Use of the Xpert Bladder Cancer Monitor Urinary Biomarker Test for Guiding Cystoscopy in High-grade Non–muscle-invasive Bladder Cancer: Results from the Randomized Controlled DaBlaCa-15 Trial

Urinary biomarker tests have long been suggested as a noninvasive alternative to current cystoscopy-based follow-up of high-grade non-muscle-invasive bladder cancer (NMIBC) to reduce both morbidity and costs. However, the clinical impact of urinary biomarker tests remains uncertain owing to a lack of randomized trials. In this randomized noninferiority trial, we evaluated the impact of alternating a urinary biomarker test (Xpert Bladder Cancer Monitor, XBCM) with cystoscopy in the intervention arm as a method for reducing the number of cystoscopies during follow-up of patients with high-grade NMIBC. Patients in the control arm underwent cystoscopy at all follow-up visits. The primary outcome was comparison of the risk of recurrence-free survival in terms of high-grade NMIBC, muscle-invasive bladder cancer, or metastatic urothelial carcinoma between the study arms. In total, 43 high-grade recurrences were detected, 22 in the intervention arm and 21 in the control arm. The risk difference for high-grade recurrence between the study arms was 0.08% (95% confidence interval -7.2% to 7.4%). Two pTa high-grade recurrences were missed by the XBCM test. The number of cystoscopies performed was 1029 cystoscopies in the control arm and 445 in the intervention arm. An anticipatory positive effect was observed, with XBCM positivity observed before recurrences were visible on cystoscopy. The findings are limited by a lower-than-expected rate of recurrence in both study arms. Alternating cystoscopy with XBCM reduced the number of follow-up cystoscopies for high-grade NMIBC without affecting detection of any recurrence. The long-term oncological safety of this strategy needs to be validated over longer follow-up.