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Molecular screening for bladder cancer: progress and potential

Abstract

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.

Key Points

  • The incidence of bladder cancer is on the rise, and mortality rates and overall prognosis have not changed dramatically for three decades, despite improved management

  • Detection of microhematuria could be a useful screening tool, but its specificity for bladder cancer is poor

  • Newer tests use urine as the source of markers of molecular change in, or altered products released from, bladder tumor cells

  • Some molecular tests are qualitative point-of-care assays, and some require specialized laboratory facilities for quantitative determination of marker alterations, while others enhance the quality of information gleaned from routine urine cytology

  • Using a combination of molecular tests, with or without cytology, could reduce the frequency of cystoscopy

  • Future bladder cancer screening algorithms will apply traditional and molecular tests in a stepwise fashion on the basis of an individual patient's risk of disease development

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Figure 1: Epidemiologic trends for bladder cancer in the USA.
Figure 2: Trends in pathologic stage-specific survival for bladder cancer in the USA.
Figure 3: Relative performance of major molecular detection tests for bladder cancer.
Figure 4: Proposed algorithm for screening and surveillance of bladder cancer.

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Mitra, A., Cote, R. Molecular screening for bladder cancer: progress and potential. Nat Rev Urol 7, 11–20 (2010). https://doi.org/10.1038/nrurol.2009.236

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