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

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. 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). 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. 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.

Duke Scholars

Author W. Robert Lee Radiation Oncology