Pd42-05 Correlating Prostate-Specific Membrane Antigen With Molecular Pathways in Treatment Naïve Prostate Cancer

You have accessJournal of UrologyProstate Cancer: Markers II (PD42)1 May 2024PD42-05 CORRELATING PROSTATE-SPECIFIC MEMBRANE ANTIGEN WITH MOLECULAR PATHWAYS IN TREATMENT NAÏVE PROSTATE CANCER Adam B. Weiner, Raag Agrawal, Nicholas Wang, Ida Sonni, Eric Li, J. J. Zhang, Elai Davicioni, Luca F. Valle, Matthew B. Rettig, Ashley E. Ross, Melvin Lee Kiang Chua, Edward M. Schaeffer, Jeremie Calais, Paul C. Boutros, and Robert E. Reiter Adam B. WeinerAdam B. Weiner , Raag AgrawalRaag Agrawal , Nicholas WangNicholas Wang , Ida SonniIda Sonni , Eric LiEric Li , J. J. ZhangJ. J. Zhang , Elai DavicioniElai Davicioni , Luca F. ValleLuca F. Valle , Matthew B. RettigMatthew B. Rettig , Ashley E. RossAshley E. Ross , Melvin Lee Kiang ChuaMelvin Lee Kiang Chua , Edward M. SchaefferEdward M. Schaeffer , Jeremie CalaisJeremie Calais , Paul C. BoutrosPaul C. Boutros , and Robert E. ReiterRobert E. Reiter View All Author Informationhttps://doi.org/10.1097/01.JU.0001008560.54103.65.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate cancer (PC) is extremely common and biologically diverse - necessitating avenues to further precision care. The advent of PSMA PET has helped augment staging for PC but not all PC is seen on PSMA PET. We hypothesize heterogeneity in PSMA expression might reflect differential tumor biology for treatment naïve PC and could thus be leveraged to help individualize targeted molecular tumor testing and treatment selection. METHODS: First, we correlated PSMA RNA abundance (FOLH1) with SUVmax in a prospective cohort who underwent surgery (NCT03392181; n=55). Using RNA abundance as a proxy for uptake on PET, we then compared differential molecular pathway enrichment using multivariable linear regressions in primary, treatment naïve PC from The Cancer Genome Atlas (TCGA; n=491) with validation in the GRID database (NCT02609269; n=2612). Independent datasets were then assessed to validate correlated pathways and treatment susceptibilities. RESULTS: In NCT03392181, PSMA RNA expression was moderately correlated with SUVmax (Spearman ρ=0.41). A total of 25 hallmark pathways correlated with PSMA expression in the TCGA and GRID cohorts. Importantly, PSMA high tumors tended to be enriched in the androgen response pathway. Accordingly, in a cohort of 178 patients with biochemical recurrence after prostatectomy managed with salvage androgen deprivation therapy alone, patients with PSMA high tumors noted a longer cancer-specific survival (HR 0.55, 95% CI 0.34-0.88; Figure 1). PSMA low tumors were notable for markers of stemness including epithelial mesenchymal transition, angiogenesis, hypoxia, and inflammation. These pathways have been previously associated with resistance to radiotherapy and in a cohort of 248 patients who received primary radiotherapy, those with PSMA low tumors tended to recur sooner (HR 0.50, 95% CI 0.28-0.90). Notably, in a cohort of patients who underwent radical prostatectomy, quartile of PSMA was not associated with time to metastatic recurrence. CONCLUSIONS: Treatment naïve PC with low PSMA may be relatively resistant to hormonal therapy and radiotherapy compared to tumors with high PSMA. Due to these associations, primary surgery should be considered for patients with low PSMA tumors. Download PPT Source of Funding: Simon-Strauss Foundation, UCLA Dr. Allen and Charlotte Ginsburg Fellowship in Precision Genomic Medicine, and the Prostate Cancer Foundation Young Investigator Award (ABW) © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e894 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Adam B. Weiner More articles by this author Raag Agrawal More articles by this author Nicholas Wang More articles by this author Ida Sonni More articles by this author Eric Li More articles by this author J. J. Zhang More articles by this author Elai Davicioni More articles by this author Luca F. Valle More articles by this author Matthew B. Rettig More articles by this author Ashley E. Ross More articles by this author Melvin Lee Kiang Chua More articles by this author Edward M. Schaeffer More articles by this author Jeremie Calais More articles by this author Paul C. Boutros More articles by this author Robert E. Reiter More articles by this author Expand All Advertisement PDF downloadLoading ...