Long-Term Follow-Up Analysis of NRG Oncology RTOG 0415: A Randomized Phase III Non-Inferiority Study Comparing Two Fractionation Schedules in Patients with Favorable-Risk Prostate Cancer

Purpose/Objective(s) To assess whether the efficacy of a hypofractionated (H) schedule is no worse than a conventional (C) schedule in men with low-risk prostate cancer. Materials/Methods Accrual began April 2006 and ended in December 2009. 1115 men with favorable-risk prostate cancer were randomly assigned 1:1 to a conventional (C) schedule (73.8 Gy in 41 fractions over 8.2 weeks) or to a hypofractionated (H) schedule (70 Gy in 28 fractions over 5.6 weeks). The trial was designed to establish with 90% power and alpha = 0.05 that (H) results in 5-year disease-free survival (DFS) that is not lower than (C) by more than 7% (hazard ratio (HR) < 1.52). Protocol specified secondary endpoints evaluated for noninferiority include: biochemical recurrence (BR), local progression, disease-specific survival, and overall survival. Results One thousand ninety-two protocol eligible men were analyzed: 542 to C and 550 to H. Median follow-up is 12.75 years. Baseline characteristics were not different according to treatment arm. The estimated 12-year DFS is 56.1% (95% CI 51.5, 60.5) in the C arm and 61.8% (57.2, 66.0) in the H arm. The DFS hazard ratio (H/C) is 0.85 (0.71-1.03), confirming non-inferiority (p<0.001). Twelve-year cumulative incidence of biochemical recurrence (BR) was 17.0% (CI 13.8, 20.5) in the C-RT and 9.9% (CI 7.5, 12.6) in the H-RT arm; (HR = 0.56, (0.40-0.78) suggesting improved efficacy with H. Additional pre-specified secondary endpoints were non-inferior Late Grade ≥ 3 GI toxicity is 3.2% (C) vs. 4.4% (H), Relative risk (RR) for H vs. C 1.39 (CI 0.75, 2.55) Late Grade ≥ 3 GU toxicity is 3.4% (C) vs. 4.2% (H), RR = 1.26 (CI 0.69, 2.30). Conclusion In men with favorable-risk prostate cancer, long-term disease-free survival is non-inferior with 70 Gy in 28 fractions compared to 73.8 Gy in 41 fractions. The risk of BR is reduced with moderate hypofractionation. No differences in late Grade ≥3 GI/GU toxicity were observed between the arms. (ClinicalTrials.gov identifier: NCT00331773)