Radiation Therapy With or Without Antiandrogen Therapy in Treating Patients With Stage I or Stage II Prostate Cancer

OBJECTIVES: Primary: To evaluate whether a combination of Zoladex and flutamide used as cytoreductive agents prior to and during definitive radiation therapy improves overall survival over radiation therapy alone in locally confined carcinomas of the prostate; Secondary: To compare the rates of disease-specific survival, clinical relapse (local progression and/or distant failure), freedom from prostate-specific antigen (PSA) failure, freedom from second clinical relapse, freedom from second PSA relapse, and disease-free survival; To compare the prostate re-biopsy at two years; To measure the effect on sexual function.

OUTLINE: This is a randomized, multicenter study. Patients were stratified by PSA level (less than 4 vs 4-20), tumor differentiation (well vs moderate vs poor), nodal status (N0 [nodes evaluated by surgical sampling] vs NX [nodes evaluated negative by imaging methods only]), and participating center. Patients are randomized to one of two treatment arms. Arm I: Patients receive oral flutamide 3 times a day and goserelin subcutaneously once every 4 weeks, or once as a time release injection (intramuscular leuprolide may be substituted for goserelin), beginning 2 months prior to radiotherapy and continuing until completion of radiotherapy. Patients undergo radiotherapy daily 4-5 days per week for almost 8 weeks. Arm II: Patients undergo radiotherapy only, as in arm I. Patients are followed every 3 months for the remainder of the first year, every 4 months for the second year, every 6 months for the third through fifth years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 1980 patients within 5 years.

Inclusion criteria

• Histologically confirmed locally confined adenocarcinoma of the prostate with primary tumors confined to the prostate, clinical stage T1b,1c, 2a or 2b.
• Negative nodes evaluated by imaging methods (classified in the study as NX) or by surgical sampling (classified in the study as N0).
• Karnofsky performance status ≥ 70.
• PSA is mandatory, must be ≤ 20)
• No prior hormonal therapy, radiation or chemotherapy.
• Prior finasteride for prostate hypertrophy allowed if discontinued at least 60 days prior to randomization.
• Prior testosterone administration allowed if at least 90 days elapsed since last administration.
• No evidence of distant metastasis or other synchronous primary. Patients with prior invasive malignancy who were disease free for at least 5 years could be eligible with pre-randomization approval by the study chairman.
• Treatment begins within 21 days after randomization.
• Patients signs a study-specific informed consent form.
• Alanine Aminotransferase (ALT) within 2x upper normal limits.

Exclusion criteria

• Stage T1a or ≥ T2c disease.
• Lymph node involvement (N1 - N3).
• Evidence of distant metastasis. (M1)
• PSA > 20.
• Radical surgery or cryosurgery for carcinoma of the prostate, previous irradiation, antiandrogen therapy or chemotherapy.
• Previous or concurrent cancers other than basal cell or squamous cell skin carcinoma.

Patients with squamous cell carcinomas required to be NED (no evidence of disease) for a minimum of two years prior to study entry.

• Major medical or psychiatric illness which, in the investigator's opinion, would prevent completion of treatment and would interfere with follow-up.
• Karnofsky performance status of < 70.