Urinary Biomarkers in Bladder Cancer: Where Do We Stand?

Abhishek Bhat; Chad R. Ritch


Curr Opin Urol. 2019;29(3):203-209. 

In This Article

Abstract and Introduction


Purpose of review: To provide a current comprehensive review of the available urinary biomarkers for the detection and surveillance of bladder cancer.

Recent findings: The limitations of urine cytology and invasive nature of cystoscopic evaluation have led to a growing search for an ideal, cost-effective biomarker with acceptable sensitivity and specificity. Current FDA approved biomarkers such as UroVysion fluorescent in situ hybridization, Immunocyt, and nuclear matrix protein 22 do not have the specificity, and thus positive predictive value to warrant their cost as a routine adjunct or replacement for cystoscopy. Several promising commercially available assays such as Cxbladder, Assure MDx, and Xpert BC may perform better than cytology in select populations. Novel genomic, epigenetic, inflammatory, and metabolomic-based assays are being analyzed as potential urinary biomarkers.

Summary: Urinary biomarkers with high sensitivity and specificity are an unmet need in bladder cancer. Several new assays may meet these criteria and future research may justify use in clinical practice.


The standard diagnostic workup for bladder cancer involves cystoscopy, contrast-enhanced computed tomography (CT) scan, or MRI. Cystoscopy and imaging have limited sensitivity for the detection of small lesions in the urinary tract; therefore, many urologists rely on urine cytology as an adjunctive test. However, urine cytology is hindered by low sensitivity, sampling error during extraction, variable quality in processing of urine, and interobserver variability in cytopathologic interpretation. The role of cytology as a urinary biomarker is therefore limited to a few scenarios, where the test may be perform with acceptable sensitivity and specificity, such as in surveillance of high-risk nonmuscle invasive bladder cancer (NMIBC) or the assessment of response to intravesical therapy.[1]

A comprehensive review of urine cytology demonstrates a low sensitivity ranging from 20 to 53%, and a specificity of 83–99%.[2] Despite the aforementioned shortcomings, from a practical perspective, urine cytology remains the most widely used urinary biomarker because of the ease of use. However, there is a dire need for a urinary biomarker with improved sensitivity and specificity such that urologists can minimize invasive procedures for the diagnosis of bladder cancer. The purpose of this article is to summarize the current landscape of urinary biomarkers and to provide a concise review of the latest advancements in the field.