Impact of different grades of microscopic hematuria on the performance of urine-based markers for the detection of urothelial carcinoma

ObjectiveTo evaluate the performance of urine cytology (CYT), the UroVysion test [(fluorescence-in-situ-hybridization (FISH)], the uCyt+-test, and the nuclear matrix protein 22 ELISA (NMP22) at different grades of microscopic hematuria (HU) in a cohort of 2,365 patients suspicious for urothelial cell carcinoma (UCC).Patients and methodsA cohort of 2,365 consecutive patients suspected to have UCC underwent testing of at least 1 of the 4 noninvasive urine markers followed by cystoscopy, upper urinary tract imaging and, in case of suspicious findings, transurethral biopsy and/or resection of suspicious lesions. The grade of microscopic HU was determined by dipstick evaluation and urine microscopy and subdivided into 4 grades. The test results were compared with the HU status by contingency analysis and Cochran-Armitage test for trend separated for patients without evidence of UCC and with histologically proven UCC.ResultsIn case of grade 0, I, II, and III HU, rates of false positive CYT were 13.0, 17.4, 16.3, and 19.5% (P = 0.02), false negative CYT distributed 37.9, 18.5, 20.0, and 15.5% (P = 0.0003). FISH was false positive in 16.7, 19.8, 19.8, and 23.3% (P = 0.051) and false negative in 42.7, 27.5, 25.9, and 25.0% (P = 0.1). The uCyt+ was false positive in 12.5, 16.9, 24.0 and 35.1% (P < 0.0001), and false negative in 57.1, 26.4, 31.5, and 12.7% (P = 0.0003). NMP22 was false positive in 35.3, 55.3, 75.2, and 79.7% (P < 0.0001) and false negative in 50.0, 36.2, 22.6, and 8.2% (P < 0.0001).ConclusionThe extent of microscopic HU significantly influences the performance of noninvasive urine markers for UC. False positive rates of CYT, uCyt+, and NMP22 significantly increase with the degree of HU whereas false negative results of CYT, uCyt+, and NMP22 are less frequent in patients with high grade microscopic HU. These results underline the relevance of the grade of HU for the appropriate interpretation of urine tests.