ArticleClinical cancer research : an official journal of the American Association for Cancer Research2025
Association of Homologous Recombination Repair Alterations with Outcomes in Patients with Metastatic Hormone-Sensitive Prostate Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Genetic Predictors of Progression and Skin Rash in Japanese mCSPC Patients Treated With Apalutamide: CUARTET Study.Cancer science · 2026Trial
- Olaparib combined with abiraterone in HRR-mutated metastatic hormone-sensitive prostate cancer: a single-arm phase II trial.World journal of urology · 2026Trial
- Is Prostate Imaging Reporting and Data System equally predictive across racial groups? A narrative review of multiparametric magnetic resonance imaging performance in Black versus White men.Prostate international · 2026Review
- Prevalence and spectrum of homologous recombination repair mutations in patients with metastatic prostate cancer from India.The oncologist · 2026Article
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11 authors.
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Abstract
purposeHomologous recombination/DNA damage repair (HRR) alterations (HRRalt) are found in around 30% of patients with advanced prostate cancer and have been associated with worse prognosis in the metastatic castrate-resistant setting. However, there are limited data with regard to their association with outcomes of patients with metastatic hormone-sensitive prostate cancer (mHSPC). EXPERIMENTAL
designThis study used a de-identified nationwide (U.S.-based) prostate cancer clinico-genomic database. Patients with de novo mHSPC treated with androgen deprivation therapy intensification with either an androgen receptor pathway inhibitor (ARPI) or a taxane who underwent tissue biopsy within 90 days of mHSPC diagnosis were included. Time to castrate resistance (TTCR) and overall survival (OS) were compared between patients with non-altered HRR and those with HRRalt in any of 14 prespecified genes per the olaparib monotherapy FDA label. TTCR and OS indexed from mHSPC diagnosis were evaluated with Cox proportional hazard models adjusted for baseline prognostic factors.
resultsOf 637 eligible patients included in our analysis, 181 harbored HRRalt (28.4%). Compared with patients with non-altered HRR, those with HRRalt had less favorable TTCR when treated with an ARPI [adjusted HR (aHR) = 1.58; 95% confidence interval (CI), 1.17-2.14] or a taxane (aHR = 1.77; 95% CI, 1.3-2.4). Additionally, OS was directionally less favorable in patients with HRRalt (ARPI: aHR = 1.12; 95% CI, 0.80-1.57 and taxane: aHR = 1.23; 95% CI, 0.88-1.72).
conclusionsTo date, this is the largest real-world natural history study evaluating the association of HRRalt with outcomes in the mHSPC setting. These data may inform future clinical trial design and counseling of these patients. See related commentary by Graham and Yu, p. 4001.
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