The following tumor markers are eligible for payment when medically necessary and should be processed as follows:

• Prostate specific antigen (PSA); total - 84153
• Prostate specific antigen (PSA); free - 84154
• Prostate specific antigen (PSA); complexed (direct method) - 84152
• Immunoassay for prostate specific antigen (PSA); asymptomatic patient - G0103
  Note: Only covered by certain groups or programs as indicated in the benefit schedule.
• Alpha-fetoprotein (AFP); serum - 82105, 82107 
• Carcinoembryonic antigen (CEA) - 82378
• Immunoassay for tumor antigens:

CA 125 (86304)
CA 125 is payable when reported for patients with symptoms suggestive of ovarian cancer or in those with known ovarian cancer (183.0, 198.6, 233.30, 233.39, V10.43).  It is also payable for patients with carcinomas of the fallopian tube, endometrium, endocervix and may be associated with the presence of a malignant mesothelioma (180.0, 182.0, 183.2, 183.8, 184.8, 198.82, 236.0-236.3, V10.42, V10.43), as well as primary peritoneal carcinoma and metastatic adeno cancer of unknown origin in the peritoneum (158.0-158.9, 197.6). 

CA 27.29 or CA 15-3 (86300)
CA 27.29 or CA 15-3 are payable when reported for use in the management of patients with breast cancer (174.0-174.9, 175.0-175.9, 198.2, 198.81, V10.3).

CA 19-9 (86301)
CA 19-9 is payable when reported for monitoring response to treatment in patients with an established diagnosis of pancreatic and biliary ductal carcinoma (155.1, 156.1, 156.8, 156.9, 157.0-157.9, 197.8, 230.9, 235.3, 235.5, V10.09). This test is not indicated for making the diagnosis of pancreatic or biliary cancer.

BTA  or NMP-22 (86294)
Bladder Tumor Antigen (BTA) or nuclear matrix protein 22 (NMP-22) are payable when reported as an adjunct to cystoscopy in the diagnosis of bladder cancer and to monitor for eradication of the cancer, or recurrences after eradication (188.0-188.9, 198.1, 233.7, 239.4, V10.51).

For patients presenting with signs and symptoms (596.7, 596.8, 599.70-599.72, 788.1, 788.41-788.43, 788.63, 788.69, 788.91-788.99) suspicious of bladder cancer, payment may be made for BTA or NMP-22 in conjunction with cystoscopy to "rule out" bladder cancer.

There is insufficient scientific evidence to determine the efficacy of CA 125, CA 27.29, CA 15-3, CA 19-9, BTA and NMP-22 in the clinical management of malignancies other than those listed above. Therefore, when reported for cancer diagnoses other than those listed above, these tumor markers are considered experimental/investigational and not covered. A participating, preferred, or network provider can bill the member for the test. In addition, when performed for patients with non-malignant diagnoses, tumor marker testing is considered not medically necessary and not covered. Effective January 26, 2009, a participating, preferred or network provider cannot bill the member for the denied service unless the provider has given advance written notice, informing the member that the service may be deemed not medically necessary and providing an estimate of the cost.  The member must agree in writing to assume financial responsibility, in advance of receiving the service.  The signed agreement should be maintained in the provider's records. When performed for asymptomatic patients, tumor marker testing is considered screening and only covered by certain groups or programs as indicated in benefits.

CA 125, CA 27.29, CA 15-3,  and CA 19-9 are not indicated for diagnosing. Therefore, no payment should be made to "rule out" the covered diagnoses for these markers.

NOTE:

Code 86316 (Immunoassay for tumor antigen; other antigen, quantitative) represents immunoassays for tumor antigens not designated with a specific procedure code. When reported, code 86316 will be denied as experimental/investigational for cancer diagnoses and will be denied as noncovered for any nonmalignant diagnosis. In addition, when performed for asymptomatic patients, tumor markers reported under code 86316 are considered screening and only covered by certain groups or programs as indicated in benefits.

The use of fluorescence in situ hybridization (FISH) (88365) is payable when reported as an adjunct to cystoscopy in the diagnosis (in persons with hematuria suspected of having bladder cancer) and monitoring of bladder cancer (188.0-188.9, 198.1, 233.7, 239.4, 599.70-599.72, V10.51).

The use of the ImmunoCyt test (88346) is payable when reported as an adjunct to cytology and cystoscopy to monitor for bladder cancer recurrence (188.0-188.9, 198.1, 233.7, 239.4, V10.51).

Date Last Reviewed: 06/2009

Circulating Tumor Cells Testing

The detection and quantification of circulating tumor cells (S3711) is considered experimental/investigational in the management of patients with cancer.  There is insufficient evidence that this technology is equal to or better than any existing tumor markers in its efficacy and clinical utility.  It has not been demonstrated that overall health outcomes are affected for patients with metastatic cancer.  A participating, preferred, or network provider can bill the member for the denied test.

Date Last Reviewed: 01/2009

Description

Radioimmunoassay and immunohistochemical determination of the serum levels of certain proteins or carbohydrates have been developed as "markers" for various cancers. Normal cells express these chemicals in low quantities. Tumor size and grade are believed to be reflected by significant elevations in serum concentration of these markers. The uses of tumor marker testing include screening, diagnosis and monitoring response to treatment.

Fluorescence In Situ Hybridization (FISH) is a molecular cytogenetic test used to investigate chromosomal abnormalities associated with cancer and genetic disorders. The major difference between the FISH test and the immunoassay tests is that they detect different substances and use different detection methods. FISH DNA probe technology is a technique to visualize nucleic acid sequences within cells by creating short sequences of fluorescently labeled, single-stranded DNA called probes, that match target sequences. The probes bind to complementary strands of DNA, allowing for identification of the locations of the chromosomes targeted.

The ImmunoCyt test uses fluorescence immunohistochemistry using antibodies to mucin glycoprotein and a carcinoembryonic antigen (CEA).  These antigens are found on bladder tumor cells.  This test is intended to augment the sensitivity of cytology for the detection of tumor cells in the urine of individuals previously diagnosed with bladder cancer.  It is indicated for use in conjunction with cytoscopy as an aid in the management of bladder cancer.

Circulating Tumor Cells Testing

Studies have suggested that the presence of circulating tumor cells in patients with metastatic carcinoma is associated with short survival.  Detecting and quantifying circulating tumor cells may be useful in providing an immediate assessment of response to chemotherapy rather than relying on changes in imaging studies (i.e., computed tomography scans).  In addition, the presence of circulating tumor cells has been investigated as an additional prognostic factor in women with breast cancer without metastases, which could be used to determine the need for additional adjuvant chemotherapy.  The CellSearch™ System (Veridex) is an example of such a technology.  The technique involves identification of the circulating tumor cells, which are tagged using antibody-coated magnetic beads that recognize cell surface antigens.  The cells are then labeled with fluorescent dyes, which can then be quantified by a semiautomated fluorescent-based microscopy system. 

NOTE:

This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical circumstances may warrant individual consideration, based on review of applicable medical records.

This medical policy may not apply to FEP.  Medial policy is not an authorization, certification, explanation of benefits or a contract.  Benefits are determined by the Federal Employee Program.

National Blue Cross Blue Shield Association Medical Policy 2.04.07, Urinary Tumor Markers for Bladder Cancer, 4:2006

Reporting Recommendations for Tumor Marker Prognostic Studies (Remark), Breast Cancer Res Treat, Volume 100, No. 2, 11/2006

ASCO Practice Guidelines on Breast Cancer Follow-Up and Management in the Adjuvant Setting, Journal of Clinical Oncology, Volume 24, No. 31, 11/2006

ASCO Recommendations for the Use of Tumor Markers in Gastrointestinal Cancer, Journal of Clinical Oncology, Volume 24, No. 33, 11/2006

Diagnostic Utility of the ImmunoCyt/uCyt+ Test in Bladder Cancer, Rev Urol, Volume 8, No. 4, Fall/2006

Performance of Urine Test in Patients Monitored for Recurrence of Bladder Cancer: A Multicenter Study in the United States, J Urol, Volume 174, No. 4Pt1, 10/2005

Borglum T, Rehfeld J, Drivsholm L, Hilsted L. Processing-Independent Quantitation of Chromogranin A in Plasma from Patients with Neuroendocrine Tumors and Small-Cell Lung Carcinomas. Clinical Chemistry. March 2007;53(3):438-446.

Harris L, Fritsche H, Mennel R, et. al. American Society of Clinical Oncology 2007 Update of Recommendations for the Use of Tumor Markers in Breast Cancer. J Clin Oncol. November 20, 2007;25(33). Accessed May 12, 2009.

Goral V, Yesilbagdan H, Kaplan A, Sit D. Evaluation of CA 72-4 as a New Tumor Marker in Patients with Gastric Cancer. Hetapo-Gastroenterology. 2007;54:1272-1275.

Sturgeon C, Duffy M, Stenman U, et. al. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for Use of Tumor Markers in Testicular, Prostate, Colorectal, Breast and Ovarian Cancers. Clinical Chemistry. 2008;54(12):e11-e79.

Nossov V, Amneus M, Su F. The early detection of ovarian cancer: from traditional methods to proteomics. Can we really do better than serum CA-125? American Journal of Obstetrics and Gynecology. September 2008;199(3). Accessed May 22, 2009.

Ramirez M, Nelson E, Evans C. Beyond Prostate-Specific Antigen: Alternate Serum Markers. Prostate Cancer Prostatic Dis. 2008;11(3). Accessed September 24, 2008.

Papadopoulos G, Iordanidou L, Stathouros G, et. al. Evaluation of Urine Tumor-Associated Trypsin Inhibitor, CYFRA 21-1, and Urinary Bladder Cancer Antigen for Detection of High-Grade Bladder Carcinoma. Urology. November 2008;72(5). 

Amonkar S, Bertenshaw G, Chen T-H.et. al. Development and Preliminary Evaluation of a Multivariate Index Assay for Ovarian Cancer. Ovarian Cancer Assay. February 2009;4(2). Accessed May 22, 2009.

Zhu Z-H, Sun B-Y, Ma Y, et. al. Three Immunomarker Support Vector Machines-Based Prognostic Classifiers for Stage IB Non-Small-Cell Lung Cancer. J Clin Oncol. March 1, 2009;27(7).

American Cancer Society. Tumor Markers. The American Cancer Society. www.cancer.org. Accessed May 12, 2009.

American Society of Clinical Oncology. 2006 Update of ASCO Recommendations for the Use of Tumor Markers in Gastrointestinal Cancer. Journal of Oncology Practice;2(6). www.jop.ascopubs.org. Accessed May 11, 2009.

National Comprehensive Cancer Network. Early Detection Key in Ovarian Cancer. www.nccs.com/Making-Treatment-Decisions. Accessed June 2, 2009.

The National Academy of Clinical Biochemistry. Laboratory Medicine Practice Guidelines: Use of Tumor Markers in Clinical Practice Quality Requirements. www.aacc.org/members/nacb/LMPG/OnlineGuide/PublishedGuidelines/tumor/Documents/TumorMarkers2008 Accessed June 8, 2009.

BC Cancer Agency. Cancer Management Guidelines – Neuroendocrine. www.bccancer.bc.ca/nr/bcca/asp. Accessed June 8, 2009.