Hormone Therapy With or Without Surgery or Radiation Therapy in Treating Patients With Prostate Cancer
Hormone Therapy With or Without Surgery or Radiation Therapy in Treating Patients With Prostate Cancer
RATIONALE: Hormones can stimulate the growth of prostate cancer cells. Hormone therapy may
 fight prostate cancer by reducing the production of androgens. Radiation therapy uses
 high-energy x-rays to damage tumor cells. It is not yet known whether hormone therapy plus
 surgery is more effective than hormone therapy plus radiation therapy for prostate cancer.

 PURPOSE: This randomized phase III trial is studying giving hormone therapy alone to see how
 well it works compared to giving hormone therapy together with bilateral orchiectomy or
 radiation therapy in treating patients with stage III or stage IV prostate cancer.
OBJECTIVES:

 -  Compare the overall survival, disease specific survival, and time to progression in
 patients with locally advanced adenocarcinoma of the prostate treated with total
 androgen suppression with or without pelvic irradiation.

 -  Compare the symptomatic control as measured by the rates of surgical interventions
 needed for control of local disease (e.g., transurethral resections, stent insertions,
 nephrostomies, and colostomies) in patients treated with these regimens.

 -  Compare the quality of life of patients treated with these regimens.

 -  Compare the sensitivity of the EORTC-QLQ-C30+3 and a trial-specific checklist (PR17)
 with the FACT-P questionnaire in measuring changes in quality of life of patients
 treated with these regimens.

 OUTLINE: This a randomized, multicenter study. Patients are stratified according to center,
 initial PSA level (less than 20 vs 20-50 vs greater than 50 ng/mL), method of node staging
 (clinical [no CT scan] vs radiological [CT scan negative] vs surgical), Gleason score (less
 than 8 vs 8-10), prior hormonal therapy (excluding orchiectomy) (yes vs no), and choice of
 hormonal therapy (bilateral orchiectomy with or without antiandrogen vs luteinizing
 hormone-releasing hormone [LHRH] with antiandrogen). Patients are randomized to 1 of 2
 treatment arms.

 -  Arm I: Patients receive antiandrogen therapy comprising oral flutamide every 8 hours,
 oral nilutamide every 8 hours for 1 month and then once daily, or oral bicalutamide once
 daily. Patients also choose to undergo bilateral orchiectomy or LHRH agonist therapy
 comprising goserelin subcutaneously (SC) every 4 weeks (short-acting formulation) or
 every 3 months (long-acting formulation), leuprolide intramuscularly every 4 weeks
 (short-acting formulation) or every 3 months (long-acting formulation), or buserelin SC
 every 8 weeks or every 12 weeks. Patients choosing orchiectomy may receive an
 antiandrogen for at least 6 weeks before surgery to counter any flare phenomenon and may
 continue the antiandrogen after surgery (at the physician's discretion).

 -  Arm II: Patients undergo total androgen ablation as in arm I. Patients with
 node-negative dissection undergo radiotherapy 5 days a week for 6.5-7 weeks. All other
 patients undergo radiotherapy 5 days a week for 5 weeks, followed by boost radiotherapy
 5 days a week for 2-2.4 weeks.

 Hormonal therapy on both arms continues in the absence of disease progression or unacceptable
 toxicity.

 Quality of life is assessed at baseline, on the last day of radiotherapy, at 6 months, and
 then every 6 months thereafter.

 Patients are followed at 1, 2, and 6 months and then every 6 months thereafter.

 PROJECTED ACCRUAL: A total of 1,200 patients will be accrued for this study within 7.5 years.
DISEASE CHARACTERISTICS:

 -  Histologically proven locally advanced adenocarcinoma of the prostate, defined as 1 of
 the following:

 -  T3-4, N0 or NX, M0

 -  T2, PSA greater than 40 µg/L

 -  T2, PSA greater than 20 µg/L AND Gleason score at least 8

 -  Diagnosis made within the past 6 months

 -  Gleason score and PSA known

 -  Pelvic lymph nodes must be clinically negative

 -  Lymph nodes no more than 1.5 cm in greatest diameter by CT scan or MRI of the
 pelvis

 -  Negative needle aspirate required for any lymph node more than 1.5 cm

 -  If a lymph node dissection was performed, it must be histologically negative

 -  No small cell or transitional cell carcinoma by biopsy

 -  No bony metastases by bone scan

 PATIENT CHARACTERISTICS:

 Age:

 -  Under 80

 Performance status:

 -  ECOG 0-2

 Life expectancy:

 -  At least 5 years excluding malignancy

 Hematopoietic:

 -  Hemoglobin at least 10.0 g/dL

 -  WBC at least 2,000/mm^3

 -  Platelet count at least 100,000/mm^3

 Hepatic:

 -  Bilirubin less than 2 times upper limit of normal (ULN)

 -  SGOT and SGPT less than 2 times ULN

 -  Alkaline phosphatase less than 2 times ULN

 -  No history of chronic liver disease

 Renal:

 -  Creatinine less than 2 times ULN

 Other:

 -  No contraindication to wide-field pelvic irradiation (e.g., inflammatory bowel disease
 or severe bladder irritability)

 -  No other malignancy within the past 5 years except nonmelanoma skin cancer

 -  Fertile patients must use effective contraception

 PRIOR CONCURRENT THERAPY:

 Biologic therapy:

 -  Not specified

 Chemotherapy:

 -  Not specified

 Endocrine therapy:

 -  Prior hormonal therapy within the past 12 weeks allowed provided the following
 conditions are met:

 -  Negative bone scan before beginning any hormonal therapy

 -  Extracapsular extension remains palpable on rectal re-exam

 -  Baseline PSA known before beginning any hormonal therapy

 -  At least 4-6 weeks since prior 5-alpha-reductase inhibitor (e.g., finasteride) for
 benign prostatic hypertrophy

 Radiotherapy:

 -  No prior pelvic irradiation

 Surgery:

 -  No prior radical prostatectomy

 -  Prior transurethral resection of the prostate allowed

 Other:

 -  No prior cytotoxic anticancer therapy

 -  No other prior treatment for prostate cancer

 -  No other concurrent anticancer therapy unless documented disease progression