PD47-01 GENOMIC DETERMINANTS OF NESTED VARIANT UROTHELIAL CARCINOMA

Field: Medicine (Health Sciences)

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology IV (PD47)1 Apr 2020PD47-01 GENOMIC DETERMINANTS OF NESTED VARIANT UROTHELIAL CARCINOMA Timothy Clinton*, Karissa Whiting, Vitor Silva, Qiang Li, Nima Almassi, Aditya Bagrodia, Eugene Pietzak, Guido Dalbagni, Gopa Iyer, Bernard Bochner, Irina Ostrovnaya, Anuradha Gopalan, Yingbei Chen, Samson Fine, Satish Tickoo, Maria Arcila, Victor Reuter, David Solit, and Hikmat Al-Ahmadie Timothy Clinton*Timothy Clinton* More articles by this author , Karissa WhitingKarissa Whiting More articles by this author , Vitor SilvaVitor Silva More articles by this author , Qiang LiQiang Li More articles by this author , Nima AlmassiNima Almassi More articles by this author , Aditya BagrodiaAditya Bagrodia More articles by this author , Eugene PietzakEugene Pietzak More articles by this author , Guido DalbagniGuido Dalbagni More articles by this author , Gopa IyerGopa Iyer More articles by this author , Bernard BochnerBernard Bochner More articles by this author , Irina OstrovnayaIrina Ostrovnaya More articles by this author , Anuradha GopalanAnuradha Gopalan More articles by this author , Yingbei ChenYingbei Chen More articles by this author , Samson FineSamson Fine More articles by this author , Satish TickooSatish Tickoo More articles by this author , Maria ArcilaMaria Arcila More articles by this author , Victor ReuterVictor Reuter More articles by this author , David SolitDavid Solit More articles by this author , and Hikmat Al-AhmadieHikmat Al-Ahmadie More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000934.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Nested variant urothelial carcinoma (NVUC) is a historically aggressive variant of bladder cancer with management reliant on radical cystectomy given unclear effectiveness of chemotherapy. Given the aggressive behavior of NVUC, the identification of pathogenic and potentially targetable genomic alterations could suggest novel treatment paradigms for this rare histologic variant. METHODS: Query of our institutional database identified 81 cases of clinically localized NVUC. Each case was re-reviewed by GU pathologists to confirm the histology. Targeted capture sequencing was performed to define the spectrum of genomic alterations in known and putative cancer genes. Clinical and sequencing data was then compared between the nested variant cases and a prospective cohort of clinically localized high-grade urothelial carcinomas, not otherwise specified (UC NOS). RESULTS: On central re-review, tumors were classified as either classic NVUC (N=53) or high-grade urothelial carcinoma with nested features (N=28). A cohort of UC NOS patients (N=600) was used as a comparator. Median follow-up of the overall cohort was 4.3 years. Classic NVUC was associated with higher risk of cancer specific mortality compared to UC NOS on multivariate analysis (HR 1.76, p=0.04). Tumor mutational burden was lower in classic NVUC tumors versus UC NOS. Evaluation of 136 cancer-associated genes identified differences in mutational frequencies across the 3 cohorts (Table 1) with RhoA and FOXA1 alterations enriched in NVUC. CONCLUSIONS: Patients with NVUC have significantly higher risk of cancer specific mortality than patients with UC NOS. While there was significant overlap between the landscape of genomic alterations in NVUC and UC NOS tumors, NVUC tumors were enriched for RhoA and FOXA1 alterations among others. Source of Funding: This work was supported by the Sidney Kimmel Center for Prostate and Urologic Cancers, the Michael and Zena Wiener for Therapeutics Program in Bladder Cancer, Pin Down Bladder Cancer, Cycle for Survival, the Marie-Josee and Henry R. Kravis Center for Molecular Oncology, NIH/NCATS Grant Number UL1-TR002384, the National Cancer Institute Cancer Center Core Grant Number P30-CA008748 and by SPORE in Bladder Cancer P50-CA221745. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e925-e925 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Timothy Clinton* More articles by this author Karissa Whiting More articles by this author Vitor Silva More articles by this author Qiang Li More articles by this author Nima Almassi More articles by this author Aditya Bagrodia More articles by this author Eugene Pietzak More articles by this author Guido Dalbagni More articles by this author Gopa Iyer More articles by this author Bernard Bochner More articles by this author Irina Ostrovnaya More articles by this author Anuradha Gopalan More articles by this author Yingbei Chen More articles by this author Samson Fine More articles by this author Satish Tickoo More articles by this author Maria Arcila More articles by this author Victor Reuter More articles by this author David Solit More articles by this author Hikmat Al-Ahmadie More articles by this author Expand All Advertisement PDF downloadLoading ...