This Medical Policy is provided for informational purposes only.

If Members have any questions about the medical necessity of a service or procedure, they should discuss the question with their Network Provider or call a member of our Customer Service Team.

MEDICAL POLICY USE DISCLAIMER

  1. Medical Policy is used by Blue Cross & Blue Shield of Mississippi, A Mutual Insurance Company ("BCBSMS") as one set of guidelines (among other sets of guidelines) to assist BCBSMS in making benefit coverage decisions. BCBSMS utilizes Medical Policy adopted by our Medical Policy Advisory Committee ("MPAC") which is supported by the Blue Cross and Blue Shield Association Medical Policy, research and development. Medical Policies are the property of BCBSMS and any use of Medical Policy not agreed to by BCBSMS is strictly prohibited. The use of Medical Policy for purposes related to the health care of a BCBSMS plan member is permitted and is not a violation of the proprietary rights of BCBSMS.
  2. These Medical Policies are based on scientifically meritorious evidence provided through research for a particular medical technology. Medical Policy is also based on data from peer-reviewed scientific literature, from criteria developed by specialty societies and from guidelines adopted by other health care organizations.
  3. These Medical Policies apply to members/subscribers who have health insurance through BCBSMS. This Medical Policy also applies to Members of a self-insured group health plan for which Blue Cross & Blue Shield of Mississippi provides claims administration and persons covered by a Medicare Supplement policy offered by BCBSMS. This Medical Policy does not apply to any other individuals. Medical Policies may differ for Federal employees covered under the Federal Employees Health Benefits Plan.
  4. In the event of any conflict between this Medical Policy and any benefit plan, Summary Plan Description or other coverage document, the benefit plan, Summary Plan Description or other coverage document will govern.
  5. Medical technology is rapidly changing and these Medical Policies are subject to change without notice. Also, please be aware that as a result of ongoing changes being made to Medical Policy, BCBSMS cannot and does not guarantee that these Medical Policies are current.

BCBSMS Medical Policies are Subject to the Following Restrictions


This Medical Policy is provided for informational purposes only.

If Members have any questions about the medical necessity of a service or procedure, they should discuss the question with their Network Provider or call a member of our Customer Service Team.

MEDICAL POLICY USE DISCLAIMER

  1. Medical Policy is used by Blue Cross & Blue Shield of Mississippi, A Mutual Insurance Company ("BCBSMS") as one set of guidelines (among other sets of guidelines) to assist BCBSMS in making benefit coverage decisions. BCBSMS utilizes Medical Policy adopted by our Medical Policy Advisory Committee ("MPAC") which is supported by the Blue Cross and Blue Shield Association Medical Policy, research and development. Medical Policies are the property of BCBSMS and any use of Medical Policy not agreed to by BCBSMS is strictly prohibited. The use of Medical Policy for purposes related to the health care of a BCBSMS plan member is permitted and is not a violation of the proprietary rights of BCBSMS.
  2. These Medical Policies are based on scientifically meritorious evidence provided through research for a particular medical technology. Medical Policy is also based on data from peer-reviewed scientific literature, from criteria developed by specialty societies and from guidelines adopted by other health care organizations.
  3. These Medical Policies apply to members/subscribers who have health insurance through BCBSMS. This Medical Policy also applies to persons covered by the Mississippi Children's Health Insurance Program, Members of a self-insured group health plan for which Blue Cross & Blue Shield of Mississippi provides claims administration and persons covered by a Medicare Supplement policy offered by BCBSMS. This Medical Policy does not apply to any other individuals. Medical Policies may differ for Federal employees covered under the Federal Employees Health Benefits Plan.
  4. In the event of any conflict between this Medical Policy and any benefit plan, Summary Plan Description or other coverage document, the benefit plan, Summary Plan Description or other coverage document will govern.
  5. Medical technology is rapidly changing and these Medical Policies are subject to change without notice. Also, please be aware that as a result of ongoing changes being made to Medical Policy, BCBSMS cannot and does not guarantee that these Medical Policies are current.

BCBSMS Medical Policies are Subject to the Following Restrictions


This Medical Policy is provided for informational purposes only.

If Members have any questions about the medical necessity of a service or procedure, they should discuss the question with their Network Provider or call a member of our Customer Service Team.

MEDICAL POLICY USE DISCLAIMER

  1. Medical Policy is used by Blue Cross & Blue Shield of Mississippi, A Mutual Insurance Company ("BCBSMS") as one set of guidelines (among other sets of guidelines) to assist BCBSMS in making benefit coverage decisions. BCBSMS utilizes Medical Policy adopted by our Medical Policy Advisory Committee ("MPAC") which is supported by the Blue Cross and Blue Shield Association Medical Policy, research and development. Medical Policies are the property of BCBSMS and any use of Medical Policy not agreed to by BCBSMS is strictly prohibited. The use of Medical Policy for purposes related to the health care of a BCBSMS plan member is permitted and is not a violation of the proprietary rights of BCBSMS.
  2. These Medical Policies are based on scientifically meritorious evidence provided through research for a particular medical technology. Medical Policy is also based on data from peer-reviewed scientific literature, from criteria developed by specialty societies and from guidelines adopted by other health care organizations.
  3. These Medical Policies apply to members/subscribers who have health insurance through BCBSMS. This Medical Policy also applies to persons covered by the Mississippi Children's Health Insurance Program, Members of a self-insured group health plan for which Blue Cross & Blue Shield of Mississippi provides claims administration and persons covered by a Medicare Supplement policy offered by BCBSMS. This Medical Policy does not apply to any other individuals. Medical Policies may differ for Federal employees covered under the Federal Employees Health Benefits Plan.
  4. In the event of any conflict between this Medical Policy and any benefit plan, Summary Plan Description or other coverage document, the benefit plan, Summary Plan Description or other coverage document will govern.
  5. Medical technology is rapidly changing and these Medical Policies are subject to change without notice. Also, please be aware that as a result of ongoing changes being made to Medical Policy, BCBSMS cannot and does not guarantee that these Medical Policies are current.

BCBSMS Medical Policies are Subject to the Following Restrictions

Medical Policy Search
Printer Friendly Version Urinary Tumor Markers for Bladder Cancer

Urinary Tumor Markers for Bladder Cancer

 

DESCRIPTION

 The diagnosis of bladder cancer is generally made by cystoscopy and biopsy. Moreover, bladder cancer has a very high frequency of recurrence and therefore requires follow-up cystoscopies, along with urine cytology, as periodic surveillance to identify 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 ninth most common in women 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 common symptom of early bladder cancer is hematuria; however, urinary tract symptoms (i.e., urinary 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 greater than 40 years old with microscopic hematuria and for those less than 40 years old with risk factors for developing bladder cancer. Confirmatory diagnosis of bladder cancer must by made by cystoscopic examination and biopsy which is considered to be the “gold standard.”

At initial diagnosis, about 70 percent 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, there is a 75 percent incidence of recurrence in these patients with 10-15 percent progressing to muscle invasion over a five year period. Current follow-up protocols include flexible cystoscopy and urine cytology every three months for one to three years, every six months for an additional two to three years, and then annually, assuming no recurrence.

While urine cytology is a specific test (from 90 percent–100 percent), its sensitivity is lower, ranging from 50 percent–60 percent overall and is considered even lower for low-grade tumors. Therefore, there has been interest in identifying tumor markers in voided urine that would provide a more sensitive and objective test for tumor recurrence.

Tests cleared by the U.S. Food and Drug Administration (FDA):

The BTA (bladder tumor antigen) stat®test, (Polymedco Inc., Cortlandt Manor, NY) is a qualitative, point-of-care test 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 tests have sensitivities comparable to that of cytology for high-grade tumors and better than cytology for low-grade tumors.

Fluorescence 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 complementary strands of DNA, allowing for identification of the location of the chromosomes targeted. UroVysion® (Vysis Inc., Downers Grove, IL) is a commercially available FISH test.

The ImmunoCytTM 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.

In addition to the FDA-cleared tests, Predictive Biosciences (Lexington, MA) is marketing a urine-based test, called CertNDxTM, to assess Fibroblast Growth Factor Receptor 3 (FGFR3) mutations. The test is intended to be used in combination with cytology for identifying patients with hematuria at risk of bladder cancer. It is being offered through Predictive Bioscience’s network of Clinical Laboratory Improvement Amendment (CLIA) laboratories. FGFR3 mutations may be associated with lower-grade bladder tumors that have a good prognosis.

Other urinary markers

A number of other urinary tumor markers, not currently commercially available in the United States, are under investigation. These include:

  • BLCA-1 and BCLA-4;
  • Hyaluronic acid and hyaluronidase;
  • Lewis X antigen;
  • Microsatellite markers;
  • Soluble Fas;
  • Survivin (can be isolated from urine and also from tumor samples);
  • Telomerase;
  • Cytokeratin 8, 18, 19, 20
  • Quanticyt

Urinary tumor marker tests cleared by the FDA and in clinical use include:

  • The quantitative BTA TRAK® and the qualitative point-of-care BTA (bladder tumor antigen) stat®test, both by Polymedco Inc., Cortlandt Manor, NY.
  • The quantitative immunoassay NMP22® and the qualitative, point-of-care test NMP22® BladderChek®, both by Matritech Inc., Newton, MA.
  • The UroVysion® Bladder Cancer Kit (Vysis Inc., Downers Grove, IL), a FISH test.
  • The ImmunoCytTM test, also marketed as UCyt+TM (DiagnoCure Inc., Quebec).

With the exception of the ImmunoCyt test, which is only cleared for monitoring bladder cancer recurrence, all tests are FDA-cleared as adjunctive tests for use in the initial diagnosis of bladder cancer and surveillance of bladder cancer patients, in conjunction with standard procedures.

Discussion of other Serum Tumor Markers is addressed in a separate policy.

 

POLICY

 The use of urinary tumor markers is considered investigational in the diagnosis of, monitoring, and/or screening for bladder cancer.

 

POLICY EXCEPTIONS

 Federal Employee Program (FEP) may dictate that all FDA-approved devices, drugs or biologics may not be considered investigational and thus these devices may be assessed only on the basis of their medical necessity.

 

POLICY GUIDELINES

 For the purpose of this policy, standard diagnostic procedures for bladder cancer consist of urine cytology and cystoscopy, with or without biopsy.

Investigative service is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized by certifying boards and/or approving or licensing agencies or published peer review criteria as standard, effective medical practice for the treatment of the condition being treated and as such therefore is not considered medically necessary.

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

 

POLICY HISTORY

 8/1999: Approved by Medical Policy Advisory Committee (MPAC)

6/28/2001: Coding Reference section updated, tables added, CPT codes 81000, 81001, 81002, 81003, 81005, 81007, 81015, 81020, 81099 added

11/2001: Reviewed by MPAC; Bladder Tumor Antigen or NMP-22 (Nuclear Matrix Protein 22) medically necessary

4/18/2002: Type of Service and Place of Service deleted

8/29/2003: Policy title "Bladder Tumor Antigen" renamed "Urinary Tumor Markers for Bladder Cancer, "Description" section updated to be consistent with BCBSA, NMP-22 added to the "Policy" and "Policy History" sections, Sources and Code Reference sections updated, ICD-9 diagnosis code range 188.0-188.9, 198.1 listed separately, CPT code range 81000-81020, 81099 listed separately, hyperlink moved to the "Description" section

4/7/2004: Code Reference section updated, CPT code 86316 deleted from covered code table, non-covered table and CPT codes 81000, 81001, 81002, 81003, 81005, 81007, 81015, 81020, 81099 deleted

3/15/2006:  Coding updated.  HCPCS 2006 revisions added to policy

12/04/2006: Description and policy section updated. Code Reference section updated. Added CPT code 83365, and ICD-9 code 599.7

4/29/2008: Policy reviewed, no changes

9/19/2008: Annual ICD-9 updates effective 10-1-2008 applied

7/24/2009: Policy Description section updated for clarification of the commercially available tumor biomarkers, Policy Statement section updated for clarification of the commercially available tumor biomarkers; and modified for FDA- approved uses, Policy Guidelines section updated, CPT Codes 86316, 88271, 88299, 88367, 88368 added to covered table, ICD-9 Diagnosis code V10.51 added to covered table, note added to CPT code 88299.

06/07/2010:  Policy description updated regarding available tests. Policy statement unchanged. FEP verbiage added to the Policy Exceptions section. The definition of investigative service added to the policy guidelines. Deleted outdated references from the Sources section.

03/07/2011:  Added new CPT codes 88120 and 88121 to the Code Reference section.

08/11/2011: Policy reviewed; no changes.

09/25/2012: Policy description updated regarding available tests. The medically necessary policy statements were deleted. Policy statement changed to state that the use of urinary tumor markers is considered investigational in the diagnosis of, monitoring, and/or screening for bladder cancer. The Code Reference section was changed to Non-Covered.

 

SOURCE(S)

 Blue Cross Blue Shield Association policy # 2.04.07

 

CODE REFERENCE

 This is not an all-inclusive list of non-covered procedure codes. All codes billed for this procedure are considered investigational and not eligible for coverage.

Non-Covered Codes

Code Number

Description

CPT-4

86294

Immunoassay for tumor antigen, qualitative or semiquantitative (e.g., bladder tumor antigen)

86316Immunoassay for tumor antigen; other antigen, quantitative, each
88120Cytopathology, in situ hybridization (eg, FISH), urinary tract specimen with morphometric analysis, 3-5 molecular probes, each specimen; manual  
88121 Cytopathology, in situ hybridization (eg, FISH), urinary tract specimen with morphometric analysis, 3-5 molecular probes, each specimen; using computer-assisted technology  
88271Molecular cytogenetics, DNA probe, each (e.g., FISH)
88299

Unlisted cytogenetic study

Note: Use the unlisted code to report the UroVysion® Bladder Cancer Test

88365

In situ hybridization (eg, FISH), each probe

88367Morphometric analysis, in situ hybridization (quantitative or semi-quantitative) each probe; using computer-assisted technology
88368Morphometric analysis, in situ hybridization (quantitative or semi-quantitative) each probe; manual

ICD-9 Procedure

 

 

ICD-9 Diagnosis

188.0 Malignant neoplasm of trigone of urinary bladder
188.1 Malignant neoplasm of dome of urinary bladder
188.2 Malignant neoplasm of lateral wall of urinary bladder
188.3 Malignant neoplasm of anterior wall of urinary bladder
188.4 Malignant neoplasm of posterior wall of urinary bladder
188.5 Malignant neoplasm of bladder neck
188.6 Malignant neoplasm of ureteric orifice
188.7 Malignant neoplasm of urachus
188.8 Malignant neoplasm of other specified sites of bladder
188.9 Malignant neoplasm of bladder, part unspecified

198.1

Secondary malignant neoplasm of other urinary organs

233.7

Carcinoma in situ of the bladder

236.7

Neoplasm of uncertain behavior

239.4

Neoplasm of unspecified nature, bladder

599.70, 599.71, 599.72Hematuria (new 10-1-2008)
V10.51Personal history of malignant neoplasm of bladder

HCPCS

 

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