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Impact of homologous recombination repair gene mutations on survival in metastatic prostate cancer: A real-world analysis from an observational database.

Géraldine Cancel-Tassin·Thilina Kariyawasam·Laurène Gautier·Lucile Lefèvre·Olivier Cussenot
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Abstract

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) (24.0months; 95% confidence interval [CI]: 16.0-41.0) compared to HRR-negative patients (45.0months; 95% CI: 34.0-69.0; P=0.04). Notably, BRCA2-mutated patients exhibited a reduced median OS of 24.0months (95% CI: 9.0-40.0; P=0.036) and a faster progression-free survival compared to HRR-negative patients (median PFS=8.0months; 95% CI: 0.0-14.0 vs. 17.0months; 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.

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HumansMaleMutationRetrospective StudiesRecombinational DNA RepairProstatic NeoplasmsAgedPrognosisMiddle AgedNeoplasm MetastasisDatabases, FactualProstatic Neoplasms, Castration-ResistantCancer de la prostateGène de réparation de l’ADN par recombinaison homologueHomologous recombination repair geneMetastasisMétastaseProstate cancerSurvieSurvivalJournal ArticleObservational Study

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Géraldine Cancel-Tassin, Thilina Kariyawasam, Laurène Gautier, Lucile Lefèvre, Olivier Cussenot. 2026-06-09. Impact of homologous recombination repair gene mutations on survival in metastatic prostate cancer: A real-world analysis from an observational database.. https://doi.org/10.1016/j.fjurol.2026.103143

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