Homologous Recombination and Mismatch Repair Assessment in Men With Advanced Prostate Cancer: A Cross-Sectional Study From a Center in Mexico City

PURPOSE: Metastatic prostate cancer treatment has evolved in the past few decades, finding targeted therapy in the homologous recombination repair (HRR) pathway and mismatch repair (MMR) deficiency. METHODS: This cross-sectional study evaluated men with metastatic prostate cancer treated at a referral center in Mexico City, Mexico. Next-generation sequencing was used. MMR status was evaluated via immunohistochemistry. This study aimed to characterize the genetic landscape in a cohort of Mexican patients. RESULTS: Among 186 patients who underwent somatic testing, 101 also had germline testing. Age at diagnosis was 68 years (range, 41-90), 52.7% had de novo metastatic disease, and 35.5% had metastatic castration-resistant disease. A total of 52 somatic pathogenic variants (PVs) in HRR genes were identified in 45 patients (24.2%); ATM, PALB2, CHEK2, and BRCA2 were the most common. Among 101 individuals with germline genetic testing, 12 (11.8%) carried germline PVs, most frequently in ATM and CHEK2. A higher proportion of germline PV carriers was observed in patients with HRR-positive tumors (28.6% vs 4.1%; P = .001). MMR deficiency was found in 3 out of 140 patients (2.1%). CONCLUSION: Although the overall frequency of PVs is consistent with that reported in other populations, the spectrum of PVs may reflect a distinct molecular profile among Mexican patients with metastatic prostate cancer.