Ultrahypofractionated versus hypofractionated and conventionally fractionated radiation therapy for localized prostate cancer: A systematic review and meta-analysis of phase III randomized trials

Abstract

IntroductionTo characterize the efficacy (5-year disease-free survival [DFS]) and safety (incidence of grade 2+ late gastrointestinal or genitourinary toxicity) of ultrahypofractionated radiation therapy (UHRT) versus hypofractionated radiation therapy (HFRT) and conventionally fractionated radiation therapy (CFRT) by comparing patients treated on phase III protocols. MethodsA PICOS/PRISMA/MOOSE protocol was used to identify eligible studies. Weighted random effects meta-analyses were conducted using the DerSimonian and Laird method. Wald-type tests were used to compare treatment modalities for each outcome, where the null hypothesis was rejected for p < 0.05. ResultsSeven studies were included that consisted of 6795 patients (2849 CFRT, 3357 HFRT, and 589 UHRT). Median age was 68 years. Summary effect sizes for 5-year DFS were 85.1% (95% CI: 82.1%–87.8%) for CFRT, 86% (95% CI: 83%–88.7%) for HFRT, and 85% (95% CI: 80%–87%) for UHRT (p = 0.66 and p = 0.8 for CFRT vs. HFRT and CFRT versus UHRT, respectively). Summary effect sizes for late grade 2+ gastrointestinal toxicity were 12.1% (95% CI: 9.2%–15.4%) for CFRT, 14.6% (95% CI: 9.9%–20%) for HFRT, and 10% (95% CI: 7%–13%) for UHRT (p = 0.41 and p = 0.09 for CFRT versus HFRT and CFRT versusus UHRT, respectively). Summary effect sizes for late grade 2+ genitourinary toxicity were 19.4% (95% CI: 10.7–29.9%) for CFRT, 20.4% (95% CI: 10.2%–32.9%) for HFRT, and 18% (95% CI: 15%–22%) for UHRT (p = 0.89 and p = 0.92 for CFRT versus HFRT and CFRT versus UHRT, respectively). ConclusionUltrahypofrationated regimens appear to offer similar levels of safety and efficacy to CFRT and HFRT. These findings are hypothesis-generating and require further validation by ongoing prospective trials.