Potential of Urinary Mutation and Methylation Biomarkers in Selecting Candidates for Repeat Transurethral Resection of Bladder Tumor in Non-muscle-invasive Bladder Cancer: A Prospective Multicenter Study.

Background and objective: The necessity of repeat transurethral resection of bladder tumor (re-TURBT) in patients with non-muscle-invasive bladder cancer (NMIBC) remains a matter of debate. The role of liquid biopsy in predicting residual tumor status and selecting patients who can be spared re-TURBT is still undefined. The aim of our study was to assess the efficacy of the urinary OncoUrine assay for mutation and methylation markers in determining the necessity for re-TURBT in NMIBC. Methods: We prospectively recruited patients with NMIBC who were candidates for re-TURBT. Urine samples for OncoUrine testing and exfoliated cytology analysis were collected after initial TURBT, followed by re-TURBT. Key findings and limitations: Among 151 patients with NMIBC, 48 (32%) had residual tumor at re-TURBT, and 87 (58%) had detrusor muscle (DM) in their initial TURBT specimen. The OncoUrine test showed sensitivity of 77%, specificity of 78%, positive predictive value of 62%, and negative predictive value (NPV) of 88% for residual tumor, while exfoliated cytology showed corresponding values of 20%, 96%, 69%, and 72%. Stratified analyses revealed higher OncoUrine accuracy in predicting disease-free status in intermediate-risk NMIBC (NPV 98%) and in high-risk NMIBC cases with DM in the initial TURBT specimen (NPV 92%). At 18-mo follow-up for 131 patients, 20 had experienced tumor recurrence, for which OncoUrine positivity was the only independent factor predictive for the risk of recurrence (hazard ratio 3.67, 95% confidence interval 1.49-9.00; Conclusions and clinical implications: The OncoUrine test may identify patients who can avoid unnecessary re-TURBT, especially for intermediate-risk NMIBC cases and high-risk NMIBC cases with DM in the initial TURBT specimen. Conversely, patients with a positive OncoUrine result are at higher risk of recurrence and should undergo re-TURBT. Patient summary: OncoUrine is a urine test that can help in identifying patients with non-muscle-invasive bladder cancer who may be able to avoid unnecessary repeat resection of the bladder.