Hypofractionated and dose-boosted radiotherapy improves metastasis-free survival in clinically localised prostate cancer

This systematic review and meta-analysis examined the efficacy and safety of hypofractionated and dose-boosted radiotherapy fractionation schedules compared to standard radiotherapy for patients with clinically localised prostate cancer. The analysis included a total sample size of 12,479 patients. The setting and specific publication details were not reported in the source data. The review focused on comparing different fractionation schedules to determine their impact on survival outcomes and adverse event rates.

The primary outcomes assessed included biochemical recurrence-free survival, metastasis-free survival, overall survival, and rates of grade 2 or 3 adverse events. Results for metastasis-free survival showed a significant improvement with the combination of external beam radiotherapy with brachytherapy or with focal boost. The effect size for this outcome was a hazard ratio of 0.76. This result was based on absolute numbers of n = 1468. The 95% confidence interval ranged from 0.6 to 0.95 with a p-value of 0.016.

Analysis of overall survival indicated a possible benefit in a sensitivity analysis that included two studies with extended follow-up. The effect size for overall survival was a hazard ratio of 0.75. This finding was derived from absolute numbers of n = 897. The 95% confidence interval was 0.6 to 0.95 with a p-value of 0.016. For biochemical recurrence-free survival, the review observed a small numerical improvement. The effect size was a hazard ratio of 0.88 based on absolute numbers of n = 10220. The 95% confidence interval was 0.76 to 1 with a p-value of 0.058.

Safety and tolerability findings revealed that acute grade 2 gastrointestinal adverse events were modestly increased with moderate hypofractionation. Acute grade 3 genitourinary adverse events were increased with ultra-hypofractionation. No significant differences were observed in late adverse events. Serious adverse events, discontinuations, and specific tolerability metrics were not reported in the source data.

Methodological limitations included concerns regarding risk of bias associated with patient allocation in the dose-boost analysis. The impact of open-label study designs on adverse event reporting was also identified as a limitation. Funding sources and conflicts of interest were not reported. These factors may influence the interpretation of the results and the generalizability of the findings to broader clinical practice.

Practice relevance suggests that findings support the use of dose-boosting as a means to improve survival in high-risk patients. Hypofractionation is supported as a method to reduce treatment time associated with a potential improvement in disease control. These results compare to prior landmark studies by providing pooled data that may inform treatment selection for patients with clinically localised disease.

Several questions remain unanswered regarding the long-term durability of these survival benefits and the optimal balance between treatment time reduction and toxicity profiles. The lack of reported data on serious adverse events and discontinuations limits the ability to fully assess the risk-benefit ratio in specific subgroups. Clinicians must weigh the potential survival improvements against the increased risk of acute adverse events when considering these fractionation schedules.