DNA-based molecular cytology for bladder cancer surveillance
In Situ Hybridization, Fluorescence
Urinary Bladder Neoplasms
Surveillance strategies for urothelial cancer (UC) recurrence have historically relied on the diagnostic combination of cystoscopy and conventional urinary cytology. In this review, results of studies evaluating the role of the fluorescence in situ hybridization (FISH) assay in bladder cancer surveillance are critically examined. The published research on FISH compared with conventional cytology and cystoscopy for bladder cancer was identified using a Medline search and was critically analyzed. Sensitivity and specificity data were tabulated and compared. FISH outperformed conventional cytology across all stages and grades in all published reports, and it detected malignancy before the development of lesions visible by cystoscopy. Although overall sensitivity was 48% for cytology and 74% for FISH, its greatest advantage was in the detection of high-grade UC, including carcinoma in situ (CIS). Cumulative data from comparative studies showed the sensitivity of cytology compared with FISH was 19% versus 58% for grade 1, 50% versus 77% for grade 2, and 71% versus 96% for grade 3. Similar findings occurred by stage, where cytology compared with FISH sensitivity was 35% versus 64% for Ta, 66% versus 83% for T1, and 76% versus 94% for muscle-invasive carcinoma. Notably, cytology detected only 67% of CIS versus 100% detection by FISH. Specificity data were comparable. Unlike conventional urinary cytology and cystoscopy, which depend on subjective visible microscopic or macroscopic changes, FISH allows identification of chromosomal abnormalities associated with malignant development before phenotypic expression of those alterations. Use of morphologic cellular changes allows more rapid detection of such alterations, combining the benefits of conventional cytology with molecular diagnostics. It is apparent that we are in the early phases of realizing the potential of molecular diagnostics.