Genitourinary and gastrointestinal toxicity among patients with localized prostate cancer treated with conventional versus moderately hypofractionated radiation therapy: systematic review and meta-analysis

Background: Hypofractionated (HRT) prostate radiation therapy has the potential to deliver a higher biologically effective dose over a shorter time compared with conventional fractionation (CRT). HRT, giving fewer fractions each with higher dose, might improve the therapeutic ratio, resource use and patient convenience but the toxicity is still controversial. Our objective was to compare the gastroinstestinal (GI) and genitourinary (GU) toxicity of HRT versus CRT.Methods: Systematic review and meta-analysis of randomized clinical trials studies in PubMed, Cochrane and EMBASE databases published through December 2016 was done. Only randomized trials that evaluated patients with localized prostate cancer (PCa) undergoing CRT or HRT were included. In these studies, the daily dose was 1.8Gy or 2Gy per day for CRT and 2.4 to 3.4Gy for HRT.Results: 7317 patients in nine studies were analyzed. Six studies included acute GU toxicity data which showed similar rates for both HRT and CRT (32.6vs. 31.9%; RD 0.00; 95% CI; -0.03,0.03; p=.81; I-2=0%). Similarly, seven studies showed no difference in late GU toxicity based on treatment schedule (28.7 vs. 28.0%; RD -0.01; 95% CI; -0.04,0.03; p=.67; I-2=52%). GI toxicity at three months after radiotherapy was higher in patients treated with HRT in six studies (27.5 vs. 21.9%; RD 0.06; 95% CI; 0.02,0.10; p=.004; I-2=39%); however, eight studies showed GI toxicity 12 months or more after radiotherapy that was statistically the same (12.9 HRT vs. 16.2% CRT; RD -0.01; 95% CI; -0.04,0.02; p=.41; I-2=58%).Conclusion: In meta-analysis of the available randomized trials on moderate HRT versus CRT for prostate cancer, acute and late GU toxicity were similar for both treatment schemes. While HRT was associated with higher acute GI toxicity, late toxicity was similar.