Hyprofractionated Versus Conventionally Fractionated Radiation Therapy for Patients with Intermediate- or High-Risk, Localized, Prostate Cancer: 7-Year Outcomes From the Randomized, Multicenter, Open-Label, Phase 3 HYPRO Trial

Purpose: In the multicenter, phase 3, HYpofractionated irradiation for PROstate cancer trial, hypofractionated (HF) radiation therapy was compared with conventionally fractionated (CF) radiation therapy. In previous reports, we could not demonstrate the postulated superiority of hypofractionation in terms of relapse-free survival at 5 years. The frequent use of long-term androgen deprivation therapy might have had substantial effects on relapse-free survival. In the current analysis, we provide updated 7-year relapse-free survival outcomes. Methods and Materials: We enrolled patients with intermediate- to high-risk T1b-T4NX-N0MX-M0 localized prostate cancer. Patients were randomly assigned (1:1) to either HF (64.6 Gy in 19 fractions) or CF (78.0 Gy in 39 fractions) radiation therapy. Based on an estimated alpha/beta ratio for prostate cancer of 1.5 Gy, the EQD2 was 90.4 Gy for HF versus 78.0 Gy for CF radiation therapy. The primary endpoint of the present analysis is relapse-free survival at 7 years. Results: A total of 820 patients were enrolled, of whom 804 were assessable for the current evaluation (407 HF versus 397 CF). Median follow-up was 89 months (interquartile range, 83-99). Concomitant androgen deprivation therapy was prescribed for 537 ( 67%) of 804 patients for a median duration of 32 months (interquartile range, 10-44). Treatment failure at 7 years was reported in 220 (27.4%) of 804 patients, 107 ( 26.3%) in HF versus 113 (28.5%) in CF radiation therapy. Seven-year relapse-free survival was 71.7% (95% confidence interval [CI], 66.4-76.4) for HF versus 67.6% ( 95% CI, 62.0-72.5) for CF (P = .52). Overall survival was 80.8% (95% CI, 76.5-84.4) in HF versus 77.6% (95% CI, 73.0-81.5) in CF radiation therapy (P = .17). Conclusions: The current results of 7-year relapse-free survival confirmed our previous findings that the hypothesized dose escalation in the HF arm did not translate to superior tumor control compared with the CF arm. (C) 2019 Elsevier Inc. All rights reserved.