Conventional Versus Hypofractionated Radiation Therapy for Localized or Locally Advanced Prostate Cancer: A Systematic Review and Meta-analysis along with Therapeutic Implications

Abstract

A systematic review and meta-analysis were conducted to evaluate the therapeutic outcomes of conventional radiation therapy (CRT) and hypofractionated radiation therapy (HRT) for localized or locally advanced prostate cancer (LLPCa). A total of 599 abstracts were extracted from 5 databases and screened in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Only phase III trials randomized between CRT and HRT in LLPCa with a minimum of 5years of follow-up data were considered. The evaluated endpoints were biochemical failure, biochemical and/or clinical failure, overall mortality, prostate cancer-specific mortality, and both acute and late gastrointestinal (GI) and genitourinary (GU) (grade ≥2) toxicity. Ten trials from 9 studies, with a total of 8146 patients (CRT, 3520; HRT, 4626; 1 study compared 2 HRT schedules with a common CRT regimen), were included in the evaluation. No significant differences were found in the patient characteristics between the 2 arms. However, the RT parameters differed significantly between CRT and HRT (P<.001 for all). The use of androgen deprivation therapy varied from 0% to 100% in both groups (mean±standard deviation 43.3%±43.6% for CRT vs HRT; P=NS). The odds ratio, risk ratio, and risk difference (RD) between CRT and HRT for biochemical failure, biochemical and/or clinical failure, overall mortality, prostate cancer-specific mortality, acute GU toxicity, and late GU and GI toxicities were all nonsignificant. Nevertheless, the incidence of acute GI toxicity was 9.1% less with CRT (RD 0.091; odds ratio 1.687; risk ratio 1.470; P<.001 for all). On subgroup analysis, the patient groups with ≤66.8% versus >66.8% androgen deprivation therapy (RD 0.052 vs 0.136; P=.008) and <76% versus ≥76% full seminal vesicles in the clinical target volume (RD 0.034 vs 0.108; P<.001) were found to significantly influence the incidence of acute GI toxicity with HRT. HRT provides similar therapeutic outcomes to CRT in LLPCa, except for a significantly greater risk of acute GI toxicity. HRT enables a reduction in the overall treatment time and offers patient convenience. However, the variables contributing to an increased risk of acute GI toxicity require careful consideration.