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Carcinoma of the urinary bladder is a common malignancy and a major cause of morbidity and mortality in the western world. Current understanding of etiology, disease process, molecular characteristics and management principles make urothelial carcinoma an ideal candidate for screening. The capacity of traditional noninvasive diagnostic procedures such as microhematuria testing and urine cytology to be used as stand-alone screening techniques is limited, however. New qualitative and quantitative molecular screening modalities can detect cellular and subcellular alterations that are often exclusively associated with urothelial carcinoma. Such alterations can be detected in a noninvasive manner, using urine as a marker source, with reasonable sensitivity and specificity. Application of several molecular assays in conjunction with traditional screening methods has had promising results. We propose an evidence-based and risk-based approach to future bladder cancer screening. Such an approach would harness the reasonable sensitivity, ease of use and cost-effectiveness of microhematuria testing, plus the specificity of molecular tests, to target high-risk populations for screening. The ultimate goals are to identify susceptible individuals, detect bladder tumors before they invade using unobtrusive and cost-effective methods, and optimize surveillance strategies for long-term follow-up.