Background: Treatment for metastatic castration-resistant prostate cancer (mCRPC) harboring homologous recombination repair (HRR) alteration remains a challenge. Recently published trials have evaluated the poly (ADP-ribose) polymerase inhibitors (PARPIs) in mCRPC. However, the efficacy in subgroup with specific HRR gene mutation and treatment protocol requires further elucidation. This meta-analysis aims to explore the efficacy of PARPIs based on subgroups and reconstructed individual patient data (IPD). Methods: Literature was searched using PubMed, Embase, Cochrane Library, and ClinicalTrials.gov up to April 2025. The primary outcome was radiographic progression-free survival (rPFS), and the secondary outcomes included overall survival (OS), prostate-specific antigen progression-free survival (PSA-PFS), and adverse events (AEs). Hazard ratios (HRs) and risk ratios (RRs) were pooled as the indicators using inverse-variance and Mantel-Haenszel methods. IPD was reconstructed from Kaplan–Meier curve. Survival analysis was performed using Cox proportional hazards model based on the reconstructed IPD. Heterogeneity was assessed by I2 and sensitivity analysis. Publication bias was examined via contour‑enhanced funnel plots. Results: Data of 1840 mCRPC patients with HRR alteration from five pivotal phase III clinical trials were analyzed. PARPIs significantly improved overall rPFS (HR: 0.55) and OS (HR: 0.85). PARPIs also prolonged rPFS across the subgroups defined by clinicopathologic features. In BRCA1/2 subgroup, survival benefits were prominent for rPFS (HR 0.32) and OS (HR 0.70). For patients with non- BRCA alterations, no benefits of PARPIs were detected for rPFS and OS in ATM subgroup, and for OS in CDK12 subgroup. Survival analyses indicated that PARPIs treatment was significantly associated with the improved rPFS (HR: 0.73, P < 0.001) and PSA-PFS (HR: 0.80, P = 0.020) in the overall population, and revealed OS benefit in BRCA1/2 subgroup (HR: 0.77, P = 0.030). Comparing with monotherapy, combination regimen of PARPIs provided greater benefits for rPFS (HR: 0.56, P < 0.001)and OS (HR: 0.64., P < 0.001). Conclusions: PARPIsimprove survival in mCRPC patients with BRCA1/2 mutation, but have no effect in those with ATM mutation. Comparing with PARPIs monotherapy, the combination regimen provides greater survival benefit in the overall population. Future investigation should validate these findings in real-world settings.

Background Recently published phase III clinical trials documented that darolutamide could improve the prognosis of patients with metastatic hormone-sensitive prostate cancer (mHSPC). This meta-analysis aims to assess the efficacy of darolutamide in mHSPC based on subgroups and reconstructed individual-level data. Methods Literature was searched using PubMed, Embase, Cochrane Library and ClinicalTrials.gov. The primary outcome was overall survival (OS), while the secondary outcomes included risk to castration-resistant prostate cancer (CRPC) and adverse event. The risk ratio (RR) with 95% confidence interval (CI) was selected as effect size. Survival analysis was performed using Kaplan-Meier method and Cox hazards model based on the reconstructed individual patient data (IPD). Z test and Bonferroni correction were applied for the comparison between subgroups. I² ≤ 50% was regarded as low heterogeneity. Results The data of 1974 patients from two III phase trials, ARASENS and ARANOTE, were analyzed. For 1-year OS, the risk of death was 0.56 (95% CI: 0.41–0.78) in the darolutamide group comparing with the placebo group. The risk of death were 0.76 (95% CI: 0.64–0.91) and 0.75 (95% CI: 0.67–0.85) in the darolutamide group for 2-year OS and 3-year OS respectively. Darolutamide also decreased the risk of progression to CRPC within 3 years. Moreover, darolutamide demonstrated consistent OS benefits across different subgroups stratified by demographic and clinical characteristics with acceptable safety profile. Survival analyses demonstrated darolutamide improved OS and delayed disease progression even after adjusting for background therapy. Conclusions Darolutamide provides survival benefits and postpones the progression from mHSPC to the castration-resistant phase. The consistent efficacy across subgroups suggest that darolutamide could be a promising addition to combination therapy for mHSPC. Further investigation using original IPD is warranted to confirm these findings.

Recently, several trials have explored the efficacy of salvage radiotherapy (RT) alone or in combination with androgen deprivation therapy (ADT) in patient