Pd42-07 Actionable Somatic Variants in Prostate Cancer Patients

You have accessJournal of UrologyProstate Cancer: Markers II (PD42)1 May 2024PD42-07 ACTIONABLE SOMATIC VARIANTS IN PROSTATE CANCER PATIENTS Rushil Yagnesh Rawal, Joshua Davood, John Heard, Peris Castaneda Castaneda, and Michael Ahdoot Rushil Yagnesh RawalRushil Yagnesh Rawal , Joshua DavoodJoshua Davood , John HeardJohn Heard , Peris Castaneda CastanedaPeris Castaneda Castaneda , and Michael AhdootMichael Ahdoot View All Author Informationhttps://doi.org/10.1097/01.JU.0001008560.54103.65.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: In recent years there has been an increase in the number of targeted treatments based on molecular/genetic alterations in prostate cancer. With next generation sequencing (NGS), we can assess cancer profiles and identify patient-specific actionable alterations and molecular characteristics which influence treatment outcomes. We sought to identify the frequency of the somatic alterations in prostate cancer. METHODS: The Tempus Lens database was used to assess the frequency of pathogenic somatic alterations or germline alterations in targetable genes (DNA repair, tumor suppressor, cell cycle regulation), elevated microsatellite instability (MSI), androgen receptor alterations (AR), and high tumor mutational burden (TMB) in a contemporary cohort of predominantly advanced prostate cancer patients. Actionable alterations were defined as somatic or germline alterations with a known drug target or known to alter treatment specific outcomes (i.e. MSI/TMB elevations). Targetable somatic alterations were assessed using the 2023 National Comprehensive Cancer Network guidelines, with alteration frequencies calculated based on total gene counts per patient, alone or in combination with other actionable alterations. We sub-stratified patients using clinical staging, disease extent cancer (metastatic vs localized), and Gleason scoring to determine if these factors were likely to correlate with the presence of actionable alterations. RESULTS: A total of 50,976 patients with prostate adenocarcinoma were identified in the database and 12,309 (24.1%) patients had available clinical and DNA data. A total of 3,135 (25.5%) patients demonstrated an actionable somatic alteration, high MSI, or high TMB. Approximately one third of patients (36.5%) displayed multiple actionable somatic alterations. An additional 0.8% of the cohort had a targetable germline alteration. Of the prostate cancer cohort, 3,017 (24.5%) of patients had somatic alterations. TMB and MSI elevations were seen in 11.3% and 9.2% of the population, respectively. However, when patients with known somatic alterations were excluded TMB and MSI elevations were seen in 1.2% and 0.7% of the population, respectively. All 19 somatic alterations are listed in Table 1. CONCLUSIONS: Given the expansion of treatments directed towards molecular and genetic alterations, about a quarter of the high-risk population have actionable somatic variants. Somatic sequencing may add value in evaluating treatment options. As the variety of actionable alterations increases, there is a growing need to identify these alterations for optimal therapeutic selection. Source of Funding: Cedars Sinai Medical Center © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e895 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Rushil Yagnesh Rawal More articles by this author Joshua Davood More articles by this author John Heard More articles by this author Peris Castaneda Castaneda More articles by this author Michael Ahdoot More articles by this author Expand All Advertisement PDF downloadLoading ...