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The following is a summary of “Treatment patterns and outcomes in metastatic castration-resistant prostate cancer patients with and without somatic or germline alterations in homologous recombination repair genes,” published in the February 2024 issue of Oncology by Olmos et al.

Investigating the influence of somatic/germline alterations in homologous recombination repair (HRR) genes on treatment outcomes in metastatic castration-resistant prostate cancer (mCRPC) is essential for refining treatment strategies and improving patient prognosis. In this study, which amalgamates data from four multicenter observational studies involving 729 mCRPC patients, researchers aimed to delve into the prevalence and implications of such alterations, with a particular focus on BRCA1/2 mutations, in patients initiating first-line treatment with androgen receptor signaling inhibitors (ARSi) or taxanes.

Through comprehensive genomic analyses utilizing next-generation sequencing, patients were stratified into distinct subgroups based on the presence or absence of specific HRR alterations. These subgroups included those harboring BRCA1/2 mutations (BRCA), those with HRR mutations excluding BRCA1/2 (HRR non-BRCA), and those devoid of any HRR alterations (non-HRR). Notably, the results revealed compelling differences in treatment outcomes among these subgroups, underscoring the prognostic significance of HRR alterations in mCRPC.

Patients in the BRCA subgroup exhibited notably poorer outcomes across all measured parameters than those in the HRR non-BRCA and non-HRR subgroups. Furthermore, patients in the HRR non-BRCA subgroup displayed inferior outcomes to those in the non-HRR subgroup, indicating a graded effect of HRR alterations on prognosis. These findings emphasize the crucial role of HRR mutations, particularly BRCA1/2, in shaping the clinical course of mCRPC and highlight the necessity for early identification and characterization of such alterations to optimize treatment decisions and patient management.

Moreover, the study provided insights into treatment choice’s impact and alterations’ origin on treatment outcomes in patients with BRCA mutations. Despite the heterogeneity observed within the BRCA subgroup, treatment choice, and alterations’ somatic/germline origin did not significantly influence outcomes, emphasizing the importance of HRR mutations in driving disease progression and treatment response in mCRPC patients.

Overall, these findings underscore the imperative of integrating genomic profiling into clinical practice for personalized risk stratification and treatment optimization in mCRPC, ultimately aiming to enhance patient outcomes and quality of life.

Source: sciencedirect.com/science/article/pii/S0923753424000437