Duration of androgen deprivation therapy in high-risk prostate cancer: A randomized trial.

Abstract

LBA4510 Background: Radiotherapy (RT) and long-term androgen deprivation therapy (ADT) is a standard treatment for patients with high-risk prostate cancer. However, the optimal duration of ADT is not yet defined. The purpose of this randomized trial was to compare outcomes between 36 and 18 months of ADT in high-risk prostate cancer treated with RT (PCS IV trial). Methods: PCS IV randomized patients with node-negative high-risk prostate cancer (T3-4, PSA >20 ng/ml or Gleason score >7), to pelvic RT (whole pelvis 44 Gy/4 ½ weeks, prostate 70 Gy/7 weeks) and 36 (arm 1) vs 18 months (arm 2) of ADT (neo- adjuvant, concomitant, adjuvant). ADT consisted of bicalutamide 50 mg for one month and goserelin 10.8 mg every three months for 36 vs 18 months. Overall survival was the primary end point. From randomization, overall and cancer-specific survival rates were compared between arms with Kaplan-Meier log rank test and Cox regression. Results: From October 2000 to January 2008, 310 patients were randomized to arm 1 and 320 to arm 2. Patients' characteristics were well balanced between the two arms (median age 71 years, median PSA 16 ng/ml, median Gleason score 8). Most patients had T2-T3 disease. At a median follow-up of 78 months, 80/310 patients (25.8%) in arm 1 and 85/320 (26.6%) in arm 2 had died (p=0.829). 113 patients died of causes other than prostate cancer. Overall and cancer-specific survival hazard ratios were 1.15 (0.85-1.56), p=0.366 and 1.07 (0.62-1.84), p=0.819, respectively. 5-year overall and disease-specific survival rates were 91.1% (87.9-94.3) vs. 86.1% (82.3-90.0), p=0.06 and 96.6% (94.5-98.7) vs. 95.3% (92.8-97.7), p=0.427 and 10-year overall and disease-specific survival rates were 61.9% (54.1-69.7) vs. 58.6% (49.8-67.4), p=0.275 and 84.1% (77.6-90.6) vs. 83.7% (76.3-91.1), p=0.819 for arm 1 and arm 2, respectively. There were no significant differences in the rates of biochemical, regional, or distant failure between arms. Conclusions: With a median follow-up of 6.5 years, our study shows that long-term ADT can be safely reduced from 36 to 18 months without compromising outcomes. Analysis of treatment impact on quality of life is now under review. Source of Funding: AstraZeneca Pharmaceuticals Grant. Clinical trial information: #NCT00223171.