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

PURPOSE: Intravesical bacillus Calmette-Guérin (BCG) is the preferred treatment for high-risk nonmuscle-invasive bladder cancer. 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.

MATERIALS AND

METHODS

Pretreatment/posttreatment urine from patients undergoing BCG for nonmuscle-invasive bladder cancer was analyzed by utDNA testing (UroAmp). utDNA disease classification (positive/negative) and genomic disease burden 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 utDNA-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. Sixty-seven percent 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.