Serum Tumor Markers in the Management of Malignancies Printer-Friendly Version   

Medical Policy: 02.01.20 
Original Effective Date: December 2000 
Reviewed: December 2007 
Revised: March 2008 

This policy applies to all products unless specific contract limitations, exclusions or exceptions apply. Please refer to the member's coverage manual for benefit availability. Managed care guidelines related to referral authorization, and precertification of inpatient hospitalization, home health, home infusion and hospice services apply.

Description: 

While serum tumor markers can be detected in normal or benign lesions, significant circulating levels are associated with malignancy due to one or more of the following mechanisms:

• Over expression of the antigen by individual malignant cells
• A large tumor burden
• The clearance rate of the marker

Clinical applicability of tumor markers depends upon how their measurements are used to influence the management of the patient.

Policy: 

• Prostate Specific Antigen (PSA) is considered standard of care as a screening test for prostate cancer or follow-up of a patient with prostate disease.
• Serial monitoring of serum levels of carcinoembryonic antigen (CEA) for gastrointestinal malignancies, especially for colorectal cancer.
• Cancer antigen 125 (CA-125) may be considered medically necessary in the following circumstances:
  • In pre-menopausal and peri-menopausal women with a documented complex ovarian mass
  • In post-menopausal women with any documented ovarian mass
  • In patients with gynecologic malignancies, including but not limited to carcinoma of the fallopian tube and endometrial carcinoma:
    • to establish a baseline OR;
    • to monitor disease progression in patients whose baseline levels have been shown to be elevated
• CA 19-9 for patients with an established diagnosis of pancreatic, colorectal, gastric, or biliary cancer, when used to monitor clinical response to therapy.
• CA 15-3 and CA 27.29 for patients with an established diagnosis of breast cancer when used to monitor clinical response to therapy.
• Alpha-fetoprotein (AFP) in the diagnosis, treatment, and identification of residual disease in testicular cancer and hepatocellular carcinoma.
• beta-human Chorionic Gonadotropin (b-hCG) in the diagnosis, treatment, and identification of residual disease in testicular cancer
• Chromogranin A (CgA) to aid in the diagnosis and surveillance of patients with neuroendocrine tumors, including carcinoids

• Measurements of tumor markers CA 72-4, CA 19-9, CA 15-3, CA 27-29, and CA-125 are considered investigational for any indication not listed above, including but not limited to breast and gastrointestinal malignancies.  
• Measurement of CEA for screening of colorectal cancer is considered investigational.
• Measurement of CA-125 for screening for ovarian cancer is considered investigational. 
• Other tumor markers considered investigational include: 

1. CAM-26
2. CAM-29
3. MCA
4. MSA
5. TPA
6. TPS
7. CA-50
8. CA-242
9. CA-195
10. CA-549
11. CA-SCC
12. CAM 17-1
13. CAM-26
14. CAM-29
15. CAR-3
16. DMSA
17. NSE
18. Du-PAN-2
19. MCA
20. TAG-12
21. TAG-72-3
22. TNF-alpha

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Procedure Codes and Billing Guidelines: 

• To report provider services, use appropriate CPT* codes, Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or ICD-9 diagnostic codes.
• The following CPT codes may be used to report serum tumor marker testing:
  • 86300 Immunoassay for tumor antigen, quantitative; CA 15-3 (27.29)
  • 86301 Immunoassay for tumor antigen, quantitative; CA 19-9
  • 86304 Immunoassay for tumor antigen, quantitative; CA 125
  • 86316 Immunoassay for tumor antigen; other antigen, quantitative (eg. CA 50, 72-4, 549, CgA), each
  • 86294 Immunoassay for tumor antigen, qualitative or semiquantitative (eg, bladder tumor antigen).
  • 84153 Prostate specific antigen (PSA); total  

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Selected References: 

• Burtis C.A., Ashwood E.R., editors. Tietz textbook of clinical chemistry. Third edition. Philadelphia: W.B. Saunders, c1999. Pages 735-740.
• Gion M., Boracchi P., Dittadi R., Biganzoli E., Peloso L., Mione R., Gatti C., Paccagnella A., Marubini E. Prognostic role of serum CA 15.3 in 362 node-negative breast cancers. An old player for a new game. European Journal of Cancer; June 2002; 38 (9): 1165-6.
• Jacobs IJ, et al..  Screening for ovarian cancer: a pilot randomised controlled trial.  Lancet  1999 Apr 10;353(9160):1207-10.
• Jacobs IJ, et al.  Risk of diagnosis of ovarian cancer after raised serum CA 125 concentration: a prospective cohort study.  BMJ  1996 Nov 30;313(7069):1355-8.
• ACOG Committee Opinion: number 280, December 2002. The role of the generalist obstetrician-gynecologist in the early detection of ovarian cancer.  Obstet Gynecol  2002 Dec;100(6):1413-6.
• Tuxen MK, Soletormos G, Dombernowsky P. Serum tumor marker CA 125 for monitoring ovarian cancer during follow-up.  Scand J Clin Lab Invest  2002;62(3):177-88.
• Smith RA, Cokkinides V, Eyre HJ et al. American Cancer Society Guidelines for the early detection of cancer, 2003. CA Cancer J Clin 2003 Jan-Feb;53(1):27-43.
• 1995 Technology Evaluation Center (TEC) Assessment; Tab 19: Serum tumor markers for the diagnosis and monitoring of breast cancer.
• 1996 Technology Evaluation Center (TEC) Assessment; Tab 23: Serum tumor markers for the diagnosis and monitoring of gastrointestinal cancer.
• Bast RC, Ravdin P, Hayes D et al. 2000 update of recommendations for the use of tumor markers on breast and colorectal cancer:  clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol 2001; 19(6):1865-78.
• Micke O, Bruns F, Kurowski R et al. Predictive value of carbohydrate antigen 19-9 in pancreatic cancer treated with radiotherapy.  Int J Radiat Oncol Biol Phys 2003; 57(1):90-7.
• Kurebayashi J, Yamaoto Y, Tanaka K et al.  Significance of serum carcinoembryonic antigen and CA 15.3 in monitoring advanced breast cancer patients treated with systemic therapy: a large-scale retrospective study.  Breast Cancer 2003; 10(1):38-44.
• NCCN Hepatobiliary Cancers Panel Members; Benson III AB et al. Hepatocellular Carcinoma. NCCN Clincial Practice Guidelines in Oncology^TM v.1.2006.
• NCCN Testicular Cancer Panel Members; Motzer RJ et al. Testicular Cancer. NCCN Clinical Practice Guidelines in Oncology^TM v.1.2006.
• 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. 2007 Nov 20;25(33):5287-312.
• Zatelli MC, Torta M, Leon A et al. Chromogranin A as a marker of neuroendocrine neoplasia: an Italian Multicenter Study. Endocr Relat Cancer. 2007 Jun;14(2):473-82.
• Seregni E, Ferrari L, Bajetta E et al. Clinical significance of blood chromogranin A measurement in neuroendocrine tumours. Ann Oncol. 2001;12 Suppl 2:S69-72.
• Stirling D, Evans DGR, Pichert G et al. Screening for Familial Ovarian Cancer: Failure of Current Protocols to Detect Ovarian Cancer at an Early Stage According to the International Federation of Gynecology and Obstetrics System. J Clin Oncol 2005; 23(24):5588-5596.
• Bast Jr. RC. Status of Tumor Markers in Ovarian Cancer Screening. J Clin Oncol 2003; 21(10s):200s-205s.
• Karlan BY, McIntosh M. The Quest for Ovarian Cancer’s Holy Grail: Can CA-125 Still Be the Chalice of Early Detection? J Clin Oncol 2007;25(11): 1303-1304.  

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Wellmark Blue Cross and Blue Shield
Medical Policy Analyst
Station 304
636 Grand Ave
Des Moines, Iowa 50309

*Current Procedural Terminology © 2008 American Medical Association. All Rights Reserved.

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 partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.