Introduction Bladder cancer (BC) remains the most common malignancy of the urinary tract, with non-muscle invasive BC (NMIBC) representing the vast majority of bladder cancer patients. The current standard of care (SOC)follow-up in NMIBC patients demands an intensive scheduleand requires costly and burdensome methods, driving the development alternative, non-invasive, cost-effective methods that may complement or serve as alternatives to cystoscopy and cytology. Uromonitor is a urine biomarker test that detects hotspot mutations in three genes (TERT, FGFR3, and KRAS) for the evaluation of disease recurrence. The aim of the current study was to assess its performance comparing it to the current SOC methods.

Materials and Methods A total of 528 NMIBC surveillances from 490 individual patients were enrolled from December 2021 to June 2023. All subjects underwent SOC methods and provided a urine sample before undergoing cystoscopy for Uromonitor analysis. Sensibility, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for recurrence and compared to the gold-standard trans-urethral resection (TURBT) pathology.

Results Uromonitor displayed a positive predictive value (PPV) of 93,18% and a negative predictive value (NPV) of 98,76%. Cystoscopy showed a total of 22 (31,88%) false positives not confirmed by TURBT, while there were only 3 urine positive tests where no suspected lesions were found in cystoscopy. Sensitivity, specificity and NPV values for Uromonitor remained high across all NIBC grades and stages. Uromonitor missed detecting mutations in urine of 6 cases which, nonetheless were all detected in TURBT tissue, confirming extensive coverage of the biomarkers and highlighting need for rigorous collection and filtration procedure for adequate sampling of mutations in urine.

Conclusion In the present trial, we confirmed that the Uromonitor biomarker test represents a reliable tool in the detection of NMIBC recurrence in patients undergoing routine surveillance, regardless of stage and grade. It offers either an alternative or a complement to the current SOC methods, providing rapid results and a non-invasive option, potentially improving patients quality of life and helping reduce the burden of NMIBC follow-up. To our knowledge, this is the largest single-center study assessing Uromonitor performance and thus validating its usefulness in clinical practice.

The authors have declared no competing interest.

This study did not receive any funding

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Written informed consent was obtained from the patients participating in the study. Procedures were previously approved by Ethical Review Committee in University Hospital Centre of São João.

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All data produced in the present study are available upon reasonable request to the authors