Noninvasive Early Detection and Recurrence Monitoring for Non‐Muscle‐Invasive Bladder Cancer via Urine Tumor DNA: A Prospective Clinical Study

TL;DR

A urine-based test called utLIFE-UC accurately detects non-muscle invasive bladder cancer and predicts recurrence, potentially reducing the need for invasive procedures.

Contribution

The study presents the first prospective, longitudinal analysis of urinary tumor DNA for non-muscle invasive bladder cancer surveillance.

Findings

utLIFE-UC detected NMIBC with 90.5% sensitivity and accurately identified residual tumor after surgery.

Positive test results predicted future relapse with a median lead time of 73.5 days.

Sustained negative results indicated recurrence-free status, improving risk stratification.

Abstract

Conventional approaches for the detection and surveillance of non‐muscle invasive bladder cancer (NMIBC) remain invasive, burdensome, and costly. The utLIFE‐UC assay, designed to identify mutations and large copy number variations in urine, has demonstrated high accuracy in detecting urothelial carcinoma. Here, we assessed its efficacy in early detection of NMIBC, identifying minimal residual disease, and monitoring recurrence. Among 108 consecutive NMIBC patients evaluated, utLIFE‐UC exhibited a sensitivity of 90.5% in diagnosing NMIBC, with comparable performance in detecting both de novo and recurrent NMIBC. For patients undergoing repeat transurethral resection of bladder tumor (Re‐TURBT), the assay accurately identified all cases with residual tumor, achieving a 100% negative predictive value. Positive postoperative utLIFE‐UC results before the first follow‐up cystoscopy predicted a higher risk of future relapse. A positive test result at any time following TURBT was correlated with poorer recurrence‐free survival, whereas sustained negative test results indicated recurrence‐free status. Moreover, utLIFE‐UC could predict recurrence with a median lead time of 73.5 days prior to clinical confirmation. As the first prospective, longitudinal analysis of urinary tumor DNA in NMIBC, this study highlights the potential of utLIFE‐UC to enable earlier recurrence detection and improve risk stratification, potentially obviating unnecessary Re‐TURBT and surveillance cystoscopies.

In NMIBC surveillance, positive postoperative utLIFE‐UC results before initial follow‐up cystoscopy were significantly associated with increased relapse risk. Longitudinal analysis showed that positive utLIFE‐UC results at any time after TURBT correlated with worse recurrence‐free survival, while sustained negative results predicted recurrence‐free status. This approach offers potential to substantially reduce dependence on cystoscopy, thereby revolutionizing NMIBC management and improving patient outcomes.

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