L29303-LCD

LCD/NCD Portal

Automated World Health

Local Coverage Determination (LCD) for Urinary Tumor Markers for Bladder Cancer (L29303)

Contractor Information

Contractor Name First Coast Service Options, Inc.

Contractor Number 09102

Contractor Type MAC - Part B

LCD Information

Document Information

LCD ID Number L29303

LCD Title Urinary Tumor Markers for Bladder Cancer

Contractor's Determination Number 86294

Primary Geographic Jurisdiction Florida

Oversight Region Region IV

AMA CPT/ADA CDT Copyright Statement

Applicable FARS/DFARS Apply to Government Use. Fee schedules, relative value units, conversion factors and/or related components are not assigned by the AMA, are not part of CPT, and the AMA is not recommending their use. The AMA does not directly or indirectly practice medicine or dispense medical services. The AMA assumes no liability for data contained or not contained herein. The Code on Dental Procedures and Nomenclature (Code) is published in Current Dental Terminology (CDT). Copyright © American Dental Association. All rights reserved. CDT and CDT-2010 are trademarks of the American Dental Association.

Original Determination Effective Date

For services performed on or after 02/02/2009 Original Determination Ending Date

Revision Effective Date

For services performed on or after 01/01/2011 Revision Ending Date

CMS National Coverage Policy N/A

Indications and Limitations of Coverage and/or Medical Necessity

Bladder cancer is the fifth most common cancer in the United States, with over 50,000 newly diagnosed cases and over 10,000 deaths annually. The diagnosis of primary and recurrent bladder cancer is one of the most difficult problems in urology and cytology. Ninety percent of bladder cancer cases are classified as transitional cell carcinomas (TCC), while the remaining 10% are predominantly squamous cell or adenocarcinomas. There are

four clinically relevant subgroups of TCC, as defined by pathologic staging carcinoma in situ (pTIS), non-invasive papillary TCC (pTa), minimally invasive TCC (pT1), and muscle invasive tumors (pT2-4). Each subgroup is distinct with respect to clinical outcome. At presentation, 75% of tumors are ‘superficial’ (i.e., pTa, pT1 or pTIS), of which 50% to 80% will have one or several recurrences, and 15% to 25% will progress to invasive tumors. The tumors with invasion limited to the lamina propria (stage pT1) pose the greatest clinical problem. Local progression to potentially life-threatening muscle-invasive cancer (pT2-4) occurs in 20% to 30% of these tumors after conservative surgical treatment.

After initial diagnosis and treatment, patients with urothelial carcinoma are routinely monitored every three months for the first two years then usually twice a year for three or more years. Up to 50% of patients will have recurrence of bladder cancer within five years. The current monitoring is done by cystoscopy , an invasive procedure, and by urine cytology. Standard cytology has been regarded as an additional diagnostic tool to select patients for cystoscopic evaluation. However, studies show that the sensitivity of cytology in urinary specimens is limited, since most of the noninvasive cancers (stage pTa) are missed. Therefore, cytology alone is unreliable to serve as a basis for therapy decisions.

Several diagnostic tests are available for the management of bladder cancer. Radioimmunoassay and immunohistochemical determinations of the serum levels of certain proteins or carbohydrates serve as tumor markers. When elevated, serum concentration of these markers may reflect tumor size and grade. Three other tests which are to be performed in conjunction with standard diagnostic procedures include:

The Urinary Fluorescence In Situ Hybridization (FISH) Test:

88120 Cytopathology, 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

The Bladder Tumor Antigen Stat (BSTAstat) Test:

86294 Immunoassay for tumor antigen, qualitative or semiquantitative (eg, bladder tumor antigen)

The Nuclear Matrix Protein 22 (NMP-22) Test:

86294 Immunoassay for tumor antigen, qualitative or semiquantitative (eg, bladder tumor antigen)

1. The Urinary FISH Test for recurrent bladder cancer is an FDA approved multitarget, multicolor fluorescence in situ hybridization (FISH) probe set that uses DNA technology designed to detect aneuploidy for chromosomes 3, 7, 17, and loss of the 9p21 locus in voided urine specimens from patients with transitional cell carcinoma of the bladder (urothelial carcinoma). In situ hybridization is a technique that allows the visualization of specific nucleic acid sequences within a cellular preparation. Specifically, DNA FISH involves the precise annealing of a single stranded fluorescently labeled DNA probe to complementary target sequences. The hybridization of the probe with the cellular DNA site is visible by direct detection using fluorescence microscopy. Results from this Urinary FISH Test are intended for use as a noninvasive method in the initial diagnosis of persons with hematuria suspected of having bladder carcinoma in conjunction with and not in lieu of current standard diagnostic procedures and] for monitoring tumor recurrence in conjunction with cystoscopy in patients previously diagnosed with bladder cancer.

Studies suggest that the sensitivity of the FISH assay for urothelial carcinoma (UC) is superior to urine cytology and yet maintains the high specificity of cytology. Studies also suggest that regular surveillance of UC patients for tumor recurrence with FISH could reduce UC mortality, because false negative urine cytology results place superficial UC patients at risk of undetected progression to less curable muscle-invasive UC. Studies also suggest a high potential to improve the management of patients with symptoms of primary bladder cancer or during surveillance for detection of recurrence. In general, clinical studies have shown that the positive and negative predictive values of FISH for bladder tumors (pTa-pT4) were 98% and 68%, respectively. Also, the sensitivity of FISH was high (71%-94%) across all histologic grades.

Medicare will consider the Urinary FISH Test medically reasonable and necessary under the following circumstance:

• In the initial diagnosis of persons with hematuria suspected of having bladder carcinoma in conjunction with and not in lieu of current standard diagnostic procedures (this indication is effective for services rendered on or after the FDA-approval date of 01/24/2005)

• Monitoring tumor recurrence in conjunction with cystoscopy in patients previously diagnosed with bladder cancer

• Monitoring for additional recurrence after one or more recurrences have been treated

The Urinary FISH Test for recurrent bladder cancer is not considered medically reasonable and necessary under the following circumstances:

• When performed to provide additional confirmatory information after a diagnosis of bladder cancer recurrence has already been determined and not yet treated

2. The Bladder Tumor Antigen Stat (BTAstat) Test for recurrent bladder cancer is an FDA approved, one-step, qualitative, immunochromatographic assay for the detection of a bladder tumor-associated antigen in voided urine. This antigen is a human complement factor H-related protein (hCFHrp)) similar in composition, structure and function to human complement factor H (hCFH). Like hCFH, the BTA interacting with complement factor C3b interrupts the complement cascade and may confer a selective growth advantage to cancer cells in vivo by allowing the cells to evade the host immune system. In cell culture, hCFHrp is expressed by several bladder cell lines, but not by most normal cells. To interpret the results for the BTAstat test, urine is allowed to react with a colloidal gold-conjugated antibody and the results are determined qualitatively by the presence or absence of a line on the test stick.

The bladder tumor antigen stat test is indicated as an aid in the management of bladder cancer patients in conjunction with cystoscopy. BTAstat test results may be affected by the presence of blood or infection and, therefore, should not be performed on patients exhibiting these signs or symptoms. BTAstat testing has a sensitivity of 68% and a specificity of 71%. The BTAstat test is more sensitive than urine cytology, but not as specific.

Medicare will consider Bladder Tumor Antigen Stat testing medically reasonable and necessary under the following circumstances:

• The patient must have a prior diagnosis of bladder cancer

• The patient is being monitored for a status/recurrence/metastasis of bladder cancer in conjunction with cystoscopy

Bladder Tumor Antigen Stat testing is not considered medically reasonable and necessary under the following circumstances:

• The patient is being screened for an initial diagnosis of bladder cancer

• The patient has signs or symptoms of hematuria or an active infectious/inflammatory condition at the time of the testing (e.g. cystitis, urethritis, or prostatitis)

• The patient has received treatment with Bacillus Calmette-Guerin (BCG).

3. Nuclear matrix is a non-chromatin structure that supports nuclear shape and organizes DNA. It is also involved in DNA replication, transcription and processing of RNA. Nuclear matrix protein 22 (NMP22), a tumor marker, is a nuclear mitotic apparatus protein involved in the distribution of chromatin to daughter cells and is located in the nuclear matrix of all cell types. NMP22 is released from the nuclei of tumor cells after they die and can be detected in the urine. Normally, only very low levels of NMP22 can be detected in the urine, but elevated levels may be associated with bladder cancer.

The NMP-22 Test is an FDA approved in vitro immunoassay intended for the qualitative detection of NMP22 nuclear matrix protein in urine of persons with risk factors or symptoms of bladder cancer or with a history of bladder cancer. This test is indicated for use as an aid in diagnosing and monitoring bladder cancer patients, in conjunction with standard diagnostic procedures.

The Nuclear Matrix Protein 22 Test should not be interpreted as absolute evidence for the presence or absence of bladder cancer. Any disease that could cause nuclear matrix proteins to be present in the urine may cause a positive test result. Positive results have been observed in some patients with benign urological diseases, prostate cancer, and active cancer treatment. NMP-22 tests should not be used for patients with indwelling urinary tract devices (such as stents) or patients who have had a total cystectomy. The results from the Nuclear Matrix Protein 22 test should be used only in conjunction with information available from the clinical evaluation of the patient and other diagnostic procedures. The Nuclear Matrix Protein 22 test has a reported sensitivity of 63%

- 68% and specificity of 68% - 71%.

Medicare will consider Nuclear Matrix Protein 22 (NMP-22) testing medically reasonable and necessary under the following circumstances:

• In the initial diagnosis of persons with symptoms or risk factors for transitional cell cancer (TCC) of the bladder in conjunction with and not in lieu of current standard diagnostic procedures

• In the management of patients with transitional cell carcinoma of the bladder after surgical treatment to identify those patients with occult or rapidly recurring TCC

Nuclear Matrix Protein 22 (NMP-22) testing is not considered medically reasonable and necessary under the following circumstance:

• Testing for NMP-22 as a screening test in the absence of signs and symptoms of illness

Coding Information

Bill Type Codes:

Contractors may specify Bill Types to help providers identify those Bill Types typically used to report this service. Absence of a Bill Type does not guarantee that the policy does not apply to that Bill Type. Complete absence of all Bill Types indicates that coverage is not influenced by Bill Type and the policy should be assumed to apply equally to all claims.

999x Not Applicable

Revenue Codes:

Contractors may specify Revenue Codes to help providers identify those Revenue Codes typically used to report this service. In most instances Revenue Codes are purely advisory; unless specified in the policy services reported under other Revenue Codes are equally subject to this coverage determination. Complete absence of all Revenue Codes indicates that coverage is not influenced by Revenue Code and the policy should be assumed to apply equally to all Revenue Codes.

99999 Not Applicable

CPT/HCPCS Codes

86294 IMMUNOASSAY FOR TUMOR ANTIGEN, QUALITATIVE OR SEMIQUANTITATIVE (EG, BLADDER TUMOR ANTIGEN)

88120 CYTOPATHOLOGY, 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

ICD-9 Codes that Support Medical Necessity XX000 Not Applicable

Diagnoses that Support Medical Necessity N/A

ICD-9 Codes that DO NOT Support Medical Necessity XX000 Not Applicable

ICD-9 Codes that DO NOT Support Medical Necessity Asterisk Explanation

Diagnoses that DO NOT Support Medical Necessity N/A

General Information

Documentations Requirements

Medical record documentation maintained by the ordering physician must clearly indicate the medical necessity of the services being billed. In addition, documentation that the service was performed must be included in the patient’s medical record. This information is normally found in the office/progress notes, hospital notes, and/or test results.

If the provider of the service is other than the ordering/referring physician, that provider must maintain a copy of the documentation of test results and interpretation, along with a copy of the ordering/referring physician’s order for the studies. The physician must state the clinical indication/medical necessity for the study in his order for the test.

Appendices

Utilization Guidelines

It is expected that these services would be performed as indicated by current medical literature and/or standards of practice. When services are performed in excess of established parameters, they may be subject to review for medical necessity.

In general, the monitoring of bladder cancer would be performed by cystoscopy, urine cytology and one urinary tumor marker (e.g., FISH, BTA, or NMP-22) every three months for two years following diagnosis and treatment and twice a year thereafter.

Sources of Information and Basis for Decision

Bubendorf, L., Grilli, B., Sauter, G., Mihatsch, M., Gasser, T., & Dalquen, P. (2001). Multiprobe fish for enhanced detection of bladder cancer in voided urine specimens and bladder washings. Am J Clin Pathol, 116, 79-86.

Reference consulted for clinical trial outcome.

Droller, M. (2002). Current concepts of tumor markers in bladder cancer. Urologic Clinics of North America, Article 12489150 Retrieved August 26, 2003, from http://www.mdconsult.com Reference consulted for an overview of tumor markers and bladder cancer.

Halling, K., King, W., Sokolova, I., Meyer, R., Burkhardt, H., Halling, A., Cheville, J., Sebo, T., Ramakumar, S., Stewart, C., Pankratz, S., O’Kane, D., Seelig, S., Lieber, M., & Jenkins, R. (2000). A comparison of cytology and fluorescence in situ hybridization for the detection of urothelial carcinoma. Journal of Urology, 164(5), 1768- 1775. Source used for comparison of cytology and fluorescence in situ hybridization and clinical trial results.

Pirtskalaishvili, G., Konety, B, & Getzenberg, R. (1999). Update on urine-based markers for bladder cancer. Postgraduate Medicine, 106(6), Article 11. Retrieved August 26, 2003, from http://wwwpostgradmed.com/issues/1999/11_99/pirtskallaishvili.htm Reference consulted for comparison information between tests for tumor markers.

Ponsky, L., Sharma, S., Pandrangi, L., Kedia, S., Nelson, D., Agarwal, A. & Zippe, C. (2001) Screening and monitoring for bladder cancer: Refining the use of NMP22. Journal of Urology, 166(1), 75-78. Reference reviewed for clinical study results.

Poulakis, V., Witzsch, U., DeVries, R., Altmannsberger, H., Manyak, M., & Becht, E. (2001). A comparison of urinary nuclear matrix protein-22 and bladder tumour antigen tests with voided urinary cytology in detecting and following bladder cancer: the prognostic value of false-positive results. BJU International, 88(7), 692-701.

Reference reviewed for clinical study results.

Saad, A., Hanbury, D., McNicholas, T., Boustead, G., Morgan, S., & Woodman, A. (2002). A study comparing various noninvasive methods of detecting bladder cancer in urine. BJU International, 89(4), 369-373. Reference reviewed for clinical study results.

Skacel, M., Fahmy, M., Brainard, J., Pettay, J., Biscotti, C., Liou, L., Procop, G., Jones, J., Ulchaker, J., Zippe, C.,

& Tubbs, R. (2003). Multitarget fluorescence in situ hybridization assay detects transitional cell carcinoma in the majority of patients with bladder cancer and atypical or negative urine cytology. The Journal of Urology. 169, 2101-2105. This source consulted for clinical study results.

Sokolova, I., Halling, K., Jenkins, R., Burkhardt, H., Meyer, R., Seelig, S., & King W. (2000). The development of a multitarget, multicolor fluorescence in situ hybridization assay for the detection of urothelial carcinoma in urine. Journal of Molecular Diagnostics, 2(3), 116-123. This reference consulted for description of FISH test and clinical trial results.

Advisory Committee Meeting Notes This Local Coverage Determination (LCD) does not reflect the sole opinion of the contractor or Contractor Medical Director. Although the final decision rests with the contractor, this LCD was developed in cooperation with advisory groups, which includes representatives from numerous societies.

Start Date of Comment Period

End Date of Comment Period

Start Date of Notice Period 01/01/2011

Revision History Number 1

Revision History Explanation Revision Number1 Start Date of Comment Period:N/A

Start Date of Notice Period:01/01/2011 Revision Effective Date: 01/01/2011

LCR B2011-012

December 2010 Update

Explanation of Revision: Annual 2011 HCPCS Update. Added new codes and descriptors 88120 and 88121 and removed 88367 and 88368 from the “CPT/HCPCS Codes” and “Indication and Limitations of Coverage and/ or Medical Necessity” sections of the LCD. The effective date of this revision is based on date of service.

Revision Number:Original

Start Date of Comment Period:N/A Start Date of Notice Period:12/04/2008 Revised Effective Date:02/02/2009

LCR B2009-

December 2008 Bulletin

This LCD consolidates and replaces all previous policies and publications on this subject by the carrier predecessors of First Coast Service Options, Inc. (Triple S and FCSO).

For Florida (00590) this LCD (L29303) replaces LCD L15079 as the policy in notice. This document (L29303) is effective on 02/02/2009.

11/21/2010 - For the following CPT/HCPCS codes either the short description and/or the long description was changed. Depending on which description is used in this LCD, there may not be any change in how the code displays in the document: 86294 descriptor was changed in Group 1 88367 descriptor was changed in Group 1 88368 descriptor was changed in Group 1

Reason for Change