Impact of Prostate Radiotherapy on Survival Outcomes in Patients with Metastatic Castration-sensitive Prostate Cancer: A Meta-analysis of Randomized Phase 3 Clinical Trials.

Background and objective: Despite advancements in systemic therapy for metastatic castration-sensitive prostate cancer (mCSPC), the survival benefits of radiotherapy (RT) remain uncertain. This meta-analysis evaluates whether addition of RT to the standard of care (SOC) improves radiographic progression-free (rPFS) and overall (OS) survival, with a focus on systemic therapy intensification.

Methods: A targeted review of three phase 3 trials (HORRAD, STAMPEDE, and PEACE-1) was conducted to assess the role of prostate RT in mCSPC. Two reviewers evaluated study quality, and a meta-analysis using a random-effect model (Review Manager v5.3) analyzed rPFS and OS as the primary outcomes (hazard ratio [HR] with 95% confidence interval [CI]). Subgroup analyses focused on low-volume disease as per the CHAARTED criteria, with heterogeneity assessed via I² and significance set at p < 0.05.

Key findings and limitations: This meta-analysis of 3665 patients from HORRAD, STAMPEDE, and PEACE-1 found that addition of RT to SOC did not improve rPFS or OS in the overall mCSPC population. However, in low-volume disease, RT with SOC and abiraterone acetate (AA) improved rPFS significantly (HR = 0.65, 95% CI: 0.45-0.93; p = 0.02) without an OS benefit. Limitations include pooled data, patient heterogeneity, and variations in treatments and follow-up.

Conclusions and clinical implications: Prostate RT does not improve rPFS or OS in the overall mCSPC population, but offers a significant rPFS benefit in low-volume disease when combined with SOC and AA. Although no OS improvement was observed, the synergy between AA and RT underscores the value of RT for carefully selected patients. Further prospective studies are needed to refine treatment strategies and improve outcomes.