Biology and performance of pre- and post-pembrolizumab (pembro) vesical imaging-reporting and data system (VI-RADS) to predict the pathological response in muscle-invasive urothelial bladder cancer (MIBC): Full data analysis from a clinical trials pipeline.

You have accessJournal of UrologyCME1 Apr 2023LBA03-12 BIOLOGY AND PERFORMANCE OF PRE- AND POST-PEMBROLIZUMAB (PEMBRO) VESICAL IMAGING-REPORTING AND DATA SYSTEM (VI-RADS) TO PREDICT THE PATHOLOGICAL RESPONSE IN MUSCLE-INVASIVE UROTHELIAL BLADDER CANCER (MIBC): FULL DATA ANALYSIS FROM A CLINICAL TRIALS PIPELINE Andrea Necchi, Giuseppe Basile, Ewan Gibb, Giuseppina Calareso, Tiago Padua, Damiano Patanè, Emanuele Crupi, Chiara Mercinelli, Andrea Del Prete, Patrizia Giannatempo, Marco Moschini, Jeffrey Ross, Alberto Briganti, Francesco Montorsi, Antonella Messina, Francesco De Cobelli, and Giorgio Brembilla Andrea NecchiAndrea Necchi More articles by this author , Giuseppe BasileGiuseppe Basile More articles by this author , Ewan GibbEwan Gibb More articles by this author , Giuseppina CalaresoGiuseppina Calareso More articles by this author , Tiago PaduaTiago Padua More articles by this author , Damiano PatanèDamiano Patanè More articles by this author , Emanuele CrupiEmanuele Crupi More articles by this author , Chiara MercinelliChiara Mercinelli More articles by this author , Andrea Del PreteAndrea Del Prete More articles by this author , Patrizia GiannatempoPatrizia Giannatempo More articles by this author , Marco MoschiniMarco Moschini More articles by this author , Jeffrey RossJeffrey Ross More articles by this author , Alberto BrigantiAlberto Briganti More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , Antonella MessinaAntonella Messina More articles by this author , Francesco De CobelliFrancesco De Cobelli More articles by this author , and Giorgio BrembillaGiorgio Brembilla More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003426.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The VI-RADS is a standardized reporting system that uses multiparametric magnetic resonance imaging (mpMRI) parameters to predict the probability of MIBC. It has been also used in studies using standard-of-care perioperative or bladder-sparing therapies. No studies have analyzed the performance of VI-RADS to predict the pT0 or pT ≤1 response post-immunotherapy (IO) in MIBC. METHODS: In PURE-01 study patients (pts) were staged with mpMRI before and after treatment (3 cycles of pembro) prior to radical cystectomy (RC). All mpMRI scans were centrally reviewed. Logistic regression models analyzed pre- and post-pembro VI-RADS against pT ≤1 (primary endpoint) and pT0 (secondary endpoint). VI-RADS scores were dichotomized between 0-3 (0=no evidence of disease) and 4-5. Covariates included cT-stage, age, gender, PD-L1 combined positive score (CPS) and tumor mutational burden (TMB). Model performance was also tested in the ongoing NureCombo (nivolumab+nab-paclitaxel; NCT04876313) and SURE-01 (sacituzumab govitecan; NCT05226117) studies. Transcriptome-wide expression profiling was matched with VI-RADS scores. RESULTS: In PURE-01, 115 pts had centrally-reviewed MRI scans (N=230 mpMRI), treated between 02/17 and 08/18. In total, 32 (27.8%) had pure/predominant non-urothelial carcinoma (UC) histology, 54 (47%) had a cT3-4N0 MIBC. Pre-pembro: 21 pts (18.3%) had no measurable disease (VI-RADS=0), 37 (32.2%) a VI-RADS 1-3 score, and 57 (49.5%) had a VI-RADS 4-5 score. 20 pts (17.4%) had a downstage from VI-RADS 4-5 to VIRADS 0-3 post-pembro. Pre-pembro VIRADS 4-5 were associated with higher angiogenesis and epithelial-mesenchymal transition (EMT) activity vs VI-RADS 0-3 (p=0.011 and 0.033).Both pre-pembro and post-pembro VI-RADS 0-3 scores were the only significant covariates against pT ≤1 endpoint on multivariable analyses (MVA): the strongest effect was seen with post-pembro VI-RADS 0-3 against pT ≤1 response (OR: 23.4, 95% CI: 7-95.3, p<0.0001). The AUC of this model was 0.90. Model-based decisions were supported in the range of threshold probabilities of 10-80%. Post-pembro VI-RADS 4-5 were characterized by higher stromal signature scores vs VI-RADS 0-3.When post-therapy VI-RADS were tested in evaluable pts from the combined NureCombo+SURE-01 cohort (N=17; 34 total mpMRI scans): 90% of post-VI-RADS 0-3 revealed a pT ≤1 stage at radical cystectomy. CONCLUSIONS: VI-RADS scores mirrored distinct biological features in MIBC, recapitulating tissue biomarkers of IO response. VI-RADS scores post-IO revealed a strong association with pathological downstaging and represented a robust feature based on which selecting pts for bladder-sparing strategies. Results seemed to be also applicable to other novel neoadjuvant therapies beyond IO monotherapy. Source of Funding: AIRC (Associazione Italiana per la Ricerca sul Cancro).Merck Inc.Gilead Biosciences Inc.Bristol-Myers Squibb (BMS) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1196-e1197 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Andrea Necchi More articles by this author Giuseppe Basile More articles by this author Ewan Gibb More articles by this author Giuseppina Calareso More articles by this author Tiago Padua More articles by this author Damiano Patanè More articles by this author Emanuele Crupi More articles by this author Chiara Mercinelli More articles by this author Andrea Del Prete More articles by this author Patrizia Giannatempo More articles by this author Marco Moschini More articles by this author Jeffrey Ross More articles by this author Alberto Briganti More articles by this author Francesco Montorsi More articles by this author Antonella Messina More articles by this author Francesco De Cobelli More articles by this author Giorgio Brembilla More articles by this author Expand All Advertisement PDF downloadLoading ...