BlueCross BlueShield of Tennessee Medical Policy Manual

Urinary Tumor Markers for Bladder Cancer


Urinary bladder cancer, a relatively common form of cancer in the United States, results in significant morbidity and mortality. Bladder cancer (urothelial carcinoma), typically presents as a tumor confined to the superficial mucosa of the bladder. The most frequent symptom of early bladder cancer is hematuria; however, urinary tract symptoms (i.e., urinary frequency, urgency, dysuria) may also occur.

The diagnosis of bladder cancer is generally made by cystoscopy and biopsy. Due to high frequency of recurrence of disease, follow-up cystoscopies along with urine cytology are employed for periodic surveillance to identify recurrence early. While urine cytology is a specific test (from 90-100%), its sensitivity is lower, ranging from 50-60% overall and is considered even lower for low-grade tumors. However, according to the current National Comprehensive Cancer Network (NCCN®) Guidelines for Bladder Cancer “…it remains unclear whether these tests offer additional information that is useful for detection and management of bladder tumors.”

More than 30 urinary biomarkers have been reported for use in bladder cancer diagnosis, a few that are commercially available include the following:




The sensitivity and specificity of various urinary tumor markers in the diagnosing and/or monitoring of bladder cancer have been studied. There is little evidence that the results of tumor marker tests have a measurable impact on patient management (e.g., the frequency of cystoscopy) or on health outcomes to date. There is also a lack of evidence that tumor markers for detection of bladder cancer are clinically useful as screening tools in asymptomatic individuals.


American Urological Association. (2016). Diagnosis and treatment of non-muscle invasive bladder cancer: AUA/SUO guideline. Retrieved September 27, 2016 from 

BlueCross BlueShield Association. Medical Policy Reference Manual. (6:2017). Urinary tumor markers for bladder cancer. (2.04.07). Retrieved August 23, 2017 from BlueWeb. (22 articles and/or guidelines reviewed)

Chou, R., Gore, J. L., Buckley, D., Fu, R., Gustafson, K., Griffin, J. C., et al. (2015). Urinary biomarkers for diagnosis of bladder cancer: a systematic review and meta-analysis. Annals of Internal Medicine, 163 (12), 922-931. Abstract retrieved September 27, 2016 from PubMed database.

First Coast Service Options, Inc. (2015, October). Local Coverage Determination (LCD): Urinary tumor markers for bladder cancer (L33965). Retrieved August 23, 2017 from

Hosseini, J., Golshan, A., Mazloomfard, M., Mehrsai. A., Zargar. M., Ayati. M., et al. (2010). Detection of recurrent bladder cancer NMP22 test or urine cytology? Urology Journal, 9 (1), 367 - 372. (Level 1 evidence - Independent study)

Meo, A., Bartlett, J., Cheng, Y., Pasic, M., and Yousef, G. (2017). Liquid biopsy: a step forward towards precision medicine in urologic malignancies. Molecular Cancer, 16, 80. (Level 2 evidence)

National Comprehensive Cancer Network. (2017, May). NCCN clinical practice guidelines in oncology (NCCN®) Bladder cancer (Version 5.2017). Retrieved August 23, 2017 from .

National Institute of Health and Care Excellence. (2015, February). NICE guideline: bladder cancer: diagnosis and management. Retrieved August 23, 2017 from

Parker, J. & Spiess, P. (2011). Current and emerging bladder cancer urinary biomarkers. The Scientific World Journal: Urology, 11, 1103-1112. (Level 5 evidence)

Shariat, S., Savage, C., Chromecki, T., Sun, M., Scherr, D., Lee, R., et al. (2011). Assessing the clinical benefit of NMP22 in the surveillance of patients with non–muscle-invasive bladder cancer and negative cytology: a decision-curve analysis. Cancer, 117 (13), 2892-2897. (Level 3 evidence - Independent study)

U. S. Food and Drug Administration. (1998, April). Center for Devices and Radiological Health. 510(k) Premarket Notification Database.K971402 (BTA TRAK®). Retrieved September 27, 2016 from

U. S. Food and Drug Administration. (2000, February). Center for Devices and Radiological Health. 510(k) Premarket Notification Database. K994356 (Immunocyte®). Retrieved September 27, 2016 from

U. S. Food and Drug Administration. (2002, July). Center for Devices and Radiological Health. 510(k) Premarket Notification Database. K021231 (NMP22® BladderCheck® Kit). Retrieved August 31, 2012 from 

U.S. Preventive Services Task Force. (2014). Guide to clinical preventative services, 2017, bladder cancer. Retrieved August 23, 2017 from




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