Improving long-term monitoring in NMIBC: Digital Uromonitor® (dUM) as a complementary tool to cystoscopy for two-year recurrence risk stratification.

OBJECTIVE

Non-muscle-invasive bladder cancer (NMIBC) has a high risk of recurrence and requires intensive long-term surveillance. Existing clinical risk models offer limited prognostic accuracy. Molecular urine-based assays may improve prognostic assessment accuracy of future recurrence. This study evaluated whether Digital Uromonitor® (dUM), detecting TERT and FGFR3 mutations via ddPCR, enhances prognostic assessment of two-year recurrence beyond cystoscopy and cytology in a prospective multicenter cohort.

METHODS

This prospective, multicenter observational study (EVALUATION-CUETO; NCT05864599) enrolled consecutive NMIBC patients from 26 institutions. Eligible participants had an index tumor diagnosed 3 months-2 years before recruitment and completed two years of follow-up with sufficient DNA for dUM analysis. Clinical, pathological, and biomarker variables (cystoscopy, cytology, dUM) were collected. Recurrence rate was defined as events per year and classified as high (R > 0.5) or low (R ≤ 0.5).

RESULTS

Of 201 included patients, 75 (37%) were dUM-positive; TERT promoter mutations accounted for 88% of these cases. dUM showed prognostic value, correctly identifying 59% of recurrences over two years of standardized FU, outperforming cystoscopy alone (42%), with specificity of 74% and NPV of 78%. Combining dUM with cystoscopy increased sensitivity to 71%. Patients negative for both cystoscopy and TERT had the lowest recurrence risk (14%), whereas dual-positive patients exceeded 80%. High baseline recurrence rate consistently increased risk across all biomarker categories.

CONCLUSIONS

dUM provides robust, reproducible prognostic information and significantly improves molecular risk stratification in NMIBC. These findings support its potential integration into risk-adapted surveillance strategies, pending validation in larger populations.