MP16-12 INTEGRATED GENE EXPRESSION PROFILING AND TARGETED PANEL SEQUENCING TO IMPROVE TREATMENT SELECTION IN NON-MUSCLE INVASIVE BLADDER CANCER

Abstract

You have accessJournal of UrologyBladder Cancer: Non-invasive II (MP16)1 Sep 2021MP16-12 INTEGRATED GENE EXPRESSION PROFILING AND TARGETED PANEL SEQUENCING TO IMPROVE TREATMENT SELECTION IN NON-MUSCLE INVASIVE BLADDER CANCER Jeffrey Damrauer, Kyle Roell, Markia Smith, Xuezheng Sun, Erin Kirk, Katherine Hoadley, Halei Benefield, Gopa Iyer, David Solit, Matthew Milowsky, William Kim, Matthew Nielsen, Sara Wobker, Guido Dalbagni, Hikmat Al-Ahmadie, Andrew Olshan, Bernard Bochner, Helena Furberg, Melissa Troester, and Eugene Pietzak Jeffrey DamrauerJeffrey Damrauer More articles by this author , Kyle RoellKyle Roell More articles by this author , Markia SmithMarkia Smith More articles by this author , Xuezheng SunXuezheng Sun More articles by this author , Erin KirkErin Kirk More articles by this author , Katherine HoadleyKatherine Hoadley More articles by this author , Halei BenefieldHalei Benefield More articles by this author , Gopa IyerGopa Iyer More articles by this author , David SolitDavid Solit More articles by this author , Matthew MilowskyMatthew Milowsky More articles by this author , William KimWilliam Kim More articles by this author , Matthew NielsenMatthew Nielsen More articles by this author , Sara WobkerSara Wobker More articles by this author , Guido DalbagniGuido Dalbagni More articles by this author , Hikmat Al-AhmadieHikmat Al-Ahmadie More articles by this author , Andrew OlshanAndrew Olshan More articles by this author , Bernard BochnerBernard Bochner More articles by this author , Helena FurbergHelena Furberg More articles by this author , Melissa TroesterMelissa Troester More articles by this author , and Eugene PietzakEugene Pietzak More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002001.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Improved risk stratification and predictive biomarkers of treatment response are needed for non-muscle-invasive bladder cancer (NMIBC). Here we assessed the clinical utility of targeted RNA and DNA molecular profiling in NMIBC. METHODS: Gene expression in NMIBC samples was profiled by NanoString nCounter, a RNA quantification platform, from two independent cohorts (n = 28 & n = 50); targeted panel sequencing was performed in a subgroup (n = 50). Gene signatures were externally validated using a large RNAseq dataset of NMIBC tumors (n = 438). Established molecular subtype classifiers and novel gene expression signatures were assessed for associations with clinicopathologic characteristics, somatic tumor mutations, and treatment outcomes. RESULTS: Molecular subtypes distinguished between low-grade Ta tumors with FGFR3 mutations and overexpression (UROMOL-class 1) and tumors with more aggressive clinicopathologic characteristics (UROMOL-classes 2 and 3), which were significantly enriched with TERT promotor mutations. However, UROMOL subclasses were not associated with recurrence after bacillus Calmette-Guerin (BCG) immunotherapy in two independent cohorts. In contrast, a novel expression signature of an inflamed tumor microenvironment (TME) was associated with improved recurrence-free survival after BCG. Expression of immune checkpoint genes (PD-L1/PD-1/CTLA-4) was associated with an inflamed TME, but not with higher recurrence rates after BCG. FGFR3 mutations and overexpression were both associated with low immune signatures. CONCLUSIONS: Assessment of the immune TME, rather than molecular subtypes, is a promising predictive biomarker of BCG response. Modulating the TME in an immunologically “cold” tumor warrants further investigation. Integrated transcriptomic and exome sequencing should improve treatment selection in NMIBC. Source of Funding: Sidney Kimmel Center for Prostate and Urologic Cancers, Cycle for Survival, Marie-Josée and Henry R. Kravis Center for Molecular Oncology, National Cancer Institute Cancer Center Support Grant P30 CA008748, NCI SPORE in Bladder Cancer P50 CA221745, MSKCC Bladder Cancer SPORE Career Enhancement Award, Bochner-Fleisher Scholars Award, Memorial Sloan Kettering Cancer Center/Weill Medical College of Cornell University Clinical and Translational Science Methodology NIH/NCATS Grant Number UL1-TR002384, NIH/NCI K12 Paul Calabresi Career Development Award for Clinical Oncology (K12 CA184746), Wofchuck Family Young Investigator Award © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e301-e301 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jeffrey Damrauer More articles by this author Kyle Roell More articles by this author Markia Smith More articles by this author Xuezheng Sun More articles by this author Erin Kirk More articles by this author Katherine Hoadley More articles by this author Halei Benefield More articles by this author Gopa Iyer More articles by this author David Solit More articles by this author Matthew Milowsky More articles by this author William Kim More articles by this author Matthew Nielsen More articles by this author Sara Wobker More articles by this author Guido Dalbagni More articles by this author Hikmat Al-Ahmadie More articles by this author Andrew Olshan More articles by this author Bernard Bochner More articles by this author Helena Furberg More articles by this author Melissa Troester More articles by this author Eugene Pietzak More articles by this author Expand All Advertisement Loading ...