Cytology and Urinary Markers for the Diagnosis of Bladder Cancer

Primary detection and follow-up of patients with non–muscle-invasive (NMI) bladder cancer (BC) is done by urethro-cystoscopy (UCS) and, in most cases, cytology. Many urine-based tests have been developed, and in general, these tests have a higher sensitivity than cytology but a lower specificity. In this review, we assessed the value of urine tests for screening, primary detection, and surveillance of NMIBC. Considering the frequency of UCS for follow-up, having markers for recurrent BC would be especially useful. Therefore, we updated our systematic review to include five commonly studied urine markers (BTA stat, NMP22, uCyt + /Immunocyt, FISH UroVysion, and microsatellite analysis) and cytology for surveillance. The sensitivity and/or specificity of cytology and these five markers were more than 5% lower for patients under surveillance compared to the numbers reported in other reviews, confirming that the performance of urine markers and cytology is lower for the detection of recurrent BC than is UCS. Recent data from the first randomized trial to investigate the possibility of lowering UCS frequency with urinary microsatellite analysis showed substantial underestimation of sensitivity and specificity if the urologist was not aware of the urine test outcome. These results question but do not replace UCS as the gold standard for NMIBC surveillance. In conclusion, cytology is still important as an adjunct for the evaluation of patients with hematuria and the surveillance of patients with high-risk NMIBC. Urine markers other than cytology may play a role in future screening studies and the follow-up of patients with low-grade (G1–2) NMIBC.