Abstract
OBJECTIVES: While moderately hypofractionated radiotherapy (HFRT) has been recommended as the standard regimen in localized prostate cancer (LPCa) based on non-inferiority trials compared to conventionally fractionated radiotherapy(CFRT), the conclusions on its efficacy and toxicity have not been consistent among all trials. This study aims to systematically compare the efficacy and safety of HFRT with CFRT for LPCa based on the present randomized controlled trials. The longest follow-up data from all the trials were adopted. METHODS AND MATERIALS: This research followed the steps outlined in the PRISMA statement for meta-analyses and systematic reviews. This study presents a meta-analysis of phase III trials comparing CFRT with HFRT for LPCa. The included trials reported relapse-free survival over five years and the incidence of acute or at least 3 years of late gastrointestinal (GI) and genitourinary (GU) toxicity. RESULTS: We were able to include 18 papers in our final analysis. There was no statistically significant difference in relapse-free survival after five years of treatment between the HFRT and CFRT groups. In subgroup analyses, with an α/β of 1.5, a higher equivalent dose of HFRT compared to CFRT is associated with improved relapse-free survival over five years. Acute GI toxicity of Grade 2 or worse was more common in the HFRT group compared to the CFRT group (p < 0.00001). The incidence of acute GI toxicity of Grade 2 or worse rose by 8.78% when moderate HFRT was administered (95% CI = 4.69%-12.87%, p < 0.0001). Subgroup analyses suggested that a single dose of 2.4-3.0 Gy in HFRT may not contribute to an increase in acute GI complications. Moreover, in other outcomes, including acute GI toxicity Grade 3 or worse, acute GU toxicity, and late GI/GU toxicity, no significant differences were observed between the CFRT and HFRT groups. CONCLUSION: The clinical outcomes of HFRT and CFRT were comparable, with similar five-year relapse-free survival, and without different risks of acute or late, severe GI or GU toxicity. HFRT treatment may increase the risk of Grade 2 or worse acute GI toxicity. Thus, proper monitoring and management are required. Less than 3.0 Gy of a single dose or a lower α/β value may be worth considering in the HFRT scheme. Further comprehensive examination of the findings in subgroup analyses is required, such as appropriate dose ranges and management of acute toxicity.