Abstract 5787: Mutation prevalence in metastatic castration-sensitive prostate cancer based on metastasis timing and risk stratification

Abstract Introduction and Objectives: Metastatic castration-sensitive prostate cancer (mCSPC) is a clinically heterogeneous disease in which genetic mutations and tumor burden influence patient outcomes. Mutations in some DNA repair genes (e.g. BRCA1/2 and ATM) have been related to prostate cancer development and progression and may serve as therapeutic targets. The GENPRO12 study aims to evaluate the mutational profiles in non-mCSPC and mCSPC patients and to explore its clinical associations. Material and Methods: This preliminary report includes 109 mCSPC patients, stratified by synchronous/metachronous disease. Each group was further classified into risk/volume (high/low) categories based on CHAARTED and LATITUDE criteria. Tumor samples were collected and analyzed using next-generation sequencing (NGS) ACHILLES test (Olmos et al. Ann Oncol 2024) to identify mutations in 40 genes, including BRCA1/2, ATM, and other prostate cancer-related genes. Clinicopathological data were extracted from medical records. Results: Median age at diagnosis of mHSPC was 72 (range 47-92) with a median PSA 46.9 (0.3-3956). 90 patients had synchronous metastatic disease, 69 were CHAARTED high-volume, 76 were LATITUDE high-risk, and 25 had visceral metastases (17 in the lung only). All but 11 patients had at least 1 alteration in the genes analyzed. The most relevant altered genes are listed in the table. BRCA2, PTEN, RB1 Loss of Function (LoF) and MYC gain were more frequent in de novo and/or high-volume cases. Conclusions: Genetic alterations with prognostic and/or predictive value can be detected using prostate-specific NGS assays on archived diagnostic FFPE samples. Their prevalence may vary based on mCSPC clinical presentation, reflecting distinct disease biologies. Updated results, including outcomes and treatment responses, will be presented at the meeting. Citation Format: María Ovejero-Sánchez, Ana Jambrina, Ignacio González-Ginel, Daniel Tello, Manuel Balongo, Ana Gutierrez-Pecharroman, Pedro P López-Casas, Alfredo Rodríguez-Antolín, Elena Castro, David Olmos. Mutation prevalence in metastatic castration-sensitive prostate cancer based on metastasis timing and risk stratification [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5787.