Development of point-of-care tests for urinary bladder cancer - an historic review and view to future prospectives.

Abstract

Urine is an attractive biospecimen for noninvasive tests to facilitate bladder tumor diagnostics. Three different point-of-care (POC) tests based on lateral flow immunoassays (LFAs) are currently commercially available: UBC® Rapid Test, BTA stat®, and NMP22^TM BladderChek. The present review discusses these different tests based on their performance, clinical utility and the nature of the respective analytes. The level of sensitivities of UBC Rapid Test® and BTA stat® for detection of high-grade nonmuscle invasive bladder cancer using urine is in the order of 80%. Estimations of performance are highly dependent on patient selection criteria. UBC® Rapid Test shows a sensitivity of approximately 85% in patients presenting with macrohematuria which is the most common initial clinical symptom. Estimations of specificity are complicated by differences in how control groups are selected in different studies and are therefore more difficult to compare between published reports. Different POC tests differ with regard to the source of the analytes that are measured. The BTA Stat® test is based on detection of plasma proteins (Factor H/Factor H-related proteins), potentially leading to a lack of specificity during conditions of renal dysfunction. A large number of analytes to be used for urine-based bladder cancer tests have been described in the literature, including cytokines and proteases implicated in tumor invasion. These proteins, although biologically relevant, are often present at very low levels in urine that may be unsuitable for development of LFAs. Release of abundant intracellular structural proteins from cells such as cytokeratins (UBC® Rapid Test) and nuclear matrix proteins (NMP22^TM) may therefore be advantageous. We conclude that available data support the use of urine-based POC tests as adjuncts during the clinical work up of suspected bladder cancer.