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ASCO 2023: Can HRR Gene Alterations Predict Prognosis in Metastatic Castration-Resistant Prostate Cancer?

By: Julia Fiederlein Cipriano
Posted: Monday, June 12, 2023

Data regarding the association between homologous recombination repair (HRR) gene alterations and outcomes in patients with metastatic castration-resistant prostate cancer are limited, according to David Olmos, MD, PhD, of the Hospital Universitario 12 de Octubre, Madrid, and colleagues. An analysis, which was presented during the 2023 American Society for Clinical Oncology (ASCO) Annual Meeting (Abstract 5003), investigated the prevalence and outcomes of those with and without such aberrations of somatic and/or germline origin, stratified by BRCA status, who initiated first-line treatment with a novel hormonal therapy or a taxane.

A total of 729 patients from the PROREPAIR-B, PROSENZA, PROSTAC, and PROSABI trials underwent DNA analyses of both somatic and germline alterations in ATM, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, HDAC2, PALB2, RAD51B, and RAD54L using a custom next-generation sequencing panel. Of this population, 30.6% harbored an HRR gene alteration (defined as pathogenic or likely pathogenic variants in at least one allele of at least one gene), including 13.2% who were carriers of BRCA variants.

Patients harboring BRCA variants were found to have significantly worse radiographic progression–free survival (P < .05), progression-free survival 2 (time from randomization to disease progression on second-line therapy; P < .0001), and overall survival (P < .0001) than their non–BRCA-altered counterparts; they also demonstrated significantly worse progression-free survival 2 (P < .05) and overall survival (P < .05) than those with non-BRCA HRR gene alterations. The outcomes between patients with somatic and germline BRCA alterations did not seem to significantly differ.

“It is crucial to screen early for homologous recombination repair [gene alterations], particularly in BRCA1/2, to begin timely, targeted metastatic castration-resistant prostate cancer treatment and improve prognosis,” the investigators concluded.

Disclosure: For full disclosures of the study authors, visit

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