Are we ready for a paradigm shift from high-dose conventional to moderate hypofractionated radiotherapy in intermediate-high risk prostate cancer? A systematic review of randomized controlled trials with trial sequential analysis

Abstract Aim to evaluate efficacy and late toxicity of moderate hypofractionated (HFRT) over high-dose ( > 76 Gy) conventional radiotherapy (CRT) in a non-inferiority perspective. Methods Randomized controlled trials (RCTs) were included. HFRT regimens were deemed non-inferior to high-dose CRT if the computed CI for the overall RR did not exceed the non-inferiority margin of 7%. Results When the prespecified margin, corresponding to a critical RR of 0.930 for CCS, OS and BFS, was used all efficacy outcomes satisfied the criteria for the non-inferiority analysis indicating the non-inferiority of HFRT regimens over high-dose CRT in the medium term period. Differently, the evidence concerning the late toxicity was inconclusive. Conclusions Noninferiority analysis indicates that moderate HFRT regimes are non-inferior over high-dose CRT in the medium-term. Inconclusive is the evidence for the late toxicity. Longer follow-up will provide a more clear answer concerning the non-inferiority of HFRT regimens in the long-term period.