Hypofractionated radiotherapy for prostate cancer (HYDRA): An individual patient data meta-analysis of randomized trials in the MARCAP consortium.

385 Background: Trials comparing moderately hypofractionated radiotherapy (MHFRT) against conventionally-fractionated radiotherapy (CFRT) for prostate cancer have varied considerably in intent (non-inferiority vs. superiority) and MHFRT dose. Herein, we compare the efficacy and toxicity profiles of isodose MHFRT and dose-escalated MHFRT. Methods: Individual patient data were obtained from 7 phase III trials comparing MHFRT vs. CFRT: three (n=3454) with isodose and four (n=2426) with dose-escalated MHFRT. Meta-analyses were designed to compare progression-free survival (PFS), late grade ≥2 genitourinary (GU) and late grade ≥2 gastrointestinal (GI) physician-scored toxicity, and clinically-significant decrements in patient-reported urinary or bowel quality of life (QOL). Results: After a median follow-up of 5.4 years (interquartile range [IQR], 4.6-7.2) and 7.1 years (IQR 5.7-8.4) following isodose and dose-escalated MHFRT, there were no differences in PFS (hazard ratio [HR] 0.92, 95%CI 0.81-1.05 and HR 0.94, 95%CI 0.82-1.09, respectively). Neither isodose nor dose-escalated MHFRT were associated with increased odds of grade ≥2 GU toxicity (odds ratio [OR] 1.16 95CI% 0.86-1.57 and OR 1.20, 95%CI 0.95-1.51). The odds of grade ≥2 GI toxicity were higher with dose-escalated (OR 1.48, 95%CI 1.14-1.92) but not isodose MHFRT (OR 1.30, 95% 0.59-2.87). Isodose MHFRT did not show different odds of urinary (OR 1.03, 95%CI 0.51-2.09) and bowel (OR 0.76, 95%CI 0.40-1.43) QOL decrements, while dose-escalated MHFRT was associated with greater odds of bowel (OR 1.68, 95%CI 1.07-2.61), but not urinary (OR 1.57, 95%CI 0.87-2.85), QOL decrement. Conclusions: Isodose MHFRT and dose-escalated MHFRT both have similar efficacy compared with CFRT, but dose-escalated MHFRT is associated with higher physician-scored and patient-reported bowel and urinary toxicity. Isodose regimens, e.g. 60 Gy in 20 fractions, should be the standard MHFRT regimen for localized prostate cancer.