Pd01-01 Germline Pathogenic Variants in Patients With Prostate Cancer: Results From the Technology-Enhanced Acceleration of Germline Evaluation for Therapy (Target) Study

You have accessJournal of UrologyProstate Cancer: Advanced (including Drug Therapy) I (PD01)1 May 2024PD01-01 GERMLINE PATHOGENIC VARIANTS IN PATIENTS WITH PROSTATE CANCER: RESULTS FROM THE TECHNOLOGY-ENHANCED ACCELERATION OF GERMLINE EVALUATION FOR THERAPY (TARGET) STUDY Stacy Loeb, Laura Gross, Heather Cheng, Adrian Rivera, Scott Keith, Nataliya Byrne, Tatiana Sanchez Nolasco, and Veda Giri Stacy LoebStacy Loeb , Laura GrossLaura Gross , Heather ChengHeather Cheng , Adrian RiveraAdrian Rivera , Scott KeithScott Keith , Nataliya ByrneNataliya Byrne , Tatiana Sanchez NolascoTatiana Sanchez Nolasco , and Veda GiriVeda Giri View All Author Informationhttps://doi.org/10.1097/01.JU.0001009540.33579.43.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The TARGET study was a randomized trial comparing pre-test genetic education through a webtool versus traditional genetic counseling (NCT 04447703) for patients with prostate cancer who meet histologic or family history criteria for germline testing. The objective of this study was to characterize pathogenic variants (PVs) identified among participants in the trial. METHODS: Participants in the TARGET randomized trial who elected for genetic testing underwent a custom 51-gene panel from Invitae. Descriptive statistics were used to summarize the characteristics of patients with PVs. RESULTS: Among 266 participants in the TARGET study who underwent germline testing, 42 (15.7%) had PVs, 87 (32.7%) had variants of uncertain significance only, and 137 (51.5%) had negative results. The following PVs were identified: 8 BRCA2, 6 ATM, 5 in Fanconi Anemia (FA) genes (2 FANCA, 2 FANCM, 1 FANCD2), 5 APC, 4 CHEK2, 2 BRCA1, 2 MSH6, 1 BLM, 1 NBN, 1 PALB2, 1 RAD51C, 1 WRN, and 8 MUTYH carriers. The median age at diagnosis was 64 years (range 46-76) among all participants with PVs, and Gleason score was 6 for 15%, 7 for 41%, and 8-10 in 44%. For patients with FA gene mutations, 20% had Gleason >=8 and the rest had Gleason 7 disease with median age at diagnosis of 58.5 years (range 46-65 years). CONCLUSIONS: Pathogenic germline variants were identified in 15.7% of study participants, which is higher than in some other published studies. This is likely related to the use of a more comprehensive 51-gene panel in our study, as several of these genes are not on standard prostate cancer panels and some PVs were in genes without a known association to prostate cancer (such as APC and MUTYH) though they do have clinical actionability for other cancers. Of note, FA genes may be important to include on prostate cancer germline panels given trends for younger age at diagnosis and potential biologic relevance for targeted therapy in the future. Further study is warranted into the clinical significance and downstream outcomes. Source of Funding: Prostate Cancer Foundation © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e62 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Stacy Loeb More articles by this author Laura Gross More articles by this author Heather Cheng More articles by this author Adrian Rivera More articles by this author Scott Keith More articles by this author Nataliya Byrne More articles by this author Tatiana Sanchez Nolasco More articles by this author Veda Giri More articles by this author Expand All Advertisement PDF downloadLoading ...