Critical review of biomarkers for the early detection and surveillance of bladder cancer

Increasing interest in the early diagnosis of urothelial carcinoma of the bladder (UCB) has led to a better understanding of bladder carcinogenesis and an explosion of new biomarkers for this disease. Current surveillance protocols after initial diagnosis include serial cystoscopy, which is invasive and expensive, and cytology, which has a low sensitivity and suffers from high variability. To date, the US Food and Drug Administration (FDA) has approved six urine-based biomarkers to complement cystoscopy in the monitoring of UCB patients. In addition, various promising tests are under investigation.In this review, we describe the rationale and address the most recent and relevant findings for the FDA-approved biomarkers (bladder tumor antigen (BTA) test, BTA stat, BTA TRAK, ImmunoCyt, NMP22, and UroVysion) and the most promising investigational biomarkers (urinary UCB test, BLCA-1, BLCA-4, hyaluronic acid, hyaluronidase, Lewis X antigen, microsatellite analysis, Quanticyt, soluble Fas, survivin, telomerase, and cytokeratin 20).Most of the comparative studies have shown that noninvasive biomarkers have equal or higher sensitivity for UCB detection than cytology, even in high-grade cancers. None of these tests, however, meets all of the criteria of an ideal tumor biomarker. For the investigational biomarkers, improved standardization and automation are still required, as well as prospective, large-scale assessment in heterogeneous patient populations. Moreover, despite the use of urine biomarkers in a variety of clinical situations, their role is not well defined at this time.Identifying an optimal marker that would replace, delay, or complement cystoscopy and/or cytology in the monitoring of patients with UCB is still ongoing. Urinary biomarkers may eventually be used to screen patients at high-risk, to help diagnose or even predict disease recurrence, and to decrease the need for invasive procedures.