Trial Information

Phase III Randomized Trial Comparing Total Androgen Blockade Versus Total Androgen Blockade Plus Pelvic Irradiation in Clinical Stage T3-4, N0, M0 Adenocarcinoma of the Prostate

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.