PD46-03 UTILITY OF URINARY TUMOR DNA DETECTION IN TREATMENT-NAÏVE UTUC

Abstract

You have accessJournal of UrologyCME1 Apr 2023PD46-03 UTILITY OF URINARY TUMOR DNA DETECTION IN TREATMENT-NA&IUML;VE UTUC Heather Huelster, Facundo Davaro, Kyle Rose, Billie Gould, Tiantian Zheng, Prithvi Murthy, Shreyas Naidu, Lucia Camperlengo, Pan Du, Shidong Jia, Aram Vosoughi, and Roger Li Heather HuelsterHeather Huelster More articles by this author , Facundo DavaroFacundo Davaro More articles by this author , Kyle RoseKyle Rose More articles by this author , Billie GouldBillie Gould More articles by this author , Tiantian ZhengTiantian Zheng More articles by this author , Prithvi MurthyPrithvi Murthy More articles by this author , Shreyas NaiduShreyas Naidu More articles by this author , Lucia CamperlengoLucia Camperlengo More articles by this author , Pan DuPan Du More articles by this author , Shidong JiaShidong Jia More articles by this author , Aram VosoughiAram Vosoughi More articles by this author , and Roger LiRoger Li More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003359.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Urine-based molecular biomarkers correlate with tumor variants in urothelial carcinoma of the bladder, showing promise for noninvasive detection of newly diagnosed tumors. However, the utility of next-generation sequencing (NGS) to detect urinary tumor DNA (utDNA) in upper tract urothelial carcinoma (UTUC) remains to be explored. Herein, we prospectively sequenced tumors and utDNA at the time of and serially after radical nephroureterectomy (RNU) to examine the feasibility of using utDNA in detection and surveillance of UTUC. METHODS: Fourteen systemic therapy naïve patients with high-grade, clinically-localized UTUC undergoing RNU were prospectively accrued. Urine was collected preoperatively on the day of surgery and urinary supernatant and cell pellets (UCP) processed for extraction of utDNA. NGS used shallow whole-genome sequencing (WGS) to detect genome-wide copy number changes and a 152-pancancer panel (PredicineCARE) to profile single nucleotide variants, small insertions/deletions, and gene-level copy number changes. Variants with mutation allele frequency ≥0.25% in supernatant, ≥0.3% in UCP, and cancer hotspot variants >0.1% were reported. RESULTS: Prior to RNU, utDNA variants were detected in 11/11 (100%) of urinary supernatants and 9/14 (64%) of UCPs using NGS. The most common alterations detected in the urine were in TP53 (81%), TERT promoter (55%), FGFR3 (55%), and ERBB2 (45%). More tumor variants were detected in urine supernatant than UCP (22.9 vs 2.4, p=0.004). Use of a bespoke tumor-informed approach to adjust MAF thresholds for calling variants increased utDNA detection by a mean 0.5 (range 0-3) variants in urinary supernatant and mean 2.3 (range 0-7) variants in UCP. There was no significant difference in the number of variants detected in urine of patients with UTUC staged as <pT2 compared to ≥pT2 or pN+. CONCLUSIONS: UTUC tumor variants are detectable in the urine of treatment-naïve patients undergoing RNU for UTUC using both a panel-based approach and WGS. utDNA detection and dynamics may present an opportunity for personalized monitoring of UTUC. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1170 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Heather Huelster More articles by this author Facundo Davaro More articles by this author Kyle Rose More articles by this author Billie Gould More articles by this author Tiantian Zheng More articles by this author Prithvi Murthy More articles by this author Shreyas Naidu More articles by this author Lucia Camperlengo More articles by this author Pan Du More articles by this author Shidong Jia More articles by this author Aram Vosoughi More articles by this author Roger Li More articles by this author Expand All Advertisement PDF downloadLoading ...