Bladder cancer has a very high frequency of recurrence and therefore requires 
lifelong surveillance, traditionally consisting of serial cystoscopy and 
cytology. These tests are both invasive and expensive, with considerable 
inter-user and inter-institutional variability. In addition, the sensitivity of 
cytology in detecting low-grade tumors is low. Therefore, there has been active 
investigation into urinary biomarkers that can either supplement or supplant 
these tests. At this point there are only six urine-based tests that are 
FDA-approved in bladder cancer surveillance, but a wide variety of other 
biomarkers are being studied. In this review, we examine the natural history of 
bladder cancer as well as the rationale and performance of an ideal urinary 
biomarker. The authors describe the FDA-approved biomarkers such as Bladder 
Tumor Antigen, ImmunoCyt, Nuclear Matrix Protein-22, and Fluorescent In Situ 
Hybridization, as well as the most promising investigational tests (i.e., 
Urinary bladder cancer test, BLCA-1, BLCA-4, hyaluronic acid, hyaluronidase, 
Lewis X antigen, microsatellite analysis, Quanticyt, soluble Fas, Survivin, and 
telomerase). The biological foundation, methodologies, and diagnostic 
performance of the biomarkers are discussed. The characteristics of the 
biomarkers are compared to urine cytology. At this time, urine biomarkers are 
utilized in a variety of clinical situations but their role is not well defined. 
The goal of identifying an optimal marker that will replace cystoscopy and/or 
cytology is still ongoing.