Clinical evaluation of a multi-target fluorescent in situ hybridization assay for detection of bladder cancer

Purpose: The UroVysion fluorescence in situ hybridization assay (UroVysion Bladder Cancer Recurrence Kit, Vysis, Inc., Downers Grove, Illinois) is a multi-target assay that detects aneuploidy of chromosomes 3, 7 and 17, and loss of the 9p21 band in exfoliated cells in urine from patients with transitional cell carcinoma. We performed 2 multicenter trials. In 1 trial we compared the sensitivity of the FISH assay to the BTA Stat test (Bion Scientific, Redmond, Washington) and voided cytology in the detection of transitional cell carcinoma. In a separate study of healthy volunteers and patients with other (nontransitional cell carcinoma) conditions we determined the specificity of the FISH assay. Materials and Methods: A total of 176 patients with transitional cell carcinoma in the previous 9 months provided voided urine before cystoscopy. Each specimen was split, preserved and shipped to a central laboratory where all 3 tests were performed. All sites were blinded to results. Sensitivity calculations were based on central pathology review of resected tissue. Specificity was determined by testing 275 volunteers who were healthy and with nontransitional cell carcinoma conditions. Results: The 21 sites enrolled 176 patients with a history of transitional cell carcinoma, with 62 recurrences while undergoing surveillance. Overall sensitivities (with 95% CI) were FISH 71% (95% CI 58 to 82), BTA Stat test 50% (37 to 63) and cytology 26% (16 to 39). FISH was negative in 260 of the 275 healthy volunteers or patients with no history of transitional cell carcinoma (specificity 94.5%). Conclusions: Sensitivity of the FISH assay is superior to that of cytology and at least equivalent to the BTA Stat test in detecting recurrent transitional cell carcinoma. Its specificity approaches that of cytology. Further testing of its clinical use is warranted.