Current bladder tumor tests: does their projected utility fulfill clinical necessity?

PURPOSE: We reviewed currently available bladder cancer tests in the context of the clinical expectations of a noninvasive bladder cancer test.
MATERIALS AND METHODS: We reviewed the literature on bladder cancer tests that are commercially available or have shown clinical usefulness and examined how each test compares with standard methods of bladder cancer diagnosis.
RESULTS: The clinical necessity for a noninvasive test for bladder cancer is 2-fold, including the early detection of high grade bladder tumors before muscle invasion and monitoring tumor recurrence or new onset. An ideal noninvasive test should be sensitive, specific, rapid, technically simple and have low intra-assay and interassay variability. Urine cytology has high specificity but limited applicability due to its relatively low sensitivity and subjective nature. Hematuria detection by Hemastix dipstick is sensitive but not specific for detecting bladder cancer. Molecules associated with bladder tumor growth and progression may serve as a basis for designing noninvasive diagnostic tests. The Food and Drug Administration approved BTA Stat and BTA TRAK tests, which detect human complement factor H and a related protein in urine, have 60% to 80% sensitivity and 50% to 70% specificity (lower in symptomatic patients) for bladder cancer. The Food and Drug Administration approved NMP22 test, which measures the level of nuclear mitotic apparatus protein in urine, has 50% to 100% sensitivity and 60% to 90% specificity. Accu-Dx detects fibrin degradation products, fibrin and fibrinogen in urine, although this test is no longer commercially available. The Immunocyt test combines cytology with an immunofluorescence technique to improve the sensitivity of cytology for detecting low grade tumors. The telomeric repeat amplification protocol assay for telomerase in exfoliated cells has 70% to 86% sensitivity and 60% to 90% specificity for bladder cancer. However, the low stability of telomerase in urine affects its sensitivity. The hyaluronic acid and hyaluronidase (HA-HAase) test, which measures the urinary level of hyaluronic acid and hyaluronidase, has 90% to 92% sensitivity and 80% to 84% specificity for bladder cancer. Quanticyt karyometry evaluates nuclear shape and DNA content of exfoliated cells to detect bladder cancer. The list of bladder tumor markers is growing rapidly and large multicenter trials are essential to assess their usefulness.
CONCLUSIONS: Although currently noninvasive bladder cancer tests cannot replace cystoscopy, some have shown a promise of being clinically useful. One or a combination of these tests-markers may prove to be a prostate specific antigen for bladder cancer provided that patients and, more importantly, clinicians accept it.