MP56-03 A COMPLIMENTARY ANALYSIS OF PLASMACYTOID UROTHELIAL CARCINOMA OF THE BLADDER: GENOMIC LANDSCAPE INDEPENDENT OF SOMATIC CDH1 MUTATIONS AND REAL-WORLD CLINICAL OUTCOME STUDY

You have accessJournal of UrologyCME1 Apr 2023MP56-03 A COMPLIMENTARY ANALYSIS OF PLASMACYTOID UROTHELIAL CARCINOMA OF THE BLADDER: GENOMIC LANDSCAPE INDEPENDENT OF SOMATIC CDH1 MUTATIONS AND REAL-WORLD CLINICAL OUTCOME STUDY Kyle Rose, Andrea Necchi, Facundo Davaro, Elizabeth Davaro, Heather Huelster, Joseph Jacob, Grennady Bratslavsky, Dean Pavlick, Douglas Lin, Natalie Danzinger, Petros Grivas, Hikmat Al-Ahmadie, Vamsi Parimi, Philippe Spiess, Bishoy Faltas, Jeffrey Ross, and Roger Li Kyle RoseKyle Rose More articles by this author , Andrea NecchiAndrea Necchi More articles by this author , Facundo DavaroFacundo Davaro More articles by this author , Elizabeth DavaroElizabeth Davaro More articles by this author , Heather HuelsterHeather Huelster More articles by this author , Joseph JacobJoseph Jacob More articles by this author , Grennady BratslavskyGrennady Bratslavsky More articles by this author , Dean PavlickDean Pavlick More articles by this author , Douglas LinDouglas Lin More articles by this author , Natalie DanzingerNatalie Danzinger More articles by this author , Petros GrivasPetros Grivas More articles by this author , Hikmat Al-AhmadieHikmat Al-Ahmadie More articles by this author , Vamsi ParimiVamsi Parimi More articles by this author , Philippe SpiessPhilippe Spiess More articles by this author , Bishoy FaltasBishoy Faltas More articles by this author , Jeffrey RossJeffrey Ross More articles by this author , and Roger LiRoger Li More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003309.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Plasmacytoid urothelial carcinomas of the bladder (PUC) represent an aggressive malignancy with somatic CDH1 mutations, poor survival, and few systemic therapy options. We aimed to analyze the genomic landscape of urothelial carcinomas stratified by CDH1 status and PUC histology, while utilizing real-world clinical outcome data. METHODS: 7,903 clinically advanced patients with UCB underwent hybrid capture based comprehensive genomic profiling (CGP) to evaluate all classes of genomic alterations (GAs) as well as microsatellite instability (MSI), tumor mutational burden (TMB), and genomic loss of heterozygosity (gLOH, high≥16%). Plasmacytoid histology was confirmed by pathologic evaluation. GAs were compared by plasmacytoid histology and CDH1-mutated (CDH1-M) vs. wild-type (WT). The Flatiron Heath-Foundation Medicine Urothelial Clinico-Genomic Database (FH-FMI CGDB) was used to characterize overall survival (OS) and progression-free survival (PFS) in CDH1-M vs. WT, stratified by systemic therapy administered. RESULTS: CDH1 mutations were identified in 158 patients, who demonstrated a higher frequency MSI-high status (2.7% vs. 0.8%, p<0.01), mean TMB (14.8 vs. 9.9%, p<0.01), but lower gLOH (6.8% vs. 20.3%, p<0.01). PUC was identified on pathologic analysis in 103 (65%) patients with CDH1 mutations. Table 1 demonstrates the frequency of GAs between these three groups. There were no differences in genes associated with DNA damage response. In the non-PUC cohort, GAs on chromosome 9p21 were increasingly mutated. From the FH-FMI CGDB, 22 patients (3.7%) featured CDH1 mutations, and shared similar demographics to CDH1-WT. These patients demonstrated worse OS (OS 3.3 vs. 9.5 months, p=0.03) and PFS (2.8 vs 3.5 months; p=0.09) when treated with immune checkpoint inhibitors, but no difference following chemotherapy. CONCLUSIONS: CDH1 mutations are not exclusive to PUC, which possesses a distinct genomic profile and natural history. Real-world clinical outcomes support that CDH1 mutations predict resistance to immune checkpoint inhibition, but not chemotherapy. Taken together, these results further support genomic profiling of advanced bladder tumors and treatment individualization based on genomic signatures. Source of Funding: NA © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e774 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kyle Rose More articles by this author Andrea Necchi More articles by this author Facundo Davaro More articles by this author Elizabeth Davaro More articles by this author Heather Huelster More articles by this author Joseph Jacob More articles by this author Grennady Bratslavsky More articles by this author Dean Pavlick More articles by this author Douglas Lin More articles by this author Natalie Danzinger More articles by this author Petros Grivas More articles by this author Hikmat Al-Ahmadie More articles by this author Vamsi Parimi More articles by this author Philippe Spiess More articles by this author Bishoy Faltas More articles by this author Jeffrey Ross More articles by this author Roger Li More articles by this author Expand All Advertisement PDF downloadLoading ...