Pd14-05 the Stroma-Rich Consensus Bladder Cancer Subtype Correlates With Improved Prognosis After Neoadjuvant Immunotherapy and Radical Cystectomy

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology II (PD14)1 May 2024PD14-05 THE STROMA-RICH CONSENSUS BLADDER CANCER SUBTYPE CORRELATES WITH IMPROVED PROGNOSIS AFTER NEOADJUVANT IMMUNOTHERAPY AND RADICAL CYSTECTOMY Joep J. de Jong, Moritz Reike, Bernadett Szabados, Alex Hakansson, Andrea Necchi, Tom Powles, and Ewan Gibb Joep J. de JongJoep J. de Jong , Moritz ReikeMoritz Reike , Bernadett SzabadosBernadett Szabados , Alex HakanssonAlex Hakansson , Andrea NecchiAndrea Necchi , Tom PowlesTom Powles , and Ewan GibbEwan Gibb View All Author Informationhttps://doi.org/10.1097/01.JU.0001009472.76470.8c.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: In patients with muscle-invasive bladder cancer (MIBC), molecular alterations that predict benefit from neoadjuvant immunotherapy remain largely unstudied. This study aims to evaluate the ability of molecular signatures to predict outcomes after neoadjuvant atezolizumab plus radical cystectomy (RC) and to explore the biology of atezolizumab-resistant tumors. METHODS: RNA-seq data from TURBT samples from the ABACUS trial were available for gene expression analyses from N=84 patients treated with neoadjuvant atezolizumab of whom N=50 had matched residual bladder cancer RC samples (post-atezolizumab; PMID 31686036). RC samples were also profiled for N=14 patients that showed a complete pathologic response. Pre- and post-atezolizumab tumor gene expression (RNA-seq) data was classified into molecular subtypes using the consensus subtyping model. Unsupervised consensus clustering (CC) was performed to categorize the RC samples and each cluster was characterized using gene expression signatures. The PURE-01 RC cohort (N=26 post-pembrolizumab; PMID 34301456), was also characterized using the consensus model. The Kaplan-Meier method was used to estimate differences in patient outcomes. RESULTS: Unsupervised CC revealed three distinct post-atezolizumab clusters (scar-like, luminal & basal). The scar-like cluster was present in 38% (19/50) of the post-atezolizumab tumors and expressed genes associated with wound healing/scarring. Survival analyses for different classifications revealed 11 out of 12 residual stroma-rich tumors by the consensus subtyping classifier were among the scar-like cluster at RC, showing improved survival - even comparable with complete responders at RC. The stroma-rich subtype showed favorable prognosis with only one relapse event (median follow-up 13.1 months). In the PURE-01 RC cohort, 12 out of 13 cases from the scar-like cluster (also reported for pembrolizumab-treated tumors) were classified as stroma-rich by the consensus subtype, representing a subgroup with improved recurrence-free survival outcomes. CONCLUSIONS: This study expands our understanding of the biology of atezolizumab resistant MIBC and contributes to the framework for defining molecular subtypes at RC. These results further support the hypothesis that residual bladder cancer with a scar-like / stroma-rich profile may predict improved patient prognosis after neoadjuvant immunotherapy treatment and RC. Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e355 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Joep J. de Jong More articles by this author Moritz Reike More articles by this author Bernadett Szabados More articles by this author Alex Hakansson More articles by this author Andrea Necchi More articles by this author Tom Powles More articles by this author Ewan Gibb More articles by this author Expand All Advertisement PDF downloadLoading ...