FIG. 6:  Why do we need urine-based biomarkers?  First, cystoscopy is imperfect.  We can miss carcinoma in situ because the lesions can be non-discrete.  Small red patches are commonly seen in patients who are getting intravesical therapies, so we cannot discern from cystoscopy alone whether or not to be concerned. 

Second, we cannot visualize disease in the upper tracts.  When somebody has cancer in the lining of the kidney or the ureter, we cannot see it when we are looking in the bladder, but some substances, such as DNA, RNA, or proteins, might be shed in the urine that can be detected as urine markers. 

Third, the procedure is invasive.  Even though it is an office-based procedure, patients still perceive it as an invasive test, and they would prefer to avoid that. 

Another issue is that we currently use cytology, which is often inconsistent.  At least 20% of high-grade disease can be missed by cytology, and the results constitute a false-negative for most low-grade disease.  In 10-15% of cases there are atypical findings, which raise concern with both the physician and the patient, since they do not know whether the atypia represent cancer. 

Finally, cytology is not a point-of-care test, so the physician has to wait a week to get the results in most cases and then make the decision whether or not to do something differently.