Pd42-03 Understanding Population-Wide Genomic Risk Distribution and Integrating Clinical-Genomic Risk for Prognostication in Prostate Cancer

You have accessJournal of UrologyProstate Cancer: Markers II (PD42)1 May 2024PD42-03 UNDERSTANDING POPULATION-WIDE GENOMIC RISK DISTRIBUTION AND INTEGRATING CLINICAL-GENOMIC RISK FOR PROGNOSTICATION IN PROSTATE CANCER Udit Singhal, Ralph Jiang, Matthew Schipper, James Proudfoot, Elisabeth Chase, Krithika Suresh, Elai Davicioni, William C. Jackson, Daniel E. Spratt, Robert T. Dess, and Todd M. Morgan Udit SinghalUdit Singhal , Ralph JiangRalph Jiang , Matthew SchipperMatthew Schipper , James ProudfootJames Proudfoot , Elisabeth ChaseElisabeth Chase , Krithika SureshKrithika Suresh , Elai DavicioniElai Davicioni , William C. JacksonWilliam C. Jackson , Daniel E. SprattDaniel E. Spratt , Robert T. DessRobert T. Dess , and Todd M. MorganTodd M. Morgan View All Author Informationhttps://doi.org/10.1097/01.JU.0001008560.54103.65.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Genomic classifiers (GC) are endorsed by national guidelines and are commonly used to inform prognosis in patients with prostate cancer (PCa). Despite their availability, integration of GCs within optimized clinical prognostic stage group systems are lacking. Therefore, using two prospective population-based tumor registries, we aimed to understand the distribution of genomic risk within the previously validated, American Joint Committee on Cancer (AJCC)-compliant, staging collaboration for cancer of the prostate (STAR-CAP). We hypothesized that genomic heterogeneity would have implications on clinical risk estimates and may inform treatment options. METHODS: Genomic risk distribution was assessed using the Decipher GC (Veracyte, San Diego, CA) in two separate multi-institutional, prospectively collected population-based tumor registries: (1) the Decipher Genomics Resource for Intelligent Discovery (GRID) and (2) the community-based Michigan Urological Surgery Improvement Collaborative (MUSIC) (n=50,981 GRID+1584 MUSIC). Our primary endpoint was PCa-specific mortality (PCSM) with a secondary endpoint of distant metastasis (DM). Marginal risk estimates provided by STAR-CAP stage were combined with hazard ratios of Decipher on PCSM and DM along with the distribution of Decipher scores by STAR-CAP stage to calculate integrated estimates. RESULTS: Median age was 68 years and 66 years and median PSA was 6.2 and 10.5 ng/mL in the GRID and MUSIC populations, respectively. The GRID population had 31.4%, 18.5%, and 50.2%, with high-, intermediate-, and low-Decipher risk, compared to 35.7%, 16.2%, and 47.9% in MUSIC. Decipher-based genomic risk varied across all STAR-CAP stages (IA-IIIC) in both the Decipher GRID and MUSIC registries. Among those with low STAR-CAP stage (IA-IC), there was a proportion of men with high genomic risk in both GRID (18.7%) and MUSIC (17.7%) populations. Estimates of PCSM (0.1% to 49.2%) and DM (0.3%-73.4%) varied widely depending on clinical-genomic risk. Use of a Decipher-informed STAR-CAP system led to a significant degree of stage reclassification, including 25.6% or 45.5% upstaging or downstaging at least one stage and 7.2% or 11.8% upstaging or downstaging at least two stages, respectively. CONCLUSIONS: In a large scale, population-based, prospective assessment, we found wide variation in genomic risk distribution in clinical stage groups, suggesting integration of genomic and clinicopathologic risk groups may lead to more nuanced prediction of relevant clinical outcomes in PCa. Source of Funding: Urology Care Foundation, Prostate Cancer Foundation © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e893 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Udit Singhal More articles by this author Ralph Jiang More articles by this author Matthew Schipper More articles by this author James Proudfoot More articles by this author Elisabeth Chase More articles by this author Krithika Suresh More articles by this author Elai Davicioni More articles by this author William C. Jackson More articles by this author Daniel E. Spratt More articles by this author Robert T. Dess More articles by this author Todd M. Morgan More articles by this author Expand All Advertisement PDF downloadLoading ...