Prevalence of homologous recombination repair genes alterations in metastatic castration-resistant prostate cancer, a multicentric study
Abstract
Introduction: Homologous Recombination Repair (HRR) genes alterations are a resistance mechanism to therapies by taxanes or Androgen Receptor Signalling inhibitors in Metastatic Castration Resistant Prostate Cancer (mCRPC). BRCA-mutated mCRPC patients are eligible to poly adenosine diphosphateribose polymerase inhibitors (PARPi). Therefore, assessing the population-specific prevalence of HRR-related genes alterations is of public healthcare importance. Methods: This retrospective, non-interventional, multicentric study was conducted across 6 reference French centers in a \"real-life\" setting. 788 paraffin-embedded mCRPC patient-samples were included and submitted to testing for BRCA1/2 in six different centers; additionally, non-BRCA HRR-related genes were investigated in two different centers. Results: Among the samples, n=602 (76.4%) were contributive for molecular testing. In multivariate analysis by logistic regression and sensitivity analysis, only sample age (P<0.01), sample surface area (P=0.02) and institution (P=0.018) remained statistically significant. BRCA alterations were detected in n=39/602 (6.5%) of contributive samples, with n=35 and n=4 alterations of BRCA2 and BRCA1 respectively. Non-BRCA HRR-related genes alterations were detected in n=12/157 (7.6%) of contributive samples, with alterations of mainly ATM (n=6, 3.8%), CDK12 (n=4, 2.5%) and CHEK2 (n=2, 1.3%). Discussion: In this study, testing contributivity was similar or higher that of other studies in the literature, and observed mutations prevalences were similar to that of other screenings of western populations. Harmonising per-centres protocols and enhancing molecular testing contributivity with the screening of circulating DNA samples and expanding its range by including non-BRCA HRR-related genes in all reference centres will enable more patients to be accurately treated by targeted therapies. Level of evidence: 3 (grade C).
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BibTeX
@article{allaume2026prevalence,
title = {{Prevalence of homologous recombination repair genes alterations in metastatic castration-resistant prostate cancer, a multicentric study}},
author = {Pierre Allaume and Maxime Raby and Maya Nourieh and Alexandra Lespagnol and Anne Tallet and Sarah Péricart and Juliet Tantot and Véronique Lindner and Myriam Decaussin-Petrucci and Celine Callens and Françoise Descôtes and Yves Allory and Nathalie Rioux-Leclercq and Solène-Florence Kammerer-Jacquet and Gaëlle Fromont-Hankard},
journal = {The French Journal of Urology},
year = {2026},
month = oct,
doi = {10.1016/j.fjurol.2026.103148},
url = {https://hal.science/hal-05675870v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Prevalence of homologous recombination repair genes alterations in metastatic castration-resistant prostate cancer, a multicentric study
AU - Pierre Allaume
AU - Maxime Raby
AU - Maya Nourieh
AU - Alexandra Lespagnol
AU - Anne Tallet
AU - Sarah Péricart
AU - Juliet Tantot
AU - Véronique Lindner
AU - Myriam Decaussin-Petrucci
AU - Celine Callens
AU - Françoise Descôtes
AU - Yves Allory
AU - Nathalie Rioux-Leclercq
AU - Solène-Florence Kammerer-Jacquet
AU - Gaëlle Fromont-Hankard
PY - 2026
DA - 2026/10/14
JO - The French Journal of Urology
DO - 10.1016/j.fjurol.2026.103148
UR - https://hal.science/hal-05675870v1
AB - Introduction: Homologous Recombination Repair (HRR) genes alterations are a resistance mechanism to therapies by taxanes or Androgen Receptor Signalling inhibitors in Metastatic Castration Resistant Prostate Cancer (mCRPC). BRCA-mutated mCRPC patients are eligible to poly adenosine diphosphateribose polymerase inhibitors (PARPi). Therefore, assessing the population-specific prevalence of HRR-related genes alterations is of public healthcare importance. Methods: This retrospective, non-interventional, multicentric study was conducted across 6 reference French centers in a \"real-life\" setting. 788 paraffin-embedded mCRPC patient-samples were included and submitted to testing for BRCA1/2 in six different centers; additionally, non-BRCA HRR-related genes were investigated in two different centers. Results: Among the samples, n=602 (76.4%) were contributive for molecular testing. In multivariate analysis by logistic regression and sensitivity analysis, only sample age (P<0.01), sample surface area (P=0.02) and institution (P=0.018) remained statistically significant. BRCA alterations were detected in n=39/602 (6.5%) of contributive samples, with n=35 and n=4 alterations of BRCA2 and BRCA1 respectively. Non-BRCA HRR-related genes alterations were detected in n=12/157 (7.6%) of contributive samples, with alterations of mainly ATM (n=6, 3.8%), CDK12 (n=4, 2.5%) and CHEK2 (n=2, 1.3%). Discussion: In this study, testing contributivity was similar or higher that of other studies in the literature, and observed mutations prevalences were similar to that of other screenings of western populations. Harmonising per-centres protocols and enhancing molecular testing contributivity with the screening of circulating DNA samples and expanding its range by including non-BRCA HRR-related genes in all reference centres will enable more patients to be accurately treated by targeted therapies. Level of evidence: 3 (grade C).
SN - 2950-4201
SN - 2950-3930
ER -