Molecular markers in bladder cancer: A critical appraisal

The diagnosis of both primary and recurrent bladder tumors currently relies upon the urine cytology and cystoscopy. Neither of these diagnostic tools is completely accurate. Prognostication of bladder cancer is largely based on pathologic tumor grade and stage. Over the past 2 decades, there is accumulating evidence that like many other cancers, bladder cancer, too, has a distinct molecular signature that separates it from other cancers and normal bladder tissue. Bladder tumors of different grades and stages even possess unique, and specific genotypic and phenotypic characteristics. Although recognition of several of these molecular alterations is possible by analyzing tumor tissue, urine, and serum samples, few if any of these "molecular markers" for bladder cancer are widely used in clinical practice. These markers include some that can be applied during the diagnostic work-up of symptoms (e.g., hematuria), those under surveillance for recurrence of superficial disease and forecasting long-term prognosis, or response to chemotherapy. In this review of molecular markers for bladder cancer, effectiveness of markers in each of these categories that are identifiable in the urine of patients with bladder cancer was examined. Many of the diagnostic markers appear to hold an advantage over urine cytology in terms of sensitivity, especially for the detection of low-grade superficial tumors. However, most markers tend to be less specific than cytology, yielding more false-positives. This result is more commonly observed in patients with concurrent bladder inflammation or other benign bladder conditions. Although there are several candidate markers for assessing prognosis or response to chemotherapy, studies of large patient populations are lacking. Further studies involving larger numbers of patients are required to determine their accuracy and widespread applicability in guiding treatment of bladder cancer. (C) 2006 Elsevier Inc. All rights reserved.