Real-world genetic testing patterns in metastatic prostate cancer in Latin American (LATAM) population.

Abstract

e17055 Background: Prostate cancer (PC) clinical course is variable. It was thought that BRCA1 and BRCA2 mutations were associated with only a small proportion of PC cases. However, recent genomic analysis has revealed that germline or somatic inactivating mutations in genes involved in the homologous recombination (HR) pathway of DNA repair collectively occur in as much as 20%-25% of advanced PC. Referring to the metastatic castration resistant PC (mCRPC) the somatic mutations were recently reported to be up to 12,7% for BRCA2 and 2% for BRCA1. PC is the most frequent tumor among LATAM men. The incidence of de novo metastatic PC is higher in LATAM than other parts of the world, and demographic changes in the region have increased disease burden. However, region-specific information about genomic profiling of this tumor is scant. This study aims to describe the genomic profile patterns of PC, either presenting as metastatic hormone treatment–naive prostate cancers, or locoregional tumors that later evolve to metastatic disease in LATAM pts. Methods: A retrospective observational cohort design was used. The study sample included patients with a confirmed PC diagnosis with adenocarcinoma histology, from 8 academic centers in 3 countries between 1st January 2020 and 30th November 2022 whom had been molecularly tested. Results: Of 185 pts tested, 183 had metastatic PC. Somatic evaluation was done in 49.5% of the pts, while 66.48% have germline test, 13% pts were tested by both methods. Forty-two (22.7%) pts were tested in the metastatic sensitive castration scenario, instead 141 (76.2%) were mCRPC. Actionable mutations were detected in 21 pts (11.35%), being the most frequents PTEN and BRCA2. The median tumor mutational burden was 5 (IQR 0-2.52). No mutation in the following clinically relevant genes were found in our pts: BRCA1, RAD51C, RAD51D, RAD54, PALB2 and BRIP1 (Table1). Between pts with actionable mutations, 27.3% had high volume disease, with a median Gleason score of 9 (IQR 8-9) and de novo metastatic setting in 40.9%. Despite that 25.9% of our pts have a VUS (Variant of unknown significance), only 7 pts (3.8%) access to oncology genomic counseling. Conclusions: In our region, the percentage of actionable mutations found in this population appears to be lower than that reported in studies from other regions of the world, but remarkably the mutations detected are different. This data shows the importance to have mutational data of the population of each region what is heterogeneous among themselves and with respect to other regions of the world. [Table: see text]