Digital Uromonitor® outperforms quantitative polymerase chain reaction Uromonitor and cytology for non-muscle-invasive bladder cancer surveillance: results from the 'External Validation of Uromonitor as a Biomarker for Optimization of NMIBC Management by the Club Urológico Español de Tratamiento Oncológico Group' (EVALUATION-CUETO) study.

Abstract

To compare the performance of a new digital Uromonitor® (dUM; U-Monitor, Porto, Portugal) against the previous quantitative polymerase chain reaction (qPCR) version and cytology in the follow-up of non-muscle-invasive bladder cancer (NMIBC). This retrospective (post hoc) molecular analysis of a prospectively collected multicentre cohort re-analysed stored urine DNA samples from the 'External Validation of Uromonitor as a Biomarker for Optimization of NMIBC Management by the Club Urológico Español de Tratamiento Oncológgico Group' (EVALUATION-CUETO) study (ClinicalTrials.gov identifier: NCT05864599). Samples, previously tested with Uromonitor-version 2, were analysed using dUM (QX200™ Droplet Digital PCR System) for TERT and FGFR3 hotspot mutations. Performance metrics (sensitivity, specificity, positive predictive value [PPV], negative predictive value [NPV], area under the curve [AUC]) for detecting recurrence were calculated against cystoscopy/histology and compared to qPCR and cytology. The study received approval from the Ethical Committee at the University Hospital of Vall d'Hebron (Barcelona). Analysis of 271 samples revealed dUM had superior sensitivity to qPCR (72% vs 36%) and cytology (72% vs 34%), while preserving high specificity (88%) and NPV (93%). The AUC for dUM was 0.80 vs 0.66 for qPCR. Performance was consistent across tumour grades and risk groups. Crucially, combining a positive/suspicious cystoscopy with a positive dUM result significantly increased the PPV to 94% (from 79% for cystoscopy alone). The dUM significantly outperformed its qPCR predecessor and cytology in sensitivity for detecting NMIBC recurrence in a real-world setting, without compromising specificity. Its high NPV supports its potential for reducing unnecessary cystoscopies. Furthermore, its combination with cystoscopy drastically increased the PPV, suggesting a role as an adjunctive tool to improve diagnostic confidence and potentially reduce unnecessary transurethral resections of bladder tumour, pending favourable cost-effectiveness.