexual functioning of patient and spouse predict marital distress.  Finally, the 
effect of treatment group on the level of reciprocity and dominance will be 
examined. 
 
 
14.0 
Data and Protocol Management  
 
 
Protocol Study Oversight 
 
The University of Texas M. D. Anderson Cancer Center (MDACC) Institutional 
Review Board (IRB) will provide oversight solely for study patients treated at 


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MDACC. Participating study sites that are part of the Linked Urology Research 
Network (LURN) will have study oversight provided by a central institutional 
review board. Other participating academic institutions (i.e., not MDACCC or 
LURN) should obtain IRB approval from their IRB who will oversee the study. 
 
All patients entered from MDACC and participating sites will be registered by the 
MDACC Data Management Center (DMC) at (713) 792-8519.  IRB approval will 
be verified and the eligibility checklist will be reviewed.  No patient can be 
entered on protocol if they do not satisfy all eligibility requirements.  Protocol 
specific forms will be utilized for data acquisition.  Data will be monitored by the 
principal investigator every 3 months. 
 
 
The MDACC Extramural Collaborators Procedures documents the data 
management and quality assurance programs for this collaboration. 
 
 
Principal Investigators:  The M.D. Anderson Principal Investigator will be 
responsible for the conduct of the study and monitoring its progress.  The 
responsibility for all reports and forms required will be that of the principal 
investigator. 
 
 
Procedures for Patient Entry:  All Extramural Collaborators patients will be 
registered by the Data Management Center of the Department of Biostatistics at 
(713) 792-8519, from 8:00 a.m. – 5:00 p.m.  (CST).  The eligibility checklist will 
be faxed before registering/randomizing a patient.  This office will then enter the 
patients on the Protocol Data Management Center (PDMS).  All eligibility 
requirements will be checked prior to registration.  No patient can be entered on 
protocol if they do not satisfy all eligibility requirements. 
 
Data Management:  All data will be entered in PDMS at MDACC.  Data from 
Extramural Collaborators will be forwarded by hard copy.  Protocol-specific 
forms are attached to this study for use by the Extramural Collaborators.  All 
investigators will utilize these forms for onstudy, flowsheet, offstudy and toxicity 
data. 
 
Data Monitoring: All CRF’s will be monitored and collected by the MDACC  
DMC. 
 
All submitted forms will be monitored by the MDACC research nurse specifically 
assigned to this protocol.  Any major deficiencies will be corrected by telephone 
communication.  All data forms will be monitored for completeness of data.  Key 
parameters such as drug dosages including attenuations and escalations, adverse 
event documentation, and tumor measurements will analyzed. 
 
The schedule for form submission is as follows: 
 
 
On study form, Informed consent, 
 
14 days after registration 
 
Pathology, Flowsheet (#1) 
 
 
 
Eligibility Checklist 
 
 
Flowsheet interim evaluations 
21 days after evaluation  


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Offstudy 
 14 days after offstudy date 
 
 
Reportable adverse drug reaction 
 7 days after occurrence 
 
 
Toxicity Surveillance:  All major (Grade 4 and 5) or unexpected toxicities will be 
reported within 24 hours to the Data Management Center at (713) 792-8519.  The 
principal investigator at MDACC will be responsible for communicating toxicity 
reactions..  All Extramural Collaborators reporting a major toxicity will submit a 
toxicity form within 7 days of the occurrence.  All Grade 2-3 unknown reactions 
will be reported in writing within 7 working days. 
 
 
The standard FDA Adverse Reaction Report (MedWatch) reporting form will be 
used for reporting toxicities and unknown reactions.  The guidelines for reporting 
adverse drug reactions to MedWatch are outlined in the section entitled Reporting 
Requirements. 
 
 
Quality Assurance: Quality assurance measures are provided by three 
mechanisms:  ongoing monitoring of protocol compliance, on-site audits and 
response reviews.  All data submitted to the Data Management Center will be 
monitored for timeliness of submission, completeness and adherence to protocol 
requirements.  Monitoring will begin at the time of patient registration and will 
continue during protocol performance and completion.  The MDACC Data 
Management Center research nurses will perform the on-going protocol 
compliance with the support of Extramural Data Management personnel. 
 
 
All records, x-rays, and scans will be sent to Houston for confirmation of 
progression. 
 
 
Drug Ordering: Drug to be supplied by AstraZeneca Pharmaceutical company to 
the M. D. Anderson Cancer Center Pharmacy for patients randomized to initial 
therapy (Arm A). Drug will be shipped from M. D. Anderson to Extramural 
Collaborators as necessary.  Each institution will maintain its own drug logs in 
accordance with MedWatch requirements. 
 
 
Institutional Review:  Each Extramural Collaborator will submit the protocol to 
their own Institutional Review Board.  Documentation of approval of the IRB will 
be forwarded to the MDACC Data Management Center - Box 501, 1515 
Holcombe Blvd., Houston, Texas 77030 before a patient from that institution can 
be registered on protocol.  No changes in the protocol will be allowed unless 
approved by the MDACC principal investigator.  All IRBs will have an OPRR 
Assurance number. 
 
 
Protocol Revisions and Closures: 
 
Non life-threatening revisions:  Extramural Collaborators will receive written 
notification of protocol revisions regarding non-life threatening events and will be 
given 7 days from receipt of the notification to implement the revision. 
 


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Life-threatening revisions: Extramural Collaborators will receive telephone 
notification of life-threatening revisions with follow up by mail.  Life-threatening 
protocol revisions will be implemented immediately. 
 
 
Protocol closures and temporary holds: Extramural Collaborators will receive 
telephone notification of protocol closures and temporary holds, with follow up by 
mail.  Closures and holds will be effective immediately. Extramural Collaborators 
will be updated on an ongoing basis about protocol accrual data so that they will 
be aware of imminent protocol closures. 
 
 
 
14.1  Reporting Requirements 
 
 
All patients will be monitored for adverse events occurring coincident to study 
drug administration. Adverse events will be recorded in the appropriate section of 
the case report form.  Reports will include the nature of the incident, its severity, 
relationship to drug, date, and time of onset, duration, outcome and specific or 
symptomatic therapy. Events clearly related to treatment or unexpected life 
threatening toxicities will be reported immediately to MDACC DMC who in turn 
will notify the study chairman and the Surveillance Committee.  
 
14.2  Quality of Life Data Management 
 
Data management for the quality of life companion study will be done by the data 
management and analysis core in the department of behavioral science.  Data 
collected by telephone interview will be entered directly into a computer using a 
Computer Assisted Telephone Interview (CATI) system.  Data collected using in-
person interviews will be entered using Access database software.  Participant 
names will not be included in the data file.  A participant’s record in the data file 
will be identified by a study identification number only, and the file linking study 
identification numbers and names will be kept in a separate location.  Only Dr. 
Basen-Engquist and the quality of life study coordinator will have access to this 
file. 
 
Weekly and monthly backups will be made of all quality of life study data.  The 
monthly back-up tapes will be stored in a fireproof safe. 
 
15.0  Adverse Events and Reporting Requirements (M. D. Anderson patients) 
 
 
All patients will be monitored for adverse events occurring coincident to study 
drug administration. Adverse events will be recorded in the appropriate section of 
the institutional case report form.  Reports will include the nature of the incident, 
its severity, relationship to drug, date, and time of onset, duration, outcome and 
specific or symptomatic therapy. Events clearly related to treatment or unexpected 
life threatening toxicities will be reported immediately to the study chairman who, 
in turn, must notify the Surveillance Committee. The MedWatch reporting form 
will be used for reporting toxicities and unknown reactions.  
 
 
 
Unknown Toxicities 
 
 
 


Protocol ID97-077 
Revised 07/26/06 
Page 24 
 
 
 
1. Grade 2 - 3 
 
 
1. A standard FDA Adverse Reaction Report (Form 3500, MedWatch for 
commercial drugs) within 7 working days to MDACC Data 
Management Center. 
 
 
 
 
 
b. MDACC Data Management Center will forward ADR form to OPR and  
 
 
primary investigator to meet 10 day reporting deadline. 
 
 
2.  Grade 4 and 5 
 
 
 
 
 
a. Telephone MDACC Data Management Center at (713) 792-8519   
 
 
within 24 hours to report toxicity. 
 
 
 
2. MDACC Data Management Center will telephone primary investigator 
immediately after receiving the Extramural Collaborator’s call to report 
toxicity.  
 
  
 
3. Submit a Standard FDA Adverse Reaction Report Form 3500, MedWatch 
for commercial drugs) within 7 working days to MDACC Data 
Management Center. 
 
 
 
 
4. MDACC Data Management Center will forward ADR form to OPR and 
 
principal investigator to meet 10 days reporting deadline. 
 
 


Protocol ID97-077 
Revised 07/26/06 
Page 25 
 
REFERENCES 
 
1. Gibbons, RP, Correa, RJ, Brannen, GE, Weissman, RM: Total prostatectomy for 
clinically localized prostatic cancer: long-term results. J.Urol., 141: 564-566, 
1989. 
 
2. Paulson, DF: Impact of radical prostatectomy in the management of clinically 
localized disease. J. Urol., 152: 1826-1830, 1994. 
 
3. Paulson, DF, Moul, JD, Walther, PJ: Radical prostatectomy for clinical stage T1-
T2NOMO prostatic adenocarcinoma: long-term results. J. Urol., 144: 1180-1184, 
1990. 
 
4. Oesterling, JE: Prostate specific antigen: a critical assessment of the most useful 
tumor marker for adenocarcinoma of the prostate. J. Urol., 145: 907-923, 1991. 
 
5. Partin, AW, Pearson, JD, Landis, PK, Carter, HB, Pound, CR, Clemens, JQ, 
Epstein, JI, Walsh, PC: Evaluation of prostate-specific antigen velocity after 
radical prostatectomy to distinguish local recurrence versus distant metastases. 
Urology, 43: 649-659, 1994. 
 
6. Stein, A, Dekernion, JB, Smith, RB, Dorey, F, Patel, H: Prostate specific antigen 
levels after radical prostatectomy in patients with organ confined and locally 
extensive prostate cancer. J.Urol., 147: 942-946, 1992. 
 
7. Partin, AW, Pound, CR, Clemens, JQ, Epstein JI, Walsh, PC: Serum PSA after 
anatomic radical prostatectomy: the Johns Hopkins experience after 10 years. 
Urol. Clin. N. Amer., 20(4): 713-725, 1993. 
 
8. Partin, AW, Lee, BR, Carmichael, M, Walsh, PC, Epstein, JI: Radical 
prostatectomy for high-grade disease: a re-evaluation 1994. J. Urol., 151: 1583-
1586, 1994. 
 
9. Ohori, M, Goad, JR, Wheeler, TM, Eastham, JA, Thompson TC, Scardino, PT: 
Can radical prostatectomy alter the progression of poorly differentiated prostate 
cancer? J. Urol., 152: 1843-1849,1994. 
 
10. Epstein, JI, Pizov, G, Walsh, PC: Correlation of pathologic findings with 
progression after radical retropubic prostatectomy. Cancer, 71(11): 3582-3593, 
1993. 
 
11. Zagars, GK, Pollack, A: Radiation therapy for T1 and T2 prostate cancer; 
prostate-specific antigen and disease outcome. Urol., 45(3): 476-483, 1994. 
 
12. Sgrignoli, AR, Walsh, PC, Steinberg, GD, Steiner, MS, Epstein, JI: Prognostic 
factors in men with stage D1 prostate cancer: identification of patients less likely 
to have prolonged survival after radical prostatectomy. J. Urol., 152: 1077-1081, 
1994. 
 


Protocol ID97-077 
Revised 07/26/06 
Page 26 
 
13. Zagars, GK, Sands, ME, Pollack, A, von Eschenbach, AC: Early androgen 
ablation for stage (N1 TO N3, MO) prostate cancer: prognostic variables and 
outcome. J. Urol., 151: 1330-1333, 1994.  
 
14. Sands, ME, Pollack, A, Zagars, GK: Influence of radiotherapy on node-positive 
prostate cancer treated with androgen ablation. Int. J. Radiat. Oncol. Biol. Phys., 
31: 13-18, 1995. 
 
15. Cheng, CWS, Bergstralh, EJ, Zincke, H: Stage D1 prostate cancer: a on 
randomized comparison of conservative treatment options versus radical 
prostatectomy. Cancer (supp) 71(3): 996-1004, 1993. 
 
16. Messing, EM, Manola, J, Sarosdy, M, Wilding, G, Crawford, ED, Trump, D,: 
Immediate Hormonal therapy compared with Observation After Radical 
Prostatectomy and Pelvic Lymphadenectomy In Men With Node-Positive Prostate 
Cancer. N Engl J Med 341: 1781-1788, 1999 
 
17. Han, M, Partin, AW, Pound, CR, Epstein, JI, Walsh, PC: Long Term 
Biochemical Disease-Free and Cancer Specific Survival Following Anatomic 
Radical Retropubic Prostatectomy. Urol Clin N Am 28: 555-565, 2001 
 
18. Lau, WK, Bergstralh, EJ, Blute, ML, Slezak, JM, Zincke, H: Radical 
Prostatectomy for Pathological Gleason 8 or Greater Prostate Cancer: Influence 
Of Concomitant  Pathological Variables. J Urol 167: 117-122, 2002 
 
19. Mian, BM, Troncoso, P, Okihara, K, Bhadkamkar, V, Johnston, D, Reyes, AO, 
Babaian, RJ: Outcome Of Patients With Gleason Score 8 or higher Prostate 
Cancer Following Radical Prostatectomy Alone. J Urol 167: 1675-1680, 2002 
 
20. Petrovich Z, Lieskovsky, G, Freeman, J, Luxton, G, Groshen, S, Formenti, S, 
Baert L, Chen S, Skinner, DG: Surgery with adjuvant irradiation in patients with 
pathologic stage C adenocarcinoma of the prostate. Cancer, 76(9): 1621-1628, 
1995. 
 
21. Zietman, AL, Coen, JJ, Shipley, WU, Althausen, AF: Adjuvant irradiation after 
radical prostatectomy for adenocarcinoma of prostate: analysis of freedom from 
PSA failure. Urol., 42(3): 292-299, 1993. 
 
22. Crawford, ED, Eisenberger, MA, McLeod, DG, Spaulding, JT, Benson, R, Dorr, 
FA, Blumenstein, BA, Davis, MA, Goodman, PJ: A controlled trial of leuprolide 
with and without flutamide in prostatic carcinoma. N. Engl. J. Med., 321: 419-
424, 1989. 
 
23. Denis, LJ, Carneiro, De, Mouro, JL, Bono, A, Sylvester, R, Whelan, P, Newling, 
D, Depauw, M: Goserelin acetate and flutamide versus bilateral orchiectomy: a 
phase three eortc trial (30853). Urology, 42(2): 119-129, 1993. 
 
 
24. Janknegt, RA, Abbou, CC, Bartoletti, R, Bernstein-Hahn, L, Bracken, B, Brisset, 
JM, Calais, DF, Chishold, G, Crawford, ED, Debruyne, FM, Dijjkman, GD, Frick, 
J, Goedhls, L, Knonagel, H, Venner, PM: Orchiectomy and nilutamide or placebo 


Protocol ID97-077 
Revised 07/26/06 
Page 27 
 
as treatment of metastatic prostatic cancer in a multinational double-blind 
randomized trial. J. Urol., 149: 77-83, 1993. 
 
25. Prostate Cancer Trialists  Collaborative Group: Maximum androgen blockade in 
advanced prostate cancer: An overview of the randomized trials. Lancet 355: 
1491-1498, 2000. 
 
26. Eisenberger, MA, Blumenstein, BA, Crawford, ED et al: Bilateral Orchiectomy 
with or without flutamide for metastatic prostate cancer (NCI INT-0105 
SWOG/ECOG). N Engl J Med 339: 1036-1042, 1998. 
 
 
27. Soloway, MS, Sharifi, R, Wajsman, Z, McLeod, D, Wood, DP, Puras-Baez, A: 
Randomized prospective study comparing radical prostatectomy alone versus 
radical prostatectomy preceded by androgen blockade in clinical stage B2 
(T2BNXMX) prostate cancer. J. Urol., 154: 424-428, 1995. 
 
28. Von Poppel, H, Ridder, DD, Elgama, AA, Van De Voorde, W, Werbrouck, P, 
Ackaert,  K, Oyen, R, Pittomvils, LB: Neoadjuvant hormonal therapy before 
radical prostatectomy decreases the number of positive surgical margins in stage 
T2 prostate cancer: interim results of a prospective randomized trial. J. Urol., 154: 
429-434, 1995.   
 
29. Fradet, Y: The role of neoadjuvant androgen deprivation prior to radical 
prostatectomy. Urol. Clin. N. Am., 23(4): 575-585, 1996. 
 
30. Soloway, MS, Pareek, K, Sharifi, R, Wajsman, Z, McLeod, D, Wood, DP, Puras-
Baez, A, and the Lupron Depot Neoadjuvant Prostate Cancer Study Group. 
Neoadjuvant Androgen Ablation Before Radical Prostatectomy in cT2bNxM0 
Prostate Cancer: 5 year Results. J Urol 167: 112-116, 2002 
 
31. Gleave, ME, Goldenberg, SL, Jones, EC, Bruchovsky, N, Sullivan, LD: 
biochemical and pathological effects of 8 months of neoadjuvant androgen 
withdrawal therapy before radical prostatectomy in patients with clinically 
confined prostate cancer. J. Urol., 155(1): 213-219, 1996. 
 
32. Gleave, ME, Goldenberg, SL, Chin, JL, Warner, J, Saad F, Klotz, LH, Jewett, M, 
Kassabian, V, Chetner, M, Dupont, C, Van Rensellaer, S and the Cnandian Uro-
Oncology Group. Randomized Comparative Study of 3 versus 8-month 
Neoadjuvant Hormonal Therapy Before Radical Prostatectomy: Biochemical and 
Pathological Effects. J Urol 166: 500-507, 2001 
 
33. Pilepich, MV, Caplan, R, Byhardt, RW, Lawton, CA, Gallagher, JB, Mesic, JB, 
Hanks, GE, Coughlin, CT, Porter, A, Shipley, WU, Grignon, D: Phase III trial of 
androgen suppression using Goserelin in unfavorable-prognosis carcinoma of the 
prostate treated with definitive radiotherapy: Report of Radiation Therapy prostate 
treated with definitive radiotherapy: Report of Radiation Therapy Oncology 
Group Protocol 85-31. J. Clin. Oncol., 15: 1013-1021, 1997. 
                                                          
 


Protocol ID97-077 
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Page 28 
 
 
34. Bolla, M, Gonzalez, D, Warde, P, Dubois, JB, Mirimanoff, R, Storme, G, 
Bernier, J, Kuten, A, Sternberg, C, Gil, T, Collette, L, Pierart: Improved Survival 
In Patients with Locally Advanced Prostate Cancer Treated with Radiotherapy and 
Goserelin. N Engl J Med. 
 
35. Lawton, CA, Winter, K, Murray, K, Machtay, M, Mesic, JB, Hanks, GE, 
Coughlin, CY, Pilepich, MV. Updated Results Of The Phase III Radiation 
Therapy Oncology Group Trial 85-31 evaluating the Potential Benefit Of 
Androgen Suppression Following Standard Radiation Therapy For Unfavorable 
Prognosis  Carcinoma of the Prostate Int J Radiation Oncology Biol. Phys. 49: 
937-946, 2001. 
 
36. Wirth, M, Tyrrell, C, Wallace, M, Delaere, KP,  Sanchez-Chapado, M, Ramon, J, 
Hetherington, J, Pina, F, Heynes, CF, Borchers, TM, Morris, T, Stone, 
A,:Bicalutamide (Casodex) 150mg As Immediate Therapy In Patients with 
Localized or Locallly advanced Prostate Cancer Significantly reduces the risk of 
disease Progression. Urology 58: 146-151, 2001 
 
37. McHorney, CA, Ware, JE, Raczek, AE: The MOS 36-item short form health 
survey (SF-36):  II. Psychometric and clinical tests of validity in measuring 
physical and mental health constructs.  Medical Care, 31: 247-263, 1993. 
 
38. McNair, DM, Lorr, M, Droppleman, LF: Profile of mood states. San Diego, CA: 
Educational and Industrial Testing Service, 1992. 
 
39. Litwin, MS, Hays RD, Fink, A, Ganz, PA, Leake, B., Leach, GE, Brook, RH: 
Quality-of-life outcomes in men treated for localized prostate cancer. JAMA, 273: 
129-135, 1995. 
 
40. Spanier GB: The Dyadic Adjustment Scale by Spanier.  Journal of Marriage and 
the Family, 38:15-28, 1976. 
 
41. Nayfield, SG, Ganz, PA, Moinpour, CM, Cella, DF, Hailey, BJ: Report from a 
National Cancer Institute (USA) workshop on quality of life assessment in cancer 
clinical trials. Quality of Life 1: 203-210, 1992. 
 
42. Beckham JC, Godding PR. Sexual dysfunction in cancer patients. Journal of 
Psychosocial Oncology. 8(1):1-16, 1990. 
 
43. Debruyne FMJ, Dijkman GA. Advances and trends in hormonal therapy for 
advanced prostate cancer. European Urology. 28:177-188, 1995. 
 
44. Schover LR. Sexual rehabilitation after treatment for prostate cancer. Cancer 
(supplement). 71(3):1024-1030, 1993. 
 
45. Herr, HW, Kornblith, AB, Orman, U: A comparison of the quality of life of 
patients with metastatic prostate cancer who received or did not receive hormonal 
therapy.  Cancer (supplement), 71: 1143-1150, 1995. 
 


Protocol ID97-077 
Revised 07/26/06 
Page 29 
 
46. Kornblith, AB, Herr, HW, Ofman, US, Sher, HI, Holland, JC: Quality of life of 
patients with prostate cancer and their spouses.  Cancer, 73: 2791-2802, 1994. 
 
47. Cassileth, BR, Soloway, MS, Vogelzang, NJ, et al.: Quality of life and 
psychosocial status in stage D prostate cancer. Quality of Life Research. 
1992;1:323-330.  
 
48. da Silva, FC, Fossa, SD, Aaronson, NK, et al.: The quality of life of patients with 
newly diagnosed M1 prostate cancer: experience with EORTC clinical trial 
30853. European Journal of Cancer. 1996;32A(1):72-77.  
 
49. Cantor, SB. Decision analysis:  theory and application to medicine. Primary 
Care. 1995;22:261-270. 
 
50. Weeks, J: Taking quality of life into account in health economic analyses.  
Journal of the National Cancer Institute Monographs, 20: 23-27, 1996. 
 
51. Krahn, MD, Mahoney, J, Eckman, MH, Trachtenberg, J, Pauker, SG, Detsky, AS: 
Screening for prostate cancer:  a decision analytic view. Journal of the American 
Medical Association. 272(10):773-780, 1994. 
 
52. Fleming C, Wasson JH, Albertsen PC, Barry MJ, Wennberg JE, for the Prostate 
Patient Outcomes Research Team. A decision analysis of alternative treatment 
strategies for clinically localized prostate cancer. Journal of the American Medical 
Association. 269(20):2650-2658, 1993. 
 
53. Volk RJ, Cantor SB, Spann SJ, Cass AR, Cardena MP, Warren MM. Preferences 
of husbands and wives for prostate cancer screening. Archives of Family 
Medicine. 6:72-76, 1993. 
 
54. Clipp EC, George LK. Demetia and cancer:  a comparison of spouse caregivers. 
The Gerontologist. 33:534-541, 1993. 
 
55. Zarit SH, Reever KE, Bach-Peterson J. Relatives of the impaired elderly:  
correlates of feelings of burden. The Gerontologist. 20:649-655, 1980. 
 
56. Kiecolt-Glaser JK, Glaser R, Shuttleworth E, Dyer CS, Ogrocki P, Speicher CE. 
Chronic stress and immunity in family caregivers of Alzheimer’s disease victims. 
Psychosomatic Medicine. 49:523-535, 1987. 
 
57. Zarit SH, Todd PA, Zaarit JM. Subjective burden of husbands and wives as 
caregivers: a longitudinal study. The Gerontologist. 26:260-266, 1986. 
 
58. Keitel MA, Zevon MA, Rounds JB, Petrelli NJ, Karakousis C. Spouse 
adjustment to cancer surgery: distress and coping responses. Journal of Surgical 
Oncology.;43:148-153, 1990. 
 
59. Northouse L. A longitudinal study of the adjustment of patients and husbands to 
breast cancer. Oncology Nursing Forum., 16:511-516, 1989. 
 


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Page 30 
 
60. Zahalis EH, Shands ME. The impact of breast cancer on the partner 18 months 
after diagnosis. Seminars in Oncology Nursing.; 9:83-87, 1993. 
 
61. Compas BE, Worsham NL, Epping-Jordan JE, et al. When mom or dad has 
cancer: markers of psychological distress in cancer patients, spouses, and children. 
Health Psychology; 13:507-515, 1994. 
 
62. Given CW, Stommel M, Given B, Osuch J, Kurtz ME, Kurtz JC. The influence 
of cancer patients’ symptoms and functional states on patients’ depression and 
family caregivers’ reaction and depression. Health Psychology. 1993;12:277-285. 
 
63. Lewis FM, Woods NF, Hough EE, Bensley LS. The family’s functioning with 
chronic illness in the mother: the spouse’s perspective. Social Science and 
Medicine. 1989;29:1261-1269. 
 
64. Schumacher KL, Dodd MJ, Paul SM. The stress process in family caregivers of 
persons receiving chemotherapy. Research in Nursing & Health; 16:395-404, 
1993. 
 
65. Ell KO, Nishimoto RH, Mantell JE, Hamovitch MB. Psychological adaptation to 
cancer:  a comparison among patients, spouses, and nonspouses. Family Systems 
Medicine.;6:335-348, 1988. 
 
66. Gritz ER, Wellisch DK, Siau J, Wang HJ.  Long-term effects of testicular cancer 
on marital relationships.  Psychosomatics.  31: 301-312, 1990. 
 
67. Budescu DV. Tests of lagged dominance in sequential dyadic interaction. 
Psychological Bulletin. 96:402-414, 1984. 
 
68. Iacobucci D, Wasserman S. A general framework for the statistical analysis of 
sequential dyadic interaction data. Psychological Bulletin., 103:379-390, 1988. 
 
69. Wasserman S, Iacobucci D. Statistical analysis of discrete relational data. British 
Journal of Mathematical and Statistical Psychology. ;39: 41-64, 1986. 
 
70. Thomas. Physicians’ Desk Reference, 57: 699-701, 2003. 
 
71. Schellhammer, P, Sharifi, R, Block, NL, Soloway, M, Venner, P, Patterson, AL, 
Sarosdy, M, Vogelsang, N, Jones, J, Kolvenberg, G: A controlled trial of 
bicalutamide versus flutamide each in combination with luteinizing-releasing 
hormone analogue therapy in patients with advanced prostate cancer. Urology, 
45(5): 745-752, 1995. 
 
72. Schellhammer, P, Sharifi, R, Block, NL, Soloway, M, Venner, P, Patterson, AL, 
Sarosdy, M, Vogelsang, N, Jones, J, Kolvenberg, G: Clinical Benefit Of 
Bicalutamide Compared with Flutamide In Combined Androgen Blockade for 
Patients with Advanced Prostatic Carcinoma: Final Report Of a Double-Blind 
Randomized , Multicenter Trial. Urology 50: 330-336, 1997. 
 


Protocol ID97-077 
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Page 31 
 
73. Wysowski, DK, Fourcroy, JL: Flutamide hepatotoxicity. J. Urol., 155: 209-212, 
1996. 
 
74. Cohen, J. Statistical power analysis for the behavioral sciences. Lawrence 
Erlbaum Associates, New Jersey, 1988. 
 
75. Neter J, Wasserman W, Kutner MH. Applied linear statistical models. Irwin, 
MA; 1990. 
 
76. O’Brien, PC: Procedures for comparing samples with multiple endpoints. 
Biometrics, 40: 1079-1087, 1984. 
 
77. Tandon, PK: Applications of global statistics in analyzing quality of life data. 
Statistics in Medicine, 9: 819-827, 1990. 
 
78. Liang KY, Zeger SL. Longitudinal data analysis using generalized linear models. 
Biometrika,. 73:13-22, 1986. 
 
79. Schumacher M, Olschewski M, Schulgen G. Assessment of quality of life in 
clinical trials. Statistics in Medicine,.1915-1930, 1991. 
 
80. Baron RM, Kenny DA. The moderator-mediator variable distinction in social 
psychological research: conceptual, strategic, and statistical considerations. 
Journal of Personality and Social Psychology. 51:1173-1182, 1986. 
 
81. Gottman JM. Time-series analysis of continuous data in dyads. In: Lamb ME, 
Suomi SJ, Stephenson GR, eds. Social interaction analysis:  Methodological 
issues. Madison: University of Wisconsin Press; :207-230, 1979. 
 
82. Klein CE, Prochazka A, Spitzer AL, Gordon B, Glode LM. Spousal report of 
quality of life in treatment for localized prostate cancer. Proceedings of the 
Annual Meeting of the American Society of Clinical Oncology. 15:A1630, 1996. 


 
 
 
Protocol ID97-077 
 
 
 
Revised 12-11-02  
 
 
 
Page 32 
 
 
 
 
 
Evaluation During Study-Flow Sheet 
 
 
Baseline 
1 
2 
3 
6 
9 
12 
18 
24 
25-60 
61-120 
 
within 90 days 
mos. 
mos. 
mos. 
mos. 
mos. 
mos. 
mos. 
mos. 
mos.(4) 
mos.(6) 
 
Complete History 
X 
 
Physical Exam 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
PSA 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
Liver Function Tests(1) 
 
X 
X 
X 
X 
X 
X 
X 
Prothrombin Time(2)  
X 
 
 
X 
X 
X 
X 
Bone Scan(3) 
 
X 
Pathology Consult 
 
X 
QOL 
 
X 
 
 
 
X 
 
X 
X 
X 
X(5) 
Adverse Events/Interim Progress 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
Research Blood 
X  
 
(1)Post randomization liver function tests only required on treatment arm 
Every 3 month follow up is (+/- 2 weeks) 
(2)Prothrombin time obtained every 3 months if on coumadin and receiving drug (Arm A) 
Every 6 month follow up is (+/- 1 month) 
(3)Required if PSA prior to surgery > 10 ng/ml 
Every 12 month follow up is (+/- 2 months) 
(4)Tests/visits every 6 months (+/- 1 months) 
(5)QOL every 12 months (+/- 2 months) 
(6)Tests/visits every 12 months (+/- 2 months) 
 


Protocol ID97-077 
Revised 10/21/03 
Page 35 
 
 
Dyadic Adjustment Scale 
 
 
 


Protocol ID97-077 
Revised 10/21/03 
Page 36 
 
 
DYADIC ADJUSTMENT SCALE 
 
Most persons have disagreements in their relationships.  Please indicate below the approximate extent of 
agreement or disagreement between you and your partner for each item on the following list. 
 
 
Always 
agree 
Almost 
always 
agree 
Occasionally 
disagree 
Frequently 
disagree 
Almost 
always 
disagree 
Always 
disagree 
1. Handling family finances. 
5 
4 
3 
2 
1 
0 
2. Matters of recreation. 
5 
4 
3 
2 
1 
0 
3. Religious matters. 
5 
4 
3 
2 
1 
0 
4. Demonstrations of affection. 
5 
4 
3 
2 
1 
0 
5. Friends. 
5 
4 
3 
2 
1 
0 
6. Sex relations. 
5 
4 
3 
2 
1 
0 
7. Conventionality (correct or proper behavior). 
5 
4 
3 
2 
1 
0 
8. Philosophy of life. 
5 
4 
3 
2 
1 
0 
9. Ways of dealing with parents or in-laws. 
5 
4 
3 
2 
1 
0 
10. Aims, goals, and things believed important. 
5 
4 
3 
2 
1 
0 
11. Amount of time spent together. 
5 
4 
3 
2 
1 
0 
12. Making major decisions. 
5 
4 
3 
2 
1 
0 
13. Household tasks. 
5 
4 
3 
2 
1 
0 
14. Leisure-time interests and activities. 
5 
4 
3 
2 
1 
0 
15. Career decisions. 
5 
4 
3 
2 
1 
0 
 
All of 
the time 
Most of 
the time 
More often 
than not 
Occasionally 
Rarely 
Never 
16. How often do you discuss or have you 
considered divorce, separation, or terminating 
your relationship? 
 
0 
 
1 
 
2 
 
3 
 
4 
 
5 
17. How often do you or your mate leave the 
house after a fight? 
 
0 
 
1 
 
2 
 
3 
 
4 
 
5 
18. In general, how often do you think that things 
between you and your partner are going well? 
 
0 
 
1 
 
2 
 
3 
 
4 
 
5 
19. Do you confide in your mate? 
0 
1 
2 
3 
4 
5 
20. Do you ever regret that you married (lived 
together)? 
 
0 
 
1 
 
2 
 
3 
 
4 
 
5 
21. How often do you and your partner quarrel? 
0 
1 
2 
3 
4 
5 
22. How often do you and your mate “get on each 
other’s nerves”? 
 
0 
 
1 
 
2 
 
3 
 
4 
 
5 
 


Protocol ID97-077 
Revised 10/21/03 
Page 37 
 
 
 
 
Every day 
Almost every 
day 
Occasionally 
Rarely 
Never 
23. Do you kiss your mate? 
4 
3 
2 
1 
0 
 
All of them 
Most of them 
Some of them 
Very few 
of them 
None of 
them 
24. Do you and your mate engage in outside 
interests together? 
4 
3 
2 
1 
0 
 
How often would you say the following occur between you and your mate: 
 
 
Never 
Less than 
once a 
month 
Once or 
twice a 
month 
Once or 
twice a 
week 
Once a 
day 
More 
often 
25. Have a stimulating exchange of ideas. 
0 
1 
2 
3 
4 
5 
26. Laugh together. 
0 
1 
2 
3 
4 
5 
27. Calmly discuss something. 
0 
1 
2 
3 
4 
5 
28. Work together on a project. 
0 
1 
2 
3 
4 
5 
 
These are some things about which couples sometimes agree and sometimes disagree.  Indicate if either 
item below caused differences of opinions or were problems in your relationship during the past few weeks. 
 
 
Yes 
No 
29. 
0 
1 
Being too tired for sex. 
30. 
0 
1 
Not showing love. 
 
31.  The following words represent different degrees of happiness in your relationship.  The word, “happy,” 
represents the degree of happiness of most relationships.  Please tell us which word best describes the 
degree of happiness, all things considered, in your relationship. 
 
0 
1 
2 
3 
4 
5 
6 
Extremely 
unhappy 
Fairly 
unhappy 
A little 
unhappy 
Happy 
Very happy 
Extremely 
happy 
Perfect 
 


Protocol ID97-077 
Revised 10/21/03 
Page 38 
 
 
32.  Which of the following statements best describes how you feel about the future of your relationship: 
 
5 
I want desperately for my relationship to succeed and would go to almost any lengths to see that it 
 
does. 
4 
I want very much for my relationship to succeed and will do all that I can to see that it does. 
3 
I want very much for my relationship to succeed and will do my fair share to see that it does. 
2  
It would be nice if my relationship succeeded, but I can’t do much more than I am doing now to 
 
help it succeed. 
1 
It would be nice if it succeeded, but I refuse to do any more than I am doing now to keep the 
 
relationship going. 
0 
My relationship can never succeed, and there is no more that I can do to keep the relationship 
 
going. 


Protocol ID97-077 
Revised 10/21/03 
Page 39 
 
 
 
 
 
 
 
 
Profile of Mood States (POMS) 


Protocol ID97-077 
Revised 10/21/03 
Page 40 
 
 
 
Below are words that describe feelings and moods people have.  Please read EVERY word carefully.  Then 
fill in ONE space under the answer which best describes how you feel RIGHT NOW (that is, at the present moment). 
 
Suppose the word is happy.  Mark the one answer which is closest to how you feel RIGHT NOW (that is, at 
the present moment). 
 
 
 
 
 
0 
= 
Much unlike this 
 
The numbers refer 
1 
= 
Slightly unlike this 
 
to these phrases.  
2 
= 
Slightly like this 
 
 
 
 
3 
= 
Much like this 
 
 
Much Unlike This 
Slightly Unlike This 
Slightly Like This 
Much Like This 
1. Composed..................... 
0 
1 
2 
3 
2. Angry............................ 
0 
1 
2 
3 
3. Cheerful........................ 
0 
1 
2 
3 
4. Weak............................. 
0 
1 
2 
3 
5. Tense............................ 
0 
1 
2 
3 
6. Confused....................... 
0 
1 
2 
3 
7. Lively............................ 
0 
1 
2 
3 
8. Sad................................ 
0 
1 
2 
3 
9. Friendly......................... 
0 
1 
2 
3 
10. Tired........................... 
0 
1 
2 
3 
11. Strong......................... 
0 
1 
2 
3 
12. Clearheaded................ 
0 
1 
2 
3 
13. Untroubled.................. 
0 
1 
2 
3 
14. Grouchy...................... 
0 
1 
2 
3 
15. Playful......................... 
0 
1 
2 
3 
16. Timid.......................... 
0 
1 
2 
3 
17. Nervous....................... 
0 
1 
2 
3 
18. Mixed-up..................... 
0 
1 
2 
3 
19. Vigorous..................... 
0 
1 
2 
3 
20. Dejected...................... 
0 
1 
2 
3 
21. Kindly......................... 
0 
1 
2 
3 
22. Fatigued...................... 
0 
1 
2 
3 
23. Bold............................ 
0 
1 
2 
3 
24. Efficient...................... 
0 
1 
2 
3 
25. Peaceful....................... 
0 
1 
2 
3 
26. Furious........................ 
0 
1 
2 
3 
27. Lighthearted................ 
0 
1 
2 
3 
 
Much Unlike This 
Slightly Unlike This 
Slightly Like This 
Much Like This 
28. Unsure......................... 
0 
1 
2 
3 


Protocol ID97-077 
Revised 10/21/03 
Page 41 
 
 
29. Jittery.......................... 
0 
1 
2 
3 
30. Bewildered.................. 
0 
1 
2 
3 
31. Energetic..................... 
0 
1 
2 
3 
32. Lonely......................... 
0 
1 
2 
3 
33. Sympathetic................. 
0 
1 
2 
3 
34. Exhausted.................... 
0 
1 
2 
3 
35. Powerful...................... 
0 
1 
2 
3 
36. Attentive..................... 
0 
1 
2 
3 
37. Serene......................... 
0 
1 
2 
3 
38. Bad tempered.............. 
0 
1 
2 
3 
39. Joyful.......................... 
0 
1 
2 
3 
40. Self-doubting............... 
0 
1 
2 
3 
41. Shaky.......................... 
0 
1 
2 
3 
42. Perplexed.................... 
0 
1 
2 
3 
43. Active.......................... 
0 
1 
2 
3 
44. Downhearted............... 
0 
1 
2 
3 
45. Agreeable.................... 
0 
1 
2 
3 
46. Sluggish...................... 
0 
1 
2 
3 
47. Forceful....................... 
0 
1 
2 
3 
48. Able to concentrate...... 
0 
1 
2 
3 
49. Calm........................... 
0 
1 
2 
3 
50. Mad............................ 
0 
1 
2 
3 
51. Jolly............................ 
0 
1 
2 
3 
52. Uncertain.................... 
0 
1 
2 
3 
53. Anxious....................... 
0 
1 
2 
3 
54. Muddled...................... 
0 
1 
2 
3 
55. Ready-to-go................. 
0 
1 
2 
3 
56. Discouraged................ 
0 
1 
2 
3 
57. Good-natured.............. 
0 
1 
2 
3 
58. Weary......................... 
0 
1 
2 
3 
59. Confident.................... 
0 
1 
2 
3 
60. Businesslike................ 
0 
1 
2 
3 
61. Relaxed....................... 
0 
1 
2 
3 
62. Annoyed...................... 
0 
1 
2 
3 
 
Much Unlike This 
Slightly Unlike This 
Slightly Like This 
Much Like This 
63. Elated.......................... 
0 
1 
2 
3 


Protocol ID97-077 
Revised 10/21/03 
Page 42 
 
 
64. Inadequate................... 
0 
1 
2 
3 
65. Uneasy........................ 
0 
1 
2 
3 
66. Dazed.......................... 
0 
1 
2 
3 
67. Full of pep................... 
0 
1 
2 
3 
68. Gloomy....................... 
0 
1 
2 
3 
69. Affectionate................. 
0 
1 
2 
3 
70. Drowsy........................ 
0 
1 
2 
3 
71. Self-assured................. 
0 
1 
2 
3 
72. Mentally alert.............. 
0 
1 
2 
3 
 


Protocol ID97-077 
Revised 10/21/03 
Page 43 
 
 
 
 
 
 
 
 
 
Medical Outcomes Study  
36-Item Short Form Health Survey (SF-
36) 


Protocol ID97-077 
Revised 10/21/03 
Page 44 
 
 
 
1. 
The following questions are about activities you might do during a typical day. 
 
Does your health now limit you in these activities?  If so, how much? 
 
(Circle 1, 2, or 3 on each line) 
 
Yes, 
Limited 
A Lot 
Yes, 
Limited 
A Little 
No, Not 
Limited 
At All 
a.  Vigorous activities, such as running, lifting heavy 
      objects, participating in strenuous sports.................... 
 
1 
 
2 
 
3 
 
 
 
 
b.  Moderate activities, such as moving a table, pushing a 
vacuum cleaner, bowling, or playing golf....... 
 
1 
 
2 
 
3 
 
 
 
 
c.  Lifting or carrying groceries........................................... 
1 
2 
3 
 
 
 
 
d.  Climbing several flights of stairs................................... 
1 
2 
3 
 
 
 
 
e.  Climbing one flight of stairs........................................... 
1 
2 
3 
 
 
 
 
f.  Bending, kneeling, or stooping....................................... 
1 
2 
3 
 
 
 
 
g.  Walking more than a mile.............................................. 
1 
2 
3 
 
 
 
 
h.  Walking several blocks................................................... 
1 
2 
3 
 
 
 
 
i..  Walking one block........................................................... 
1 
2 
3 
 
 
 
 
j.  Bathing or dressing yourself............................................ 
1 
2 
3 
 
2. 
During the PAST 4 WEEKS, have you had any of the following problems with your 
 
work or other regular daily activity as a resutl of your PHYSICAL HEALTH? 
 
(Please answer YES or NO for each question by circling 1 or 2 on each line.) 
 
Yes 
No 
 
a. Cut down the amount of time you spent on work or other activities                 
 
1 
 
2 
 
 
 
b.  Accomplished less than you would like                                                               
1 
2 
 
 
 
c.   Were limited in the kind of work or other activities                                           
1 
2 
 
 
 
d. Had difficulty performing the work or other activities (for example, it took 
    extra effort                                                                                                                
1 
2 
 


Protocol ID97-077 
Revised 10/21/03 
Page 45 
 
 
3. 
During the PAST 4 WEEKS, have you had any of the following problems with 
 
your work or other regular daily activities as a result of your EMOTIONAL  
PROBLEMS,  
such as feeling depressed or anxious? 
 
(Please answer YES or NO for each question by circling 1 or 2 on each line.) 
 
Yes 
 
No 
 
a. Cut down the amount of time you spent on work or other 
     activities                                                                                        
 
1 
 
2 
 
 
 
b.  Accomplished less than you would like                                   
1 
2 
 
 
 
c.  Didn’t do work or other activities as carefully as usual          
1 
2 
 
 
 
4. 
These questions are about how you feel and how things have been with you during the  PAST 
4 WEEKS.  For each questions, please give the one answer that comes closest to  
the way you 
have been feeling.   
 
How much of the time during the past 4 weeks... 
 
  (Circle one number on each line.) 
 
All  
of 
 the  
Time 
Most  
of  
the 
Time 
A Good 
Bit of  
the 
Time 
Some 
of  
the 
Time 
A 
Little 
of the 
Time 
None  
of  
the  
Time 
a.  Did you feel full of pep?                                
1 
2 
3 
4 
5 
6 
 
 
 
 
 
 
 
b.  Have you been a very nervous 
      person?                                                           
 
1 
 
2 
 
3 
 
4 
 
5 
 
6 
 
 
 
 
 
 
 
c.  Have you felt so down in the dumps     
     that nothing could cheer you up?                 
 
1 
 
2 
 
3 
 
4 
 
5 
 
6 
 
 
 
 
 
 
 
d.  Have you felt calm and peaceful?                
1 
2 
3 
4 
5 
6 
 
 
 
 
 
 
 
e.  Did you have a lot of energy?                       
1 
2 
3 
4 
5 
6 
 
 
 
 
 
 
 
f.  Have you felt downhearted and blue 
                                                                              
1 
2 
3 
4 
5 
6 
g.  Did you feel worn out?                                  
1 
2 
3 
4 
5 
6 
 
 
 
 
 
 
 
h.  Have you been a happy person?                  
1 
2 
3 
4 
5 
6 
 
 
 
 
 
 
 
i.  Did you feel tired?                                          
1 
2 
3 
4 
5 
6 
 
 
 


Protocol ID97-077 
Revised 10/21/03 
Page 46 
 
 
5.  During the past 4 weeks, how much of the time has your physical health or emotional problems  
interfered with your social activities (like visiting with friends, relatives, etc.)? 
 
 
 
 
All of the time ................................................................. 
 
1 
 
Most of the time............................................................... 
2 
 
Some of the time.............................................................. 
3 
(Circle one number) 
A little of the time............................................................ 
4 
 
None of the time.............................................................. 
5 
 
 
 
6.  During the past 4 weeks, to what extent has your physical health or emotional problems interfered  
     with your normal social activities with friends, friend, neighbors, or groups)? 
 
Not at all................................................................. 
 
1 
 
Slightly.................................................................. 
2 
 
Moderately............................................................. 
3 
(Circle one number) 
Quite a bit    .......................................................... 
4 
 
Extremely............................................................... 
5 
 
 
 
7.  How much bodily pain have you had during the past 4 weeks? 
 
None....................................................................... 
 
1 
 
Very mild........ ........................................................ 
2 
 
Mild........................................................................ 
3 
(Circle one number) 
Moderate.................................................................. 
4 
 
Severe..................................................................... 
5 
 
Very severe.............................................................. 
6 
 
 
 
8.  During the past 4 weeks, how much pain interfere with your normal work 
     (including both work outside the home and housework)? 
 
Not at all........................................................................... 
 
1 
 
Slightly.................................................................... 
2 
 
Moderately.... .......................................................... 
3 
(Circle one number) 
Quite a ................................................................... 
4 
 
Extremely................................................................ 
5 
 
 


Protocol ID97-077 
Revised 10/21/03 
Page 47 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
(Circle one number on each line.) 
 
 
 
 
 
Definitely 
True 
Mostly 
True 
Don’t 
Know 
Mostly 
False 
Definitely 
False 
a.  I seem to get sick a little easier 
1 
2 
3 
4 
5 
 
 
 
 
 
 
b.  I am as healthy as anyone I know 
1 
2 
3 
4 
5 
 
 
 
 
 
 
c.  I expect my health to get worse 
1 
2 
3 
4 
5 
 
 
 
 
 
 
d.  My health is excellent                       
1 
2 
3 
4 
5 
 
10.  In general, would you say your health is: 
 
Excellent.......................................... 
1 
 
 
 
 
Very Good.............................................. 
2 
 
 
 
 
Good............................................... 
3 
(Circle one number) 
 
 
 
Fair................................................. 
4 
 
 
 
 
Poor................................................ 
5 
 
 
11.  Compared to one year ago, how would you rate your health in general now? 
 
Much better now than one year ago.................... 
1 
 
 
 
 
Somewhat better now than one year ago.............. 
2 
 
 
 
 
About the me................................................ 
3 
(Circle one number) 
 
 
 
Somewhat worse now than one year ago.............. 
4 
 
 
 
 
Much worse now than one year ago................... 
5 
 
 
 
9.  Please choose the answer that best describes how true or false each of the 
     following statements is for you. 


Protocol ID97-077 
Revised 10/21/03 
Page 48 
 
 
 
 
 
 
 
 
Southwest Oncology Group Treatment 
Specific Symptom Scale 
 


Protocol ID97-077 
Revised 10/21/03 
Page 49 
 
 
 
TREATMENT-SPECIFIC SYMPTOMS 
 
The following items describe symptoms that are common for people undergoing treatment for prostate cancer.  
Please circle one number for each item and make your choice with respect to the last week. 
 
 
32. 
DIARRHEA 
 
 
 
1 
I seldom have more than two normal stools per day 
 
2 
I have occasional diarrhea (two or three loose stools per day, no more than  
 
once a 
week) 
 
3 
I have fairly frequent diarrhea (two or three loose stools per day several  
 
 
times a week) 
 
4 
I have frequent diarrhea (two or three loose or watery stools daily) 
 
5 
I have more than three watery stools daily 
 
6 
I have had a colostomy 
 
 
33. 
CRAMPY, ABDOMINAL PAIN 
 
 
1 
I seldom if ever have crampy, abdominal pain 
 
2 
I have occasional crampy, abdominal pain (no more than once a week) 
 
3 
I have fairly frequent crampy, abdominal pain (several times a week) 
 
4 
I have frequent crampy, abdominal pain (once a day) 
 
5 
I have crampy, abdominal pain several times a day 
 
 
34. 
TENDERNESS AND URGENCY WITH BOWEL MOVEMENTS 
 
1 
My bowel movements are normal 
 
2 
I have occasional mild urgency to move my bowels or tenderness with   
 
bowel 
movement (no more than once a week) 
 
3 
I have fairly frequent mild urgency or tenderness with my bowel  
 
 
 
movements (several times a week) 
 
4 
I have mild to moderate urgency, pain and occasional mild bleeding with  
 
 
bowel movements (no more than twice a week) 
 
5 
I have frequent severe urgency, pain or bleeding with bowel movements 
 
6 
I have had a colostomy 
 


Protocol ID97-077 
Revised 10/21/03 
Page 50 
 
 
 
35. 
URINE FLOW 
 
 
1 
My urine flows easily 
 
2 
My urine flows fairly easily 
 
3 
My urine flows slowly but I don’t have to strain or bear down to empty my bladder 
 
4 
My urine flows very slowly and I have to strain or bear down to empty my  
 
bladder 
 
5 
My urine flows very slowly and I have to strain or bear down a great deal  
 
 
to empty my bladder 
 
6 
I have an indwelling catheter 
 
 
36. 
In the past week did you: 
 
 
1 
Have total control over your urine flow 
 
2 
Have problems with dribbling, but not all the time or only at certain times  
 
 
of the day 
 
3 
Have a lot of problems with dribbling 
 
4 
Lose larger amounts of urine than dribbling but not all day long 
 
5 
Have no control over your urine flow (that is, you were totally incontinent) 
 
6 
I have an indwelling catheter 
 
 
37. 
In the past week, I tended to urinate 
 
 
1 
4 or less times a day 
 
2 
5 to 8 times a day 
 
3 
9 to 12 times a day 
 
4 
More than 12 times a day 
 
5 
I have an indwelling catheter 


Protocol ID97-077 
Revised 10/21/03 
Page 51 
 
 
 
 
 
38. 
GAS PAIN 
 
1. 
I seldom if ever feel bloated or have gas pain 
 
2. 
I have occasional gas pain (no more than once a week) 
 
3. 
I have fairly frequent gas pain (several times a week) 
 
4. 
I have frequent gas pain (once a day) 
 
5. 
I have gas pain several times a day 
 
 
39. 
HOT FLASHES 
 
1. 
I seldom if ever have hot flashes 
 
2. 
I have occasional hot flashes (several times a month) 
 
3. 
I have fairly frequent hot flashes (once a week) 
 
4. 
I have frequent hot flashes(several times a week) 
 
5. 
I have hot flashes several times a day 
 
 
40. 
BREAST TENDERNESS 
 
1. 
I do not have a problem with breast tenderness 
 
2. 
I have some breast tenderness but it doesn’t bother me 
 
3. 
I have breast tenderness that bothers me somewhat 
 
4. 
I have breast tenderness that bothers me a great deal 
 
5. 
My breast tenderness is unbearable 
 
 
41. 
BREAST SWELLING/ENLARGEMENT 
 
1. 
I do not have a problem with breast swelling 
 
2. 
I have some breast swelling but it doesn’t bother me 
 
3. 
I have breast swelling that bothers me somewhat 
 
4. 
I have breast swelling that bothers me a great deal 
 
5. 
My breast swelling is totally unacceptable to me 
 
 


Protocol ID97-077 
Revised 10/21/03 
Page 52 
 
 
 
 
 
 
 
 
UCLA Sexual Functioning Scale 


Protocol ID97-077 
Revised 10/21/03 
Page 53 
 
 
SEXUAL FUNCTION 
 
The next section is about your sexual function and sexual satisfaction.  many of the questions are very 
personal, but they will help us understand the important issues that you face every day.  Remember,  
YOUR NAME DOES NOT APPEAR ANYWHERE ON THIS SURVEY.  Please answer honestly about 
THE LAST 4 WEEKS ONLY. 
 
1.  How would you rate each of the following during the last 4 weeks? 
        (Circle Yes/No) 
 
 
 
Very  
Poor 
 
Poor 
 
Fair 
 
Good 
Very 
Good 
a.  Your level of sexual desire?................. 
1 
2 
3 
4 
5 
b. Your ability to have an erection?.............. 
1 
2 
3 
4 
5 
c. Your ability to reach orgasm (climax)?..... 
1 
2 
3 
4 
5 
 
2.  How would you describe the usual QUALITY of your erections? 
None at all............................................................... 
1 
 
Not firm enough for any sexual activity........................... 
2 
 
Firm enough for masturbation and foreplay only............................
3 
(Circle one number) 
Firm enough for intercourse......................................... 
4 
 
 
3.  How would you describe the FREQUENCY of your erections? 
I NEVER had an erection when I wanted one..................... 
1 
 
I had an erection LESS THAN HALF the time I wanted one.. 
2 
 
I had an erection ABOUT HALF the time I wanted 
one...................
3 
(Circle one number) 
I had an erection MORE THAN HALF the time I wanted one 
4 
 
I had an erection WHENEVER I wanted one..................... 
5 
 
 
4.  How often have you awakened in the morning or night with an erection? 
Never...................................................................... 
1 
 
Seldom (less than 25% of the time)................................. 
2 
 
Not often (less than half the time)................................... 
3 
(Circle one number 
Often (more than half the time)...................................... 
4 
 
Very often (more than 75% of the time)........................... 
5 
 


Protocol ID97-077 
Revised 10/21/03 
Page 54 
 
 
 
5.  During the last 4 weeks did you have vaginal or anal intercourse ? 
 No............................................................................ 
1 
 
 Yes, Once................................................................... 
2 
(Circle one number) 
 Yes, More than Once..................................................... 
3 
 
 
 
6.  Overall, how would you  rate your ability to function sexually during the last 4 weeks? 
 Very poor................................................................... 
1 
 
 Poor.......................................................................... 
2 
 
 Fair........................................................................... 
3 
(Circle one number) 
 Good......................................................................... 
4 
 
 Very good................................................................... 
5 
 
 
 
7.  Overall, how big a problem has your sexual function been for you during the last 4 weeks? 
 No problem.................................................................. 
1 
 
 Very small problem........................................................ 
2 
 
 Small problem.............................................................. 
3 
(Circle one number) 
 Moderate problem......................................................... 
4 
 
 Big problem................................................................. 
5 
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol ID97-077 
Revised 10/21/03 
Page 55 
 
 
Psychometric information on quality of life questionnaires 
 
The quality of life measures to be used are frequently used instruments whose reliability and validity have 
been tested.  Normative data are available for most of the measures, permitting comparisons of the scores obtained 
with samples of individuals from the general population.   
Medical Outcomes Study (SF-36) Health Survey  
The SF-36 is a measure of general quality of life. In a sample of patients with chronic medical and 
psychiatric conditions, internal consistency reliability coefficients were high for its eight scales: physical function 
(0.93), social function (0.85), bodily pain (0.82), emotional well-being (0.90), vitality (0.87), general health 
perceptions (0.78), role limitations due to physical problems (0.84), and role limitations due to emotional problems 
(0.83) (26). The SF-36 was designed for self, telephone, and interviewer administration.   
The SF-36 has been used in several studies of prostate cancer patients’ quality of life (28,79). In a sample of 
308 men receiving treatment for prostate cancer, internal consistency reliability coefficients for the eight scales were 
all greater than 0.80 (80).  
Profile of Mood States 
The Profile of Mood States (POMS) is included to provide a more comprehensive measure of emotional 
distress than the emotional well-being subscale of the SF-36.  The POMS includes 65 questions measuring six mood 
states: tension-anxiety, depression-dejection, anger-hostility, vigor-activity, fatigue-inertia, and confusion-
bewilderment. In a study of 350 male psychiatric outpatients, the internal consistency reliability for these states were: 
tension (0.92), depression (0.95), anger (0.92), vigor (0.89), fatigue (0.94), and confusion (0.87). In a sample of 650 
female psychiatric outpatients, the internal consistency reliabilities were: tension (0.90), depression (0.95), anger 
(0.93), vigor (0.87), fatigue (0.93), and confusion (0.84). Using this same data, a short version of the POMS was 
developed that consists of 30 items and the same six scales measured by the long form.  The internal consistency 
reliabilities for the short form ranged from 0.75 (confusion) to 0.90 (vigor) for females and 0.79 (confusion) to 0.91 
(fatigue) for males (27). The long form of the POMS has been used in studies evaluating the effects of treatment of 
prostate cancer (36,81) and to assess the emotional state of men with testicular cancer (82-84). In our pilot test, we 
will assess the reliability of the short form scales and the correlation of scores from the short and long versions of the 
POMS to determine if the short form is appropriate for our use. 
Southwest Oncology Group Treatment Specific Symptom Scale 
This scale was developed specifically to measure symptoms of patients receiving androgen ablation 
treatment for prostate cancer. It includes single items to measure diarrhea, abdominal pain, bowel function, gas pain, 
hot flashes, breast tenderness, and breast swelling; three items measure urine flow. Because items have not been 
summed to create an overall scale, but are scored separately, estimates of internal consistency reliability are not 
available (Carol Moinpour, Ph.D., personal communication, 1997).  This scale was used in a study to assess 
treatment-related symptoms after nerve-sparing radical prostatectomy for early (non-metastatic) prostate cancer (85). 
The scale also is being used in a SWOG study of intermittent androgen deprivation in patients with Stage D2 
prostate cancer.  In the SWOG study it is usually completed as a self-administered questionnaire, but it has been 
administered over the telephone for some participants. 
UCLA Sexual Functioning Scale 
We will assess sexual functioning using a scale developed at University of California – Los Angeles for a 
study of the quality of life of men treated for localized prostate cancer (28). In developing this scale, investigators 
held focus groups with 36 prostate cancer patients and their spouses to develop items related to sexual function and 
the degree of bother caused by problems.  After the items were developed their face validity was assessed by 
additional focus groups of patients and spouses and a panel of health care providers.  Items were then pretested in a 
mailed survey of 40 patients treated in Veterans Affairs hospitals for prostate cancer.  The data were factor analyzed 
and the scale was refined further.  The internal consistency and test-retest reliability of this scale are excellent (0.93 
and 0.92, respectively).  In interviews with the wives, this scale will be modified by eliminating the questions on 
erectile functioning. 


Protocol ID97-077 
Revised 10/21/03 
Page 56 
 
 
Dyadic Adjustment Scale (DAS) 
The DAS, a 32-item scale, measures four components of marital distress: satisfaction, cohesion, consensus, 
and expression of affection. Internal consistency reliability for the DAS is high (0.96). The scale has been tested 
extensively with both married and unmarried, cohabiting couples (29). The DAS has been used in several studies 
focusing on breast cancer patients and couples’ experiences with breast cancer (86,87). 
 
(References are provided in protocol reference list)  


Protocol ID97-077 
Revised 10/21/03 
Page 57 
 
 
 
 PATHOLOGY REVIEW FORM  
UT M.D.  Anderson Cancer Center 
 
 
Patient’s Name: 
 
Patient No.: 
 
No. of slides received: 
DOB: :         /        / 
No. of blocks received: 
Age: 
Designation block/s with tumor: 
Race: 
Designation block/s without tumor: 
Date Radical Prostatectomy:         /        / 
Block/s representative of tumor: Yes ____ No____ 
Date Slides Received:              /         / 
Block/s to request: 
Date Slides Returned:  
 /         / 
 
Hormonal ablation:  Yes 
No 
 
 
Gleason score: 
 
Gleason grades:         + 
 
 
 
 
Pelvic lymph nodes: 
 
Total 
 
 
Positive  
Negative 
 
Gleason score: 
Gleason grades: 
        + 
Carcinoma Organ confined: 
Yes 
 
No 
 
Extraprostatic extension: 
Yes 
 
No 
 
Margin of resection: 
Negative 
 
Positive  
Seminal vesicle involvement: 
Yes 
 
No 
 
 
Intraprostatic: 
 
Extraprostatic: 
 
Histologic type: 
Acinar  
 
Other: 
 
Notes: 
 
 
 
 
 
 
Reviewing Pathologist: 
 
 
Patricia Troncoso, M.D.  
 
 
    
 
                                            
 
 
Date 
 
Pre-treatment biopsy 
Radical prostatectomy 
Protocol ID 97-077