Mp71-19 Ultrasensitive Urinary Liquid Biopsy Analysis for BCG Response Assessment in High-Risk Non-Muscle Invasive Bladder Cancer

You have accessJournal of UrologyBladder Cancer: Non-invasive IV (MP71)1 May 2024MP71-19 ULTRASENSITIVE URINARY LIQUID BIOPSY ANALYSIS FOR BCG RESPONSE ASSESSMENT IN HIGH-RISK NON-MUSCLE INVASIVE BLADDER CANCER William Y. Shi, Kevin J. Liu, Mohammad S. Esfahani, Joseph G. Schroers-Martin, Monica Nesselbush, Simon B. Chen, Stefan K. Alig, Patrick Mullane, Kathleen E. Mach, Ludimila Trabanino, Timothy J. Lee, Ihna Yoo, Vinh La, Gabriela Rodriguez, Zachary Kornberg, Eugene Shkolyar, Harcharan Gill, Alan Thong, Jay B. Shah, Kris Prado, Eila C. Skinner, Ash A. Alizadeh, Joseph C. Liao, and Maximilian Diehn William Y. ShiWilliam Y. Shi , Kevin J. LiuKevin J. Liu , Mohammad S. EsfahaniMohammad S. Esfahani , Joseph G. Schroers-MartinJoseph G. Schroers-Martin , Monica NesselbushMonica Nesselbush , Simon B. ChenSimon B. Chen , Stefan K. AligStefan K. Alig , Patrick MullanePatrick Mullane , Kathleen E. MachKathleen E. Mach , Ludimila TrabaninoLudimila Trabanino , Timothy J. LeeTimothy J. Lee , Ihna YooIhna Yoo , Vinh LaVinh La , Gabriela RodriguezGabriela Rodriguez , Zachary KornbergZachary Kornberg , Eugene ShkolyarEugene Shkolyar , Harcharan GillHarcharan Gill , Alan ThongAlan Thong , Jay B. ShahJay B. Shah , Kris PradoKris Prado , Eila C. SkinnerEila C. Skinner , Ash A. AlizadehAsh A. Alizadeh , Joseph C. LiaoJoseph C. Liao , and Maximilian DiehnMaximilian Diehn View All Author Informationhttps://doi.org/10.1097/01.JU.0001009548.76580.ba.19AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Standard-of-care treatment for high-risk non-muscle invasive bladder cancer (NMIBC) is transurethral resection of bladder tumor (TURBT) followed by adjuvant Bacillus Calmette-Guérin (BCG), yet monitoring response is challenging. Noninvasive biomarkers such as urinary tumor DNA (utDNA) could improve assessment of NMIBC recurrence after BCG. We have developed a liquid biopsy assay called urinary Cancer Personalized Profiling by Deep Sequencing (uCAPP-Seq) which has a limit of detection of∼1 part per 10,000 (0.01%). Here, we investigated if uCAPP-Seq utDNA detection can identify responses to BCG in NMIBC. METHODS: We applied tumor-informed uCAPP-Seq to 120 urine specimens from 45 prospectively enrolled high-risk NMIBC patients undergoing BCG induction. GU pathologists annotated tumor and adjacent normal tissue, and DNA was extracted from 1 mm biopsy cores from FFPE blocks. Urine samples were collected prior to TURBT (n=30) and BCG induction (n=45), and at first follow-up after BCG (n=45). The primary endpoint was high-grade recurrence-free survival (HGRFS). RESULTS: uCAPP-Seq analysis identified three major categories of utDNA molecular responses to BCG immunotherapy: 1) utDNA complete response to TURBT (51%; n=23/45 patients), 2) utDNA response to BCG (22%; n=10/45), and 3) no utDNA response (27%; n=12/45) (Fig 1A). Levels of utDNA following BCG were significantly higher in patients with high-grade recurrence (p<0.0001) (Fig 1B). On Kaplan-Meier analysis, patients with persistent utDNA had significantly worse HGRFS compared to patients with responses to TURBT (HR 5.13, 95% CI 1.7-16.5, p=0.0005), and patients with responses to BCG (HR 13.25, 95% CI 4.0-43.7, p=0.0023) (Fig 1C). In patients with utDNA response to BCG, only 10% (n=1/10 patients) experienced high-grade recurrence (Fig 1D). CONCLUSIONS: Detection of utDNA via uCAPP-Seq identifies three types of molecular responses to TURBT and BCG in NMIBC. Molecular response to TURBT and BCG were strongly associated with freedom from high-grade recurrence. About half of patients had complete molecular responses to TURBT, suggesting a significant subset may have been cured by surgery alone. Liquid biopsy detection of utDNA is therefore a promising biomarker for developing personalized treatment strategies for NMIBC. Download PPT Source of Funding: This work is supported by the National Institutes of Health/National Cancer Institute (1R01CA244526) © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e1169 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information William Y. Shi More articles by this author Kevin J. Liu More articles by this author Mohammad S. Esfahani More articles by this author Joseph G. Schroers-Martin More articles by this author Monica Nesselbush More articles by this author Simon B. Chen More articles by this author Stefan K. Alig More articles by this author Patrick Mullane More articles by this author Kathleen E. Mach More articles by this author Ludimila Trabanino More articles by this author Timothy J. Lee More articles by this author Ihna Yoo More articles by this author Vinh La More articles by this author Gabriela Rodriguez More articles by this author Zachary Kornberg More articles by this author Eugene Shkolyar More articles by this author Harcharan Gill More articles by this author Alan Thong More articles by this author Jay B. Shah More articles by this author Kris Prado More articles by this author Eila C. Skinner More articles by this author Ash A. Alizadeh More articles by this author Joseph C. Liao More articles by this author Maximilian Diehn More articles by this author Expand All Advertisement PDF downloadLoading ...