Urine Tumor DNA Testing Identifies Recurrence and Monitors Therapy Response in Patients with High-Risk Non-Muscle-Invasive Bladder Cancer Receiving Intravesical Bacillus Calmette-Guérin.

Abstract

PURPOSE: Intravesical Bacillus Calmette-Guerin (BCG) is the preferred treatment for high-risk non-muscle-invasive bladder cancer (NMIBC). However, many patients recur within the first year despite optimal therapy. Urine tumor DNA (utDNA) offers promise in stratifying therapy response to identify patients who may benefit from treatment intensification or de-escalation. Our study aimed to validate utDNA testing in a multicenter cohort of patients receiving BCG. METHODS: Pretreatment/post-treatment urine from patients undergoing BCG for NMIBC was analyzed by UroAmp. utDNA disease classification (positive/negative) and genomic disease burden (GDB) were determined according to previously established tumor-naïve algorithms. Kaplan-Meier recurrence-free survival (RFS) analyses were conducted to compare groups and Cox proportional hazards assessed. RESULTS: Forty percent (23/57) of patients were utDNA positive before the first BCG treatment. utDNA positive patients had a 12-month RFS of 61% compared with 85% for negative patients (HR = 3.2, P = .04). Post-BCG, 19% (8/43) of clinically negative patients were utDNA positive. These patients had a 12-month RFS of 25% compared with 91% for negative patients (HR = 10.0, P < .001). Among future recurrences, 33% were identified by utDNA when clinical surveillance was negative, providing a median lead time (time between molecular detection and clinical diagnosis) of 4.1 months over standard of care. 67% of lead time cases went on to radical cystectomy and 33% progressed to muscle-invasive disease. CONCLUSIONS: utDNA analysis reliably stratifies risk of recurrence in patients receiving BCG and shows promise to identify early recurrence enabling personalized treatment.