Toxicity after moderately hypofractionated versus conventionally fractionated prostate radiotherapy: A systematic review and meta-analysis of the current literature

Background: Moderately hypofractionated radiotherapy (RT) currently represents the standard RT approach for all prostate cancer (PCa) risk categories. We performed a systematic review and meta-analysis of available literature, focusing on acute and late genitourinary (GU) and gastrointestinal (GI) adverse events (AEs) of moderate hypofractionation for localized PCa. Materials and methods: Literature search was performed and two independent reviewers selected the records according to the following Population (P) Intervention (I) Comparator (C) and Outcomes (O) (PICO) question: “In patients affected by localized PCa (P), moderately hypofractionated RT (defined as a treatment schedule providing a single dose per fraction of 3–4.5 Gy) (I) can be considered equivalent to conventionally fractionated RT (C) in terms of G > 2 GI and GU acute and late adverse events (O)?”. Bias assessment was performed using Cochrane Cochrane Collaboration's Tool for Assessing Risk of Bias. Results: Thirteen records were identified and a meta-analysis was performed. Risk of acute GI and GU > 2 adverse events in the moderately hypofractionated arm was increased by 9.8 % (95 %CI 4.8 %–14.7 %; I2 = 57 %) and 1.5 % (95 % CI -1.5 %-4.4 %; I2 = 0%), respectively. Discussion: Overall, majority of trials included in our meta-analysis suggested that moderately hypofractionated RT is equivalent, in terms of GI and GU adverse events, to conventional fractionation. Pooled analysis showed a trend to increased GI toxicity after hypofractionated treatment, but this might be related to dose escalation rather than hypofractionation.