Pd48-03 Detecting Residual Tumor With Cell-Free Urinary Tumor Dna in High-Risk Non-Muscle Invasive Bladder Cancer Patients

You have accessJournal of UrologyBladder Cancer: Non-invasive III (PD48)1 May 2024PD48-03 DETECTING RESIDUAL TUMOR WITH CELL-FREE URINARY TUMOR DNA IN HIGH-RISK NON-MUSCLE INVASIVE BLADDER CANCER PATIENTS Joshua Linscott, Hiro Miyagi, Billie Gould, Prithvi Murthy, Pan Du, Shidong Jia, and Roger Li Joshua LinscottJoshua Linscott , Hiro MiyagiHiro Miyagi , Billie GouldBillie Gould , Prithvi MurthyPrithvi Murthy , Pan DuPan Du , Shidong JiaShidong Jia , and Roger LiRoger Li View All Author Informationhttps://doi.org/10.1097/01.JU.0001008712.53259.7d.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Cell-free urinary tumor DNA (utDNA) harbors detectable genomic alterations that are concordant with bladder tumors and provide a promising biomarker for altering clinical practice. We have prospectively demonstrated that utDNA mutations detect minimal residual disease (MRD) at the time of standard-of-care repeat transurethral resection of bladder tumors (rTURBT) in non-muscle invasive bladder cancer (NMIBC). METHODS: High-risk NMIBC patients were enrolled prior to rTURBT. PredicineWES+™ whole exome sequencing with boosted 600+ oncogene coverage was performed on index TURBT (iTURBT) tissue and/or rTURBT for 34 patients. Urine samples were collected immediately prior to rTURBT (preUR). Low-pass WGS (PredicineSCORE) and PredicineBEACON™ personalized ultra-deep sequencing MRD probes designed from somatic variants from iTURBT (and rTURBT if needed) were used to detect utDNA. MRD probes leverage up to 60 patient-specific mutations and a fixed core hotspot 500 gene panel. Copy number burden (CNB) estimated from LP-WGS, and utDNA tumor fraction (tf) estimated from personalized variant frequencies were evaluated as indicators of MRD. RESULTS: Residual disease was detected pathologically at rTURBT for 22/34 pts (65%) with preUR tf and CNB accurately detecting residual disease, both having 85% sensitivity at 92% specificity. Urinary tf >=2.2% and CNB score >= 5.6 provided the best thresholds for disease prediction, each with an overall AUC of 0.91. Median urinary tf was 3.5% for patients with disease at rTURBT vs. <0.05% (undetectable) for disease-free patients (p<0.001). CONCLUSIONS: Urinary tumor DNA holds promise for detecting MRD prior to rTURBT. Tissue informed probes with ultra-deep sequencing improve detection of MRD where other biomarkers have fallen short. CNB independently performed excellently in detecting residual disease and combining tf with CNB may further optimize test performance. Larger cohorts and long-term follow up will inform trials aiming to change clinical surveillance protocols for NMIBC. Download PPTDownload PPT Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e988 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Joshua Linscott More articles by this author Hiro Miyagi More articles by this author Billie Gould More articles by this author Prithvi Murthy More articles by this author Pan Du More articles by this author Shidong Jia More articles by this author Roger Li More articles by this author Expand All Advertisement PDF downloadLoading ...