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Medical Policy: 02.04.36
Original Effective Date: December 2011
Reviewed:
Revised:
Benefit Application
Benefit determinations are based on the applicable contract language in effect at the time the
services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary
based on contract, and individual member benefits must be verified. Wellmark determines medical
necessity only if the benefit exists and no contract exclusions are applicable. This medical
policy may not apply to FEP. Benefits are determined by the Federal Employee Program.
This Medical Policy document describes the status of medical technology at the time the document
was developed. Since that time, new technology may have emerged or new medical literature may
have been published. This Medical Policy will be reviewed regularly and be updated as scientific
and medical literature becomes available.
Description:
The diagnosis of bladder cancer is generally made by cystoscopy and biopsy. Additionally, bladder cancer has a very high frequency of recurrence and therefore requires follow-up cystoscopies, along with urine cytology, as periodic surveillance to detect recurrence early. Consequently, urine biomarkers that might be used to either supplement or supplant these tests have been actively investigated.
Urinary bladder carcinoma, the fourth most common cancer in men and the ninth most common cancer in women, results in significant morbidity and mortality. Bladder cancer typically presents as a tumor confined to the superficial mucosa of the bladder. The most common symptom of early bladder cancer is hematuria; however, other urinary symptoms such as frequency, urgency, and dysuria may also occur. Most urologists follow the American Urological Association (AUA) guidelines for hematuria, which recommend cystoscopic evaluation of all adults older than age 40 years presenting with microscopic hematuria, and for those younger than age 40 years presenting with risk factors for developing bladder cancer. Confirmatory diagnosis of bladder cancer must be made by cystoscopic examination, which is considered the gold standard, and biopsy. At initial diagnosis, approximately 70% of patients have cancers confined to the epithelium or subepithelial connective tissue. Non-muscle invasive disease is usually treated with transurethral resection, with or without intravesical therapy, depending on depth of invasion and tumor grade. However, a 75% incidence of recurrence has been noted in these patients, with 10% to 15% progressing to muscle invasion over a 5-year period. Current follow-up protocols include flexible cystoscopy and urine cytology every 3 months for 1 to 3 years, every 6 months for an additional 2 to 3 years, and then annually thereafter, assuming no recurrence. 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. Therefore, there has been considerable interest in identifying tumor markers in voided urine that would provide a more sensitive and objective test for tumor recurrence.
The BTA (bladder tumor antigen) stat® test (Polymedco Inc., Cortlandt Manor, NY) is a qualitative, point-of-care rest with an immediate result that identifies a human complement factor H-related protein that was shown to be produced by several human bladder cell lines but not by other epithelial cell lines.
The BTA stat® test is an in vitro immunoassay intended for the qualitative detection of bladder tumor-associated antigen in the urine of persons diagnosed with bladder cancer. The BTA TRAK® test (Polymedco Inc., Cortlandt Manor, NY) provides a quantitative determination of the same protein. This test requires trained personnel and a reference laboratory. Both these tests have sensitivities comparable to that of cytology for high-grade tumors and better than cytology for low-grade tumors.
Nuclear matrix protein 22 (NMP-22) is a protein associated with the nuclear mitotic apparatus. It is thought that this protein is released from the nuclei of tumor cells during apoptosis. Normally, only very low levels of NMP-22 can be detected in the urine, and elevated levels may be associated with bladder cancer. NMP-22 may be detected in the urine using an immunoassay.
Florescence in situ hybridization (FISH) DNA probe technology has also been used to detect chromosomal abnormalities in voided urine to assist not only in bladder cancer surveillance but also in the initial identification of bladder cancer. FISH DNA probe technology is a technique to visualize nucleic acid sequences within cells by creating short sequences of fluorescently labeled, single-strand DNA, called probes, which match target sequences. The probes bind to complimentary strands of DNA, allowing for identification of location of the chromosomes targeted. UroVysion® (Vysis Inc., Downers Grove, IL) is a commercially available FISH test.
The ImmunoCyt™ test (DiagnoCure Inc., Quebec) uses fluorescence immunohistochemistry with antibodies to a mucin glycoprotein and a carcinoembryonic antigen (CEA). These antigens are found on bladder tumor cells. The test is used for monitoring bladder cancer in conjunction with cytology and cystoscopy.
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Prior Approval:
Not applicable
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Policy:
Initial diagnosis
The following urinary bladder tumor markers may be considered medically necessary as an adjunct in the diagnosis of bladder cancer only in conjunction with current standard diagnostic procedures:
- BTA stat, BTA TRAK
- NMP22, NMP22 BLADDER CHEK
- UroVysion
The following urinary bladder tumor marker is considered investigational in the diagnosis of bladder cancer
Bladder cancer monitoring
The following urinary bladder cancer tumor markers may be considered medically necessary as an adjunct in the monitoring of bladder cancer only in conjunction with current standard monitoring procedures:
- BTA stat, BTA TRAK
- ImmunoCyt
- NMP22, NMP22 BLADDER CHEK
- UroVysion
Screening for bladder cancer in asymptomatic persons
The use of urinary bladder cancer tumor markers is considered investigational for screening for bladder cancer in asymptomatic persons.
The use of all other urinary bladder cancer tumor markers is considered investigational in the diagnosis, monitoring, or screening for bladder cancer.
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Procedure Codes and Billing Guidelines:
- To report provider services, use appropriate CPT* codes, Modifiers, Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or ICD-9-CM diagnostic codes.
- 88120 Cytopathology, in situ hybridization (e.g., FISH), urinary tract specimen for morphometric analysis, 3-5 molecular probes, each specimen, manual
- 88121 Cytopathology, in situ hybridization (e.g., FISH), urinary tract specimen for morphometric analysis, 3-5 molecular probes, each specimen, using computer-assisted technology
- 86294 Immunoassay for tumor antigen, qualitative or semiquantitative (eg, bladder tumor antigen)
- 86386 Nuclear Matrix Protein 22 (NMP22), qualitative
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Selected References:
- Mowatt G, Zhu S, Kilonzo M et al. Systematic review of the clinical effectiveness and cost-effectiveness of photodynamic diagnosis and urine biomarkers (FISH, ImmunoCyt, NMP22) and cytology for the detection and follow-up of bladder cancer. Health Technol Assess 2010; 14(4):1-331.
- Raitanen MP, FinnBladder Group The role of BTA stat test in follow up of patients with bladder cancer: results from FinnBladder studies. World J Urol 2008; 26(1):45-50.
- Sarosdy MF, Schellhammer P, Bokinsky G et al. Clinical evaluation of a multi-target fluorescent in situ hybridization assay for detection of bladder cancer. J Urol 2002; 168(5):1950-4.
- Horstmann M, Patschan O, Hennenlotter J et al. Combinations of urine-based tumor markers in bladder cancer surveillance. Scand J Urol Nephrol 2009; 43(6):461-6.
- Sullivan PS, Nooraie F, Sanchez H et al. Comparison of ImmunoCyt, UroVysion and urine cytology in detection of recurrent urothelial carcinoma. Cancer Cytopathol 2009; 117(3):167-73.
- Kamat AM, Karan JA, Grossman B et al. Prospective trial to identify optimal bladder cancer surveillance protocol: reducing costs while maximizing sensitivity. BJU International 2011 [Epub ahead of print].
- Eissa S, Swellam M, Shehata H et al. Expression of HYAL1 and survivin RNA as diagnostic molecular markers for bladder cancer. J Urol 2010; 183(2):493-8.
- Chou R, Dana T. Screening adults for bladder cancer: a review of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2010; 153(7):461-8.
- Lotan Y, Elias K, Svatek RS et al. Bladder cancer screening in a high risk asymptomatic population using point of care urine based protein tumor marker. J Urol 2009; 182(1):52-8.
- Sturgeon CM, Duffy MJ, Hoffmann BR et al. National Academy of Clinical Biochemistry Laboratory Medicine Clinical Practice Guidelines for use of tumor markers in liver, bladder, cervical, and gastric cancers. Clin Chem 2010 Jun; 56(6):e1-48. Epub 2010 Mar 5.
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Policy History:
Date Reason Action
December 2011 Literature review New policy
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Wellmark medical policies address the complex issue
of technology assessment of new and emerging treatments, devices,
drugs, etc. They are developed to
assist in administering plan benefits and constitute neither offers of
coverage nor medical advice. Wellmark medical policies contain only a
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and, therefore, cannot guarantee any results or outcomes.
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*Current Procedural Terminology © 2010 American Medical Association. All Rights Reserved.
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