Use of markers in defining urothelial premalignant and malignant conditions

Markers have revealed the presence of phenotypically abnormal areas in histologically benign urothelium in bladders containing transitional cell carcinomas. This finding strongly suggests that at least some bladder cancers are associated with changes in the field and that markers can detect these lesions before they reach a grossly malignant stage. Markers have been used clinically for the detection of cancer in patients who are under regular surveillance for recurrence of bladder cancer. Much less information is available regarding the use of markers to detect bladder cancer without a prior history of the disease and for the prediction of which tumors are biologically more aggressive. However, ongoing clinical trials are addressing the latter issue. The type of specimen and its preparation will determine what type of markers can be analyzed. Although marker performance is based upon sensitivity and specificity, the prevalence of bladder cancer in the population being tested will dramatically affect the positive predictive value of an assay. Markers with high positive predictive value are indicators for interventions, such as biopsy, while markers with high negative specific values are useful for avoiding interventions. Cytology is used to detect occult high-grade neoplasms such as carcinoma in situ. While not yet clinically validated, tests with high negative predictive value could be used to decrease the frequency of cystoscopic evaluation. Markers must be validated by testing them prospectively using previously defined cut-off values. Furthermore, markers that will be used to alter treatment should be tested prospectively to determine the safety and cost-effectiveness of this strategy. Recommendations for future work include: (1) evaluation of markers in patients with dysplasia defined by the current pathologic classification; (2) evaluation of markers as indicators of tumor recurrence; (3) evaluation of markers as indicators of tumor progression; and (4) evaluation of markers in chemoprevention studies.