Moderate hypofractionated radiotherapy vs conventional fractionated radiotherapy in localized prostate cancer: a systemic review and meta-analysis from Phase III randomized trials

To determine the efficacy and late toxicities of moderate (2.5-4 Gy) hypofractionated radiotherapy (H-RT) in localized prostate cancer, a meta-analysis of published randomized clinical trials comparing moderate H-RT with conventional fractionated RT (C-RT) was performed. Systematic search on published randomized clinical trials in English according to Cochrane review guidelines in databases of Pubmed, Embase, Cochrane, web of science, and Wiley Online Library was carried out. Outcomes of interests were biochemical and clinical disease failure (BCDF), biochemical failure (BF), overall survival (OS), and late toxicities. Seven of the 365 studies fulfilled inclusion criteria with 8,156 participants. Compared with C-RT, moderate H-RT showed a lower BF rate (risk ratio [RR] =0.80, 95% CI: 0.68-0.95, =0.009), while did not improve OS (RR =0.68, 95% CI: 0.78-1.02, =0.10). There was no significant difference in BCDF rates between H-RT and C-RT (RR =0.92, 95% CI: 0.82-1.02, =0.12). The H-RT was deeply grouped into dose-escalated H-RT (with a higher biologically effective dose [BED ] than C-RT) and no dose-escalated H-RT; dose-escalated H-RT significantly decreased BCDF rate compared with C-RT (RR =0.84, 95% CI: 0.73-0.96, =0.01). Regarding late toxicities, there is no significant difference in late gastrointestinal (GI; RR =0.97, 95% CI: 0.71-1.33, =0.85) and genitourinary (GU) toxicities (RR =1.04, 95% CI: 0.87-1.24, =0.69). When subgrouped into dose-escalated H-RT (with a higher BED compared with C-RT) and no dose-escalated H-RT, dose-escalated H-RT increased GI toxicity (RR =1.62, 95% CI: 1.26-2.09, =0.0002) and GU toxicity (RR =1.28, 95% CI: 1.05-1.55, =0.01), while no dose-escalated H-RT significantly lowered GI toxicity (RR =0.81, 95% CI: 0.70-0.94, =0.005) and placed no influence on GU toxicity (RR =1.02, 95% CI: 0.88-1.20, =0.77). This meta-analysis provides reliable evidence that moderate H-RT decreases BF rate, while does not improve OS. Compared with C-RT, H-RT with an increase in BED improved BCDF rates significantly, and accordingly, an increase in BED will result in elevated late GI and GU toxicities.