The current system used to classify bladder carcinoma by stage and histological grade is very useful, yet still has limited ability to predict the natural history, or treated natural history, of a bladder tumor. Cystoscopy and urine cytology are currently the gold standard in the diagnosis and follow–up of bladder cancer. Classical urine cytology, however, at least in the diagnosis of G1 tumors, is definitely characterized by a relative low sensitivity. The low sensitivity and subjective interpretation of cytology led to the development of several tests to detect bladder cancer in urine. We provide a current, comprehensive review of the literature on bladder tumor markers and summarize their diagnostic potential. In conclusion, under the premise that cystoscopy has never been subjected to evaluation, no diagnostic marker with a sensitivity and specificity comparable to cystoscopy currently exists. The combined analysis of several tumor markers, as in the Immunocyt test, seems to be the most promising approach. In the future, rather highly sensitive tests may be able to replace cystoscopy or prolong the intervals of cystoscopies in the follow–up of selected patients.

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