PROSTATE cancer is one of the most common cancers worldwide, with significant clinical and healthcare implications. As treatment options continue to evolve, understanding the most effective and least toxic therapies is crucial. A recent study comparing moderately hypofractionated radiotherapy (MHFRT) to conventional radiotherapy (CFRT) provides valuable insights into prostate cancer treatment optimisation, potentially improving patient outcomes while reducing the side effect burden.
The meta-analysis comparing seven Phase 3 trials, including over 5,800 patients, aimed to compare the efficacy and toxicity profiles of two forms of MHFRT: isodose MHFRT and dose-escalated MHFRT, against CFRT for localised prostate cancer. Researchers demonstrated that isodose MHFRT (60 Gy in 20 fractions) offers similar progression-free survival to CFRT without increasing late toxicity. However, dose-escalated MHFRT was associated with a higher risk of bowel side effects. The primary endpoints of the analysis were 5-year progression-free survival and physician-reported late toxicity, including genitourinary and gastrointestinal adverse effects. Patient-reported outcomes, including quality of life assessments for urinary and bowel function, were also evaluated.
The authors found that there were no significant differences in 5-year progression-free survival between the two MHFRT groups and CFRT. The progression-free survival rate for isodose MHFRT was 77.0%, 82.7% for dose-escalated MHFRT, and 75.6% for CFRT, with median follow-up periods of 5.4 years (IQR 4.6–7.2) for isodose MHFRT to 7.1 years (IQR 5.7–8.4) for dose-escalated MHFRT, respectively. Regarding toxicity, no significant differences between groups were observed for Grade 2 or higher genitourinary toxic effects (odds ratio [OR] 1.16; 95% CI: 0.86–1.57; p=0.32 for isodose MHFRT and OR 1.20; 95% CI: 0.95–1.51; p=0.13 for dose-escalated MHFRT). However, dose-escalated MHFRT was associated with significantly higher rates of Grade 2 or higher gastrointestinal side effects (OR 1.48; 95% CI: 1.14–1.92; p=0.0035), compared to isodose MHFRT (OR 1.30; 95% CI: 0.59–2.87; p=0.51). Neither MHFRT regimen was found to reduce urinary quality of life (OR 1.03; 95% CI: 0.51–2.09; p=0.93 for isodose MHFRT and OR 1.57; 95% CI: 0.87–2.85; p=0.13), but dose-escalated MHFRT was observed to reduce bowel quality of life (OR 1.68; 95% CI: 1.07–2.61; p=0.023).
In conclusion, isodose MHFRT demonstrated comparable efficacy to CFRT and posed fewer risks of gastrointestinal toxicity than dose-escalated MHFRT. These results support isodose MHFRT as the preferred approach for localised prostate cancer treatment, reducing treatment time while maintaining high-quality outcomes. However, the study’s limitations include variability in trial design and long-term follow-up data, which could impact generalisability to broader clinical settings.
Reference
Kishan AU et al. Hypofractionated radiotherapy for prostate cancer (HYDRA): an individual patient data meta-analysis of randomised trials in the MARCAP consortium. Lancet Oncol. 2025; DOI: 10.1016/S1470-2045(25)00034-8.
