You have accessJournal of UrologyCME1 Apr 2023MP17-01 DIFFERENTIAL TRANSCRIPTOMIC INDICATORS OF POTENTIAL THERAPEUTIC RESPONSE TO TARGETED THERAPY FOR AJCC IIC+ LOCALIZED PROSTATE CANCER WITH DECIPHER ≥0.95 Eric Li, James Proudfoot, Alex Hakansson, Xin Zhao, Yang Liu, Adam Weiner, Edward Schaeffer, Elai Davicioni, and Ashley Ross Eric LiEric Li More articles by this author , James ProudfootJames Proudfoot More articles by this author , Alex HakanssonAlex Hakansson More articles by this author , Xin ZhaoXin Zhao More articles by this author , Yang LiuYang Liu More articles by this author , Adam WeinerAdam Weiner More articles by this author , Edward SchaefferEdward Schaeffer More articles by this author , Elai DavicioniElai Davicioni More articles by this author , and Ashley RossAshley Ross More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003237.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Among patients with AJCC Stage IIC+ cancer, a subset of patients are genomically at highest risk of progression with very high Decipher ≥0.95 scores. This group of patients is distinct and not present with AJCC I-IIB prostate cancer. As genomic changes may predict potential benefit from molecular based therapies, we sought to identify incidence of genomic alterations in this population. METHODS: We analyzed the transcriptomes of 13,117 men diagnosed with AJCC stage IIC+ localized prostate cancer. We compared signature readouts for androgen receptor activity (AR-A), PTEN loss, homologous repair deficiency, Rb loss, immune activity, and PSMA (FOLH1) expression, as well as prostate subtyping classifier (PSC) based on cell of origin and molecular pathways. Standardized mean differences (SMD) were calculated to compare size effect, with significant effect size defined as 0.2. RESULTS: 1767 men with AJCC Stage IIC+ cancer were found to have Decipher score ≥0.95. Patients with Decipher ≥0.95 possessed lower AR activity, as well as higher rates of PTEN loss and HR deficiency compared to men with high Decipher 0.6-0.95 (SMD 0.32, 0.40, and 0.43). There was a lower incidence of luminal differentiated (LD), and higher incidence of basal immune (BI) and basal neuroendocrine (BN) subtypes among those with Decipher ≥0.95. Rates of Rb loss remained low across all Decipher subgroups, and there was no significant difference in FOLH1 expression comparing men with Decipher 0.6-0.95 and Decipher ≥0.95. CONCLUSIONS: Patients with very high Decipher ≥0.95 localized prostate cancer have a distinct molecular profile, and may benefit from PARP inhibitors. Further investigation is required to understand how these molecular signatures may drive progression and metastasis in patients who are identified as very high risk on genomic classifier testing. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e212 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Eric Li More articles by this author James Proudfoot More articles by this author Alex Hakansson More articles by this author Xin Zhao More articles by this author Yang Liu More articles by this author Adam Weiner More articles by this author Edward Schaeffer More articles by this author Elai Davicioni More articles by this author Ashley Ross More articles by this author Expand All Advertisement PDF downloadLoading ...