Sensitivity and specificity of commonly available bladder tumor markers versus cytology: Results of a comprehensive literature review and meta-analyses

Objectives. To determine the clinical utility of urine-based bladder tumor markers (UBBTMs) and cytology in the treatment of patients with transitional cell carcinoma on the basis of their statistical performance. Methods. A comprehensive literature review was performed using Medline (1966 to current) and other search engines. Data regarding the statistical performance of UBBTMs were double extracted and rectified. Studies addressing comparable patient populations were combined and hierarchical Bayesian meta-analyses performed to calculate the sensitivity and specificity of commonly used UBBTMs, as well as urinary cytology. Patient populations were stratified by tumor stage and grade when data were presented in an extractable fashion. Results. The literature review yielded 54 publications, 338 distinct patient groups (controls, screening population, patients with cancer, strata based on grade and stage) and more than 10,000 patients. The number of groups varied from 1 to 18, and the number of patients ranged from less than 100 to more than 1500 for the various markers. All UBBTMs have better sensitivity compared with cytology, especially for low-grade/stage disease, but do not match cytology regarding specificity. In patients with grade 1 and 2 tumors, several UBBTMs are significantly superior statistically in terms of sensitivity compared with cytology. The sensitivity for transitional cell carcinoma in situ (Tis) is surprisingly poor for all UBBTMs. Conclusions. UBBTMs can be used for follow-up of low-grade/stage tumors but should not replace cystoscopy. All UBBTMs have better sensitivity than cytology and could potentially replace routine cytology during patient follow-up.