Urinary comprehensive genomic profiling predicts urothelial carcinoma recurrence and identifies responders to intravesical therapy.

Intravesical therapy (IVT) is the standard of care to decrease risk of recurrence and progression for high-grade non-muscle-invasive bladder cancer (NMIBC). However, post-IVT recurrence remains common and the ability to risk-stratify patients before or after IVT is limited. In this prospectively designed and accrued cohort study, we examine the utility of urinary comprehensive genomic profiling (uCGP) for predicting recurrence risk following transurethral resection of bladder tumor (TURBT) and evaluating longitudinal IVT response. Urine was collected before and after IVT instillation and uCGP testing was done using the UroAmpTM platform. Baseline uCGP following TURBT identified patients with high (61%) and low (39%) recurrence risk. At 24 months, recurrence-free survival (RFS) was 100% for low-risk and 45% for high-risk patients with a hazard ratio of 9.3. Longitudinal uCGP classified patients as minimal residual disease (MRD) Negative, IVT Responder, or IVT Refractory with 24-month RFS of 100%, 50%, and 32%, respectively. Compared to MRD Negative patients, IVT Refractory patients had a hazard ratio of 10.5. Collectively, uCGP enables noninvasive risk assessment of patients following TURBT and induction IVT. uCGP could inform surveillance cystoscopy schedules and identify high-risk patients in need of additional therapy.

Molecular oncology. 2023 Sep 27 [Epub ahead of print]

Goran Rac, Hiten D Patel, Christopher James, Shalin Desai, Vincent M Caruso, Daniel S Fischer, Peter S Lentz, Ceressa T Ward, Brian C Mazzarella, Kevin G Phillips, Chirag Doshi, Vincent T Bicocca, Trevor G Levin, Alan J Wolfe, Gopal N Gupta

Department of Urology, Loyola University Medical Center, Maywood, IL., Convergent Genomics, Inc., South San Francisco, CA., Department of Microbiology and Immunology, Loyola University Chicago, Maywood, IL.