Assessing the association between homologous recombination deficiency scores and treatment response in localized and metastatic prostate cancer

Abstract The aim of this study was to evaluate the predictive value of homologous recombination deficiency scores for therapeutic efficacy in prostate cancer across various disease stages under different regimens. We collected tissue samples from 167 prostate cancer patients and performed genomic sequencing to assess homologous recombination deficiency scores. Among them, 67 patients with localized disease received radical prostatectomy, and 100 patients with metastatic disease received androgen receptor target inhibitor treatment. We examined the predictive value of homologous recombination deficiency scores in forecasting the therapeutic efficacy of standard‐of‐care treatment of prostate cancer under different disease stages. Among patients who underwent radical prostatectomy, those with higher homologous recombination deficiency scores experienced notably shorter biochemical progression‐free survival and overall survival than those with lower scores (median biochemical progression‐free survival: 50.6 versus 148.4 months, p = 0.037; median overall survival: 149.0 months versus not reached, p = 0.0018). In patients receiving androgen receptor pathway inhibitor treatment, men with higher homologous recombination deficiency scores exhibited reduced prostate‐specific antigen progression‐free survival, radiographic progression‐free survival, and overall survival compared to the lower score group at the metastatic castration‐resistant stage (median prostate‐specific antigen progression‐free survival: 8.17 versus 24.17 months, p = 0.032; median radiographic progression‐free survival: 11.8 versus 24.8 months, p = 0.015; median overall survival: 36.5 months versus not reached, p = 0.056) and a deteriorating trend in the metastatic hormone‐sensitive stage. Molecular characterization showed that higher homologous recombination deficiency scores were associated with higher alteration rates in genes such as BRCA2 , CDK12 , MYC , and PTEN . This study reveals that higher homologous recombination deficiency scores are associated with unfavorable treatment efficacy of radical prostatectomy in localized prostate cancer and of androgen receptor target inhibitor treatment in metastatic prostate cancer.