Objective. To compare the outcomes of 18 months versus 36 months of androgen deprivation therapy (ADT) combined with radiation in high-risk prostate cancer (HRPC).
Design. Phase 3 multicenter, randomized superiority trial.
Participants. This study enrolled patients aged ≤ 80 years with HRPC. All patients had no evidence of regional or distant metastasis. High-risk disease was defined as any of the following: clinical stage T3 or T4, prostate-specific antigen (PSA) level > 20 ng/mL, or Gleason score > 7.
Methods. Prior to randomization, all patients received 4 months of ADT with goserelin 10.8 mg and anti-androgen therapy with bicalutamide 50 mg daily for 30 days. Patients were then randomly assigned to 18 (short arm) or 36 (long arm) months of ADT in combination with radiation therapy (RT). The randomization was stratified by stage (T1-2 vs T3-4), Gleason score (< 7 vs > 7) and PSA level (< 20 ng/mL vs > 20 ng/mL). The standard radiation dose was 70 Gy to the prostate and 44 Gy to the pelvis. Computed tomography or magnetic resonance imaging exam of the abdomen and pelvis and a bone scan were performed to rule out regional or distant metastases. PSA level was monitored every 3 months for 18 months, every 6 months up to the third year, and yearly thereafter.
Main outcome measures. The 2 primary outcomes were overall survival (OS) and quality of life (QoL) at 5 years. The secondary end points were biochemical failure (BF)defined as PSA nadir plus 2, disease-free survival (DFS), and site(s) of tumor relapse.
Main results. The 5-year OS was 91% and 86% for the 36- and 18-month groups, respectively (P = 0.07). The 10-year OS was 62% for both groups (P = 0.7), and the global hazard ratio (HR) was 1.02 (P = 0.8). The disease-specific survival (DSS) was similar in both groups at 5 years (98% vs 97%) and at 10 years (91% vs 92%) in the long versus short arm, respectively. The rate of prostate cancer–specific death was 21% versus 23% in the long versus short arm, respectively. In a multivariate analysis for OS, only age and Gleason score > 7 were statistically significant survival predictors. BF rate at 10 years was 25% for 36 months as compared with 31% for 18 months (HR, 0.71, P = 0.02). The 10-year DFS rates were 45% and 39% for 36 and 18 months, respectively (HR, 0.68, P = 0.08). Forty patients in the long arm versus 43 in the short arm developed distant metastasis. Both groups developed similar sites of metastasis, which was predominantly osseous. Some aspects of the EORTC30 and PR25 scales were significant, mostly pertaining to sexual activity, fatigue, and hormone-related symptoms in favor of the 18-month group. The median time to testosterone recovery after completion of ADT was 2.1 years for the short arm versus 4 years in the long arm (P = 0.02). The compliance rate with ADT was 88% in the short arm versus 53% in the long arm. The main reason for nonadherence was side effects in 54% of the patients in the long arm and 31% in the short arm.
Conclusion. The results of the current study suggest that 18 months of ADT in combination with RT yields similar 10-year OS and improved QoL compared with 36 months in patients with HRPC.