Pd41-03 Urinary Comprehensive Genomic Profiling Assists in Non-Invasive Detection and Molecular Staging of Upper Tract Urothelial Carcinoma

You have accessJournal of UrologyBladder Cancer: Upper Tract Transitional Cell Carcinoma III (PD41)1 May 2024PD41-03 URINARY COMPREHENSIVE GENOMIC PROFILING ASSISTS IN NON-INVASIVE DETECTION AND MOLECULAR STAGING OF UPPER TRACT UROTHELIAL CARCINOMA Stephan Brönimann, Maximilian Pallauf, Daniel S. Fischer, Barbara Hamlington, Vincent T. Bicocca, Trevor G. Levin, David J. McConkey, and Nirmish Singla Stephan BrönimannStephan Brönimann , Maximilian PallaufMaximilian Pallauf , Daniel S. FischerDaniel S. Fischer , Barbara HamlingtonBarbara Hamlington , Vincent T. BicoccaVincent T. Bicocca , Trevor G. LevinTrevor G. Levin , David J. McConkeyDavid J. McConkey , and Nirmish SinglaNirmish Singla View All Author Informationhttps://doi.org/10.1097/01.JU.0001008568.76803.f1.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Diagnosing and risk-stratifying upper tract urothelial carcinoma (UTUC) is a clinical challenge. We evaluated the performance of urinary comprehensive genomic profiling (uCGP) in a cohort of patients undergoing treatment for UTUC. METHODS: 67 urine samples were collected from 54 patients prior to surgical extirpation for UTUC. uCGP was performed using the UroAmp assay (Convergent Genomics). The UroAmp disease classification algorithm was previously validated for urothelial carcinoma of the bladder (BLCA) and is tested here along with an exploratory UTUC-adjusted threshold with Lynch syndrome detection. The primary analysis was disease classification compared to pathology. Secondary analyses were grade prediction and cytology classification compared to pathology, mutation comparison by stage, and mutation comparison with de novo pathology-confirmed high grade (HG) BLCA. RESULTS: Grade distribution was 95% high grade (HG) and 5% low grade (LG). Stage distribution was 24% Ta, 18% T1, 12% T2, 27% T3, 4% T4, 10% Tis, 3% Unknown, and 2% T0. uCGP returned conclusive results in all samples and correctly classified 88% of UTUC patients with the validated BLCA algorithm and 91% with the UTUC-adjusted algorithm. The T0 sample was correctly classified as cancer negative. Cytology was performed on 39 samples, returned conclusive results in 26 (67%), and correctly classified 62% of UTUC samples. uCGP correctly classified 100% of atypical cytology results (n=13) with the UTUC-adjusted algorithm. The grade prediction algorithm performed with 100% PPV (95% CI 92-100). Invasive tumors (T1-T4) were enriched in TERT, TP53, PIK3CA, and CREBBP mutations, while superficial tumors (Ta, Tis) were enriched in KMT2D and STAG2 mutations. The strongest predictors of HG BLCA (n=49) versus HG UTUC (n=51) were mutations in ERBB2, TERT, ERBB3, ARID1A, PLEKHS1, and copy number gain in SOX4, which was only observed in HG BLCA (Table 1). CONCLUSIONS: uCGP can identify genomic features associated with UTUC and provide definitive results in cases of atypical cytology. Unique genomic patterns provide insight into tumor grade and origin. This study suggests uCGP can provide diagnostic and prognostic information for the evaluation for UTUC. Source of Funding: Convergent Genomics, South San Francisco, California, USAMaximilian Pallauf gratefully acknowledges the support of the Paracelsus Medical University Research and Innovation Fund (2022-FIRE-004-Pallauf) © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e887 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Stephan Brönimann More articles by this author Maximilian Pallauf More articles by this author Daniel S. Fischer More articles by this author Barbara Hamlington More articles by this author Vincent T. Bicocca More articles by this author Trevor G. Levin More articles by this author David J. McConkey More articles by this author Nirmish Singla More articles by this author Expand All Advertisement PDF downloadLoading ...