The prognostic significance of homologous recombination repair gene (HRRg) mutations across the different metastatic prostate cancer stages remains unclear. This retrospective real-world study analyzed 162 metastatic castration-sensitive (mCSPC) and 126 castration-resistant (mCRPC) patients from the ProGène database, stratified by HRRg mutational status. Mutation prevalence was similar in both groups (16.0% in mCSPC vs. 13.5% in mCRPC). HRR-positive mCSPC patients had significantly shorter median overall survival (OS) (24.0 months; 95% confidence interval [CI]: 16.0-41.0) compared to HRR-negative patients (45.0 months; 95% CI: 34.0-69.0; P=0.04). Notably, BRCA2-mutated patients exhibited a reduced median OS of 24.0 months (95% CI: 9.0-40.0; P=0.036) and a faster progression free survival compared to HRR-negative patients (median PFS = 8.0 months; 95% CI: 0.0-14.0 vs. 17.0 months; 95% CI: 12.0-20.0; P=0.006). These findings suggest that HRRg mutations-especially BRCA2-are associated with worse prognosis in mCSPC, supporting the value of early genomic screening to guide personalized treatment strategies.
The French journal of urology. 2026 Jun 09 [Epub ahead of print]
Géraldine Cancel-Tassin, Thilina Kariyawasam, Laurène Gautier, Lucile Lefèvre, Olivier Cussenot
Centre de Recherche pour les Pathologies Prostatiques (CeRePP), Paris, France. Electronic address: ., Janssen-Cilag, Issy-les-Moulineaux, France., Centre de Recherche pour les Pathologies Prostatiques (CeRePP), Paris, France.