Urinary tumor markers are proposed for use in the evaluation of individuals who have signs and/or symptoms of bladder cancer to inform a decision whether to proceed to cystoscopy and biopsy. In addition, there has been recent interest in using urinary tumor markers as a noninvasive screening tool for precancerous colon polyps.
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, and 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% to 100%), its sensitivity is lower, ranging from 50% to 60% overall, and is considered even lower for low-grade tumors. Therefore, interest has been reported in identifying tumor markers in voided urine that would provide a more sensitive and objective test for tumor recurrence.
There are several commercially available tests that have received clearance by the U.S. Food and Drug Administration. These tests are indicated as adjuncts to standard procedures for use in the initial diagnosis of bladder cancer or surveillance of individuals with bladder cancer. Some of these tests are listed below.
Aura Tek FDP Test™
BTA stat® test
BTA TRAK® test
UroVysion® Bladder Cancer Kit
Screening for polyps is currently conducted by colonoscopy, with recommended screening every ten years beginning at age 50. Colonoscopy is invasive and results in poor compliance with screening recommendations. The availability of a noninvasive test to detect precancerous polyps is currently in development using urinary biomarkers. PolyDx is a urine metabolite assay that uses an algorithm to compare urine metabolite concentrations to determine the likelihood of colonic adenomatous polyps. This test is at a very early stage of development. Currently, there is insufficient evidence on the diagnostic accuracy of urinary biomarkers to draw conclusions about its use to screen asymptomatic individuals for precancerous colon polyps.
The use of urinary biomarkers for the following indications is considered investigational:
Screening, diagnosis and/or monitoring of bladder cancer
Screening for precancerous colonic polyps
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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 http://www.auanet.org.
BlueCross BlueShield Association. Medical Policy Reference Manual. (6:2018). Urinary biomarkers for cancer screening, diagnosis, and surveillance. (2.04.07). Retrieved August 28, 2018 from BlueWeb. (16 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.
CMS.gov. Medicare & Medicaid Services. Palmetto GBA. (2018, March). Local Coverage Determination (LCD): Bladder/urothelial tumor markers (L33420). Retrieved August 29, 2018 from https://www.cms.gov.
Deng, L., Chang, D., Foshaug, R., Eisner, R., Tso, V., Wishart, D., & Fedorak, R. (2017). Development and validation of a high-throughput mass spectrometry based urine metabolomic test for the detection of colonic adenomatous polyps. Metabolites, 7 (3). Pii: E32. Doi: 10.3390/metabo7030032. (Level 4 evidence)
National Comprehensive Cancer Network. (2018, July). NCCN clinical practice guidelines in oncology (NCCN®) Bladder cancer (Version 5.2018). Retrieved August 29, 2018 from the National Comprehensive Cancer Network.
National Institute of Health and Care Excellence. (2015, February). Bladder cancer: diagnosis and management. Retrieved August 23, 2017 from www.nice.org.uk.
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)
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 http://www.accessdata.fda.gov.
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 http://www.accessdata.fda.gov.
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 http://www.accessdata.fda.gov.
U.S Preventive Services Task Force. (2011). Screening for bladder cancer: U.S. Preventive Services Task Force recommendation statement. Retrieved August 29, 2018 from https://www.uspreventiveservicestaskforce.org.
ORIGINAL EFFECTIVE DATE: 3/14/2013
MOST RECENT REVIEW DATE: 1/31/2019
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