Phase III Radiation Therapy Oncology Group (RTOG) trial 86-10 of androgen deprivation adjuvant to definitive radiotherapy in locally advanced carcinoma of the prostate

Purpose: To test the hypothesis that androgen ablation before and during ra diotherapy for locally advanced carcinoma of the prostate may, by reducing tumor bulk and enhancing tumor cell kill, improve locoregional control and ultimately survival. Methods and Materials: The study was conducted from 1987 to 1991. Eligible patients were those with bulky tumors (T2-T4) with or without pelvic lymph node involvement and without evidence of distant metastases. They were rand omized to receive goserelin, 3.6 mg every 4 weeks; and flutamide, 250 mg t. i.d. for 2 months before radiation therapy and during radiation therapy (Ar m I), or radiation therapy alone (Arm II). Of 471 randomized patients, 456 were evaluable: 226 on Arm I and 230 on Arm II. Results: As of November 1999, the median follow-up has reached 6.7 years fo r all patients and 8.6 years for alive patients. At 8 years, androgen ablat ion has been associated with an improvement in local control (42% vs. 30%, p = 0.016), reduction in the incidence of distant metastases (34% vs. 45%, p = 0.04), disease-free survival (33% vs. 21%,p = 0.004), biochemical disea se-free survival = PSA <1.5 (24% vs. 10%, p < 0.0001), and cause-specific m ortality (23% vs. 31%, p = 0.05). however, subset analysis indicates that t he beneficial effect of short-term androgen ablation appears preferentially in patients with Gleason score 2-6. In that population, there is a highly significant improvement in all endpoints, including survival (70% vs. 52%,p = 0.015). In patients with Gleason 7-10 tumors, the regimen has not result ed in a significant enhancement in either locoregional control or survival. Conclusion: In patients with Gleason score 2-6 carcinoma of the prostate, a short course of androgen ablation as administered before and during radiot herapy has been associated with a highly significant improvement in local c ontrol, reduction in disease progression, and overall survival. (C) 2001 El sevier Science Inc.