Urinary biomarkers for bladder cancer diagnosis and NMIBC follow-up: a systematic review

Background: Bladder cancer detection and follow-up is based on cystoscopy and/or cytology, but it remains imperfect and invasive. Current research focuses on diagnostic biomarkers that could improve bladder cancer detection and follow-up by discriminating patients at risk of aggressive cancer who need confirmatory TURBT (Transurethral Resection of Bladder Tumour) from patients at no risk of aggressive cancer who could be spared from useless explorations.

Objective: To perform a systematic review of data on the clinical validity and clinical utility of eleven urinary biomarkers (VisioCyt^®, Xpert^®Bladder, BTA stat^®, BTA TRAK™, NMP22 BC^®, NMP22^® BladderChek^® Test, ImmunoCyt™/uCyt1+™, UroVysion Bladder Cancer Kit^®, Cxbladder, ADXBLADDER, Urodiag^®) for bladder cancer diagnosis and for non-muscle invasive bladder cancer (NMIBC) follow-up.

Methods: All available studies on the 11 biomarkers published between May 2010 and March 2021 and present in MEDLINE^® were reviewed. The main endpoints were clinical performance for bladder cancer detection, recurrence or progression during NMIBC monitoring, and additional value compared to cytology and/or cystoscopy.

Results: Most studies on urinary biomarkers had a prospective design and high level of evidence. However, their results should be interpreted with caution given the heterogeneity among studies. Most of the biomarkers under study displayed higher detection sensitivity compared with cytology, but lower specificity. Some biomarkers may have clinical utility for NMIBC surveillance in patients with negative or equivocal cystoscopy or negative or atypical urinary cytology findings, and also for recurrence prediction.

Conclusion: Urinary biomarkers might have a complementary place in bladder cancer diagnosis and NMIBC surveillance. However, their clinical benefit remains to be confirmed.