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Medical Policy Serum Tumor Markers for Breast and Gastrointestinal Malignancies Table of Contents • Policy: Commercial • Coding Information
• Information Pertaining to All Policies
• Policy: Medicare • Description
• References
• Authorization Information • Policy History
• Endnotes Policy Number: 538 BCBSA Reference Number: 2.03.02A (For Plan internal use only) Related Policies
Non-BRCA Breast Cancer Risk Assessment (eg, OncoVue) #188 Tumor Markers for Diagnosis and Management of Cancer #167

Policy1 Commercial Members: Managed Care (HMO and POS), PPO, and Indemnity

CA 15-3 (also known as CA 27-29, Truquant BR RIA®) This testing is used to monitor women for breast cancer. Experts disagree about whether this test gives valuable information to breast cancer patients.
Therefore, we have chosen to let doctors and patients make their own informed decisions about this test.

CA 19-9 testing for patients with an established diagnosis of pancreatic cancer or gastric cancer may be considered MEDICALLY NECESSARY when used to monitor the clinical response to therapy in order to either discontinue ineffective therapy or to detect early recurrence of disease.

CA 19-9 testing for the diagnosis, following, or prognosis of colorectal, liver or breast cancer is considered INVESTIGATIONAL.

CEA testing for the diagnosis and follow-up of metastatic breast cancer and for gastrointestinal malignancies may be considered MEDICALLY NECESSARY.

CEA testing for the diagnosis, following, or prognosis of lung cancer is considered INVESTIGATIONAL.

CEA testing for routine cancer screening is considered INVESTIGATIONAL.

Prior Authorization Information
Inpatient • For services described in this policy, precertification/preauthorization IS REQUIRED for all products if the procedure is performed inpatient.
Outpatient • For services described in this policy, see below for products where prior authorization might be required if the procedure is performed outpatient.

Outpatient

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  Commercial Managed Care (HMO and POS) Prior authorization is not required. Commercial PPO and Indemnity Prior authorization is not required.

  CPT Codes / HCPCS Codes / ICD Codes
  Inclusion or exclusion of a code does not constitute or imply member coverage or provider reimbursement. Please refer to the member’s contract benefits in effect at the time of service to determine coverage or non- coverage as it applies to an individual member.

  Providers should report all services using the most up-to-date industry-standard procedure, revenue, and diagnosis codes, including modifiers where applicable.

  The following codes are included below for informational purposes only; this is not an all-inclusive list.

  The above medical necessity criteria MUST be met for the following codes to be covered for Commercial Members: Managed Care (HMO and POS), PPO, and Indemnity: CPT Codes CPT codes: Code Description 82378 Carcinoembryonic antigen (CEA) The following ICD Diagnosis Codes are considered medically necessary when submitted with the CPT code above if medical necessity criteria are met: ICD-10 Diagnosis Codes ICD-10-CM diagnosis codes: Code Description C15.3 Malignant neoplasm of upper third of esophagus C15.4 Malignant neoplasm of middle third of esophagus C15.5 Malignant neoplasm of lower third of esophagus C15.8 Malignant neoplasm of overlapping sites of esophagus C15.9 Malignant neoplasm of esophagus, unspecified C16.0 Malignant neoplasm of cardia C16.1 Malignant neoplasm of fundus of stomach C16.2 Malignant neoplasm of body of stomach C16.3 Malignant neoplasm of pyloric antrum C16.4 Malignant neoplasm of pylorus C16.5 Malignant neoplasm of lesser curvature of stomach, unspecified C16.6 Malignant neoplasm of greater curvature of stomach, unspecified C16.8 Malignant neoplasm of overlapping sites of stomach C16.9 Malignant neoplasm of stomach, unspecified C17.0 Malignant neoplasm of duodenum C17.1 Malignant neoplasm of jejunum C17.2 Malignant neoplasm of ileum C17.3 Meckel's diverticulum, malignant C17.8 Malignant neoplasm of overlapping sites of small intestine C17.9 Malignant neoplasm of small intestine, unspecified C18.0 Malignant neoplasm of cecum C18.1 Malignant neoplasm of appendix C18.2 Malignant neoplasm of ascending colon C18.3 Malignant neoplasm of hepatic flexure C18.4 Malignant neoplasm of transverse colon C18.5 Malignant neoplasm of splenic flexure C18.6 Malignant neoplasm of descending colon

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  C18.7 Malignant neoplasm of sigmoid colon C18.8 Malignant neoplasm of overlapping sites of colon C18.9 Malignant neoplasm of colon, unspecified C19 Malignant neoplasm of rectosigmoid junction C20 Malignant neoplasm of rectum C21.0 Malignant neoplasm of anus, unspecified C21.1 Malignant neoplasm of anal canal C21.2 Malignant neoplasm of cloacogenic zone
  C21.8 Malignant neoplasm of overlapping sites of rectum, anus and anal canal C25.0 Malignant neoplasm of head of pancreas C25.1 Malignant neoplasm of body of pancreas C25.2 Malignant neoplasm of tail of pancreas C25.3 Malignant neoplasm of pancreatic duct C25.4 Malignant neoplasm of endocrine pancreas C25.7 Malignant neoplasm of other parts of pancreas C25.8 Malignant neoplasm of overlapping sites of pancreas C25.9 Malignant neoplasm of pancreas, unspecified C26.0 Malignant neoplasm of intestinal tract, part unspecified C26.9 Malignant neoplasm of ill-defined sites within the digestive system C50.011 Malignant neoplasm of nipple and areola, right female breast C50.012 Malignant neoplasm of nipple and areola, left female breast C50.019 Malignant neoplasm of nipple and areola, unspecified female breast C50.021 Malignant neoplasm of nipple and areola, right male breast C50.022 Malignant neoplasm of nipple and areola, left male breast C50.029 Malignant neoplasm of nipple and areola, unspecified male breast C50.111 Malignant neoplasm of central portion of right female breast C50.112 Malignant neoplasm of central portion of left female breast C50.119 Malignant neoplasm of central portion of unspecified female breast C50.121 Malignant neoplasm of central portion of right male breast C50.122 Malignant neoplasm of central portion of left male breast C50.129 Malignant neoplasm of central portion of unspecified male breast C50.211 Malignant neoplasm of upper-inner quadrant of right female breast C50.212 Malignant neoplasm of upper-inner quadrant of left female breast C50.219 Malignant neoplasm of central portion of unspecified male breast C50.311 Malignant neoplasm of lower-inner quadrant of right female breast C50.312 Malignant neoplasm of lower-inner quadrant of left female breast C50.319 Malignant neoplasm of lower-inner quadrant of unspecified female breast C50.321 Malignant neoplasm of lower-inner quadrant of right male breast C50.322 Malignant neoplasm of lower-inner quadrant of left male breast C50.329 Malignant neoplasm of lower-inner quadrant of unspecified male breast C50.411 Malignant neoplasm of upper-outer quadrant of right female breast C50.412 Malignant neoplasm of upper-outer quadrant of left female breast C50.419 Malignant neoplasm of upper-outer quadrant of unspecified female breast C50.421 Malignant neoplasm of upper-outer quadrant of right male breast C50.422 Malignant neoplasm of upper-outer quadrant of left male breast C50.429 Malignant neoplasm of upper-outer quadrant of unspecified male breast C50.511 Malignant neoplasm of lower-outer quadrant of right female breast C50.512 Malignant neoplasm of lower-outer quadrant of left female breast C50.519 Malignant neoplasm of lower-outer quadrant of unspecified female breast C50.521 Malignant neoplasm of lower-outer quadrant of right male breast C50.522 Malignant neoplasm of lower-outer quadrant of left male breast C50.529 Malignant neoplasm of lower-outer quadrant of unspecified male breast

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  C50.611 Malignant neoplasm of axillary tail of right female breast C50.612 Malignant neoplasm of axillary tail of left female breast C50.619 Malignant neoplasm of axillary tail of unspecified female breast C50.621 Malignant neoplasm of axillary tail of right male breast C50.622 Malignant neoplasm of axillary tail of left male breast C50.629 Malignant neoplasm of axillary tail of unspecified male breast C50.811 Malignant neoplasm of overlapping sites of right female breast C50.812 Malignant neoplasm of overlapping sites of left female breast C50.819 Malignant neoplasm of overlapping sites of unspecified female breast C50.821 Malignant neoplasm of overlapping sites of right male breast C50.822 Malignant neoplasm of overlapping sites of left male breast C50.829 Malignant neoplasm of overlapping sites of unspecified male breast C50.911 Malignant neoplasm of unspecified site of right female breast C50.912 Malignant neoplasm of unspecified site of left female breast C50.919 Malignant neoplasm of unspecified site of unspecified female breast C50.921 Malignant neoplasm of unspecified site of right male breast C50.922 Malignant neoplasm of unspecified site of left male breast C50.929 Malignant neoplasm of unspecified site of unspecified male breast C50.A0 Malignant inflammatory neoplasm of unspecified breast C50.A1 Malignant inflammatory neoplasm of right breast C50.A2 Malignant inflammatory neoplasm of left breast C78.4 Secondary malignant neoplasm of small intestine C78.5 Secondary malignant neoplasm of large intestine and rectum C78.7 Secondary malignant neoplasm of liver and intrahepatic bile duct C78.89 Secondary malignant neoplasm of other digestive organs C79.2 Secondary malignant neoplasm of skin C79.81 Secondary malignant neoplasm of breast D01.0 Carcinoma in situ of colon D01.1 Carcinoma in situ of rectosigmoid junction D01.2 Carcinoma in situ of rectum D05.90 Unspecified type of carcinoma in situ of unspecified breast D05.91 Unspecified type of carcinoma in situ of right breast D05.92 Unspecified type of carcinoma in situ of left breast D37.1 Neoplasm of uncertain behavior of stomach D37.2 Neoplasm of uncertain behavior of small intestine D37.4 Neoplasm of uncertain behavior of colon D37.5 Neoplasm of uncertain behavior of rectum D48.60 Neoplasm of uncertain behavior of unspecified breast D48.61 Neoplasm of uncertain behavior of right breast D48.62 Neoplasm of uncertain behavior of left breast D49.3 Neoplasm of unspecified behavior of bladder Z85.028 Neoplasm of unspecified behavior of bladder Z85.038 Personal history of other malignant neoplasm of large intestine Z85.048 Personal history of other malignant neoplasm of rectum, rectosigmoid junction, and anus

  The above medical necessity criteria MUST be met for the following codes to be covered for Commercial Members: Managed Care (HMO and POS), PPO, and Indemnity: CPT Codes CPT codes: Code Description 86301 Immunoassay for tumor antigen, quantitative; CA 19-9

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  The following ICD Diagnosis Codes are considered medically necessary when submitted with the CPT code above if medical necessity criteria are met: ICD-10 Diagnosis Codes ICD-10-CM diagnosis codes: Code Description C16.0 Malignant Neoplasm of Cardia C16.1 Malignant Neoplasm of Fundus of Stomach C16.2 Malignant Neoplasm of Body of Stomach C16.3 Malignant Neoplasm of Pyloric Antrum C16.4 Malignant Neoplasm of Pylorus C16.5 Malignant Neoplasm of Lesser Curvature of Stomach, Unspecified C16.6 Malignant Neoplasm of Greater Curvature of Stomach, Unspecified C16.8 Malignant Neoplasm of Overlapping Sites of Stomach C16.9 Malignant Neoplasm of Stomach, Unspecified C25.0 Malignant Neoplasm of Head of Pancreas C25.1 Malignant Neoplasm of Body of Pancreas C25.2 Malignant Neoplasm of Tail of Pancreas C25.3 Malignant Neoplasm of Pancreatic Duct C25.7 Malignant Neoplasm of Other Parts Of Pancreas C25.8 Malignant Neoplasm of Overlapping Sites of Pancreas C25.9 Malignant Neoplasm of Pancreas, Unspecified C78.7 Secondary Malignant Neoplasm of Liver and Intrahepatic Bile Duct C78.80 Secondary Malignant Neoplasm of Unspecified Digestive Organ C78.89 Secondary Malignant Neoplasm of Other Digestive Organs D00.2 Carcinoma in Situ of Stomach D01.7 Carcinoma in Situ of Other Specified Digestive Organs D01.9 Carcinoma in Situ of Digestive Organ, Unspecified

  The above medical necessity criteria MUST be met for the following codes to be covered for Commercial Members: Managed Care (HMO and POS), PPO, and Indemnity: CPT Codes CPT codes: Code Description 86300 Immunoassay for tumor antigen, quantitative; CA 15-3 (27.29) Description Serum tumor markers are molecules or substances shed by a tumor into the circulation where they can be detected and quantitated. Noncirculating tumor markers include those that can be detected histochemically or cytogenetically on a tissue sample. Examples of the latter include the HER2 oncoprotein, detected by immunohistochemistry on a subset of breast cancers, and the Philadelphia chromosome, which is a cytogenetic marker for chronic myelogenous leukemia.

  Serum tumor markers have been investigated in many malignancies, including most prominently myeloma (ie, 2-microglobulin), germ cell tumors (ie, alpha fetoprotein, human chorionic gonadotropin), and prostate cancer (ie, PSA). The HER2 oncoprotein extracellular domain has been studied as a serum tumor marker in breast and other malignancies. Carcinoembryonic antigen (CEA) has also been widely investigated in gastrointestinal malignancies. This policy focuses on specific tumor markers for breast and gastrointestinal malignancies.

  For breast cancer, the most extensively investigated serum tumor markers besides HER2 are those associated with the MUC-1 gene. For gastrointestinal cancer, including gastric, pancreatic, and colorectal cancer, the most extensively studied tumor markers, other than CEA, are those related to mucinous glycoproteins. The MUC-1 gene encodes a cell-associated mucin-like antigen, and different antibodies may be used to detect different epitopes. CA 15-3 and CA 27.29 are 2 related monoclonal antibodies that detect epitopes encoded by the

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  MUC-1 gene. While much of the literature has focused on the use of CA 15-3, it has been largely replaced by CA 27.29, which is reportedly more sensitive. The mucinous glycoproteins of the gastrointestinal tract include CA 19-9, and CA 72-4, depending on which antibody is used.

  Since serum tumor markers can also be detected in normal or benign lesions, significantly elevated circulating levels may occur with malignancy by one or more of the following mechanisms: (1) overexpression of the antigen by malignant cells; (2) a large tumor burden; and/or (3) slower clearance of the marker. For example, since most tumor markers are cleared by the liver, liver abnormalities (whether benign, malignant, or inflammatory) may elevate tumor marker concentrations due to impaired clearance. Because most tumor markers are not unique to malignancy, cut-off points must be established for normal versus abnormal marker levels. In contrast, serial monitoring of serum tumor markers in a setting of established malignancy may not require such cutoff points. Various clinical applications of serum tumor markers can be broadly divided into 2 categories, those involving a single measurement and those involving serial measurements.
  Policy History Date Action 10/2025 Clarified coding information. 3/2024 Prior authorization information clarified. Prior authorization is not required. 11/2022 Annual policy review. Policy updated with literature review through October 2022. No references added. Policy statements unchanged. 1/2021 Medicare information removed. See MP #132 Medicare Advantage Management for local coverage determination and national coverage determination reference.
  6/2019 Clarified coding information. 2/2016 Clarified coding information. 11/2015 Ongoing medically necessary and investigational statements transferred from medical policy #167 Tumor Markers for Diagnosis and Management of Cancer. 11/1/2015 1/2015 Clarified coding information. 6/2014 Updated coding section with ICD10 procedure and diagnosis codes, effective 10/2015.
  4/2014 Clarified coding information.
  6/2012 Annual policy review. New references added. Information Pertaining to All Blue Cross Blue Shield Medical Policies Click on any of the following terms to access the relevant information: Medical Policy Terms of Use Managed Care Guidelines Indemnity/PPO Guidelines Clinical Exception Process Medical Technology Assessment Guidelines

  References

  1. 1995 TEC Assessments; Tab 19: Serum tumor markers for the diagnosis and monitoring of breast cancer.
  2. 1996 TEC Assessments; Tab 23: Serum tumor markers for the diagnosis and monitoring of gastrointestinal cancer.
  3. 1996 TEC Assessments; Tab 24: Serum tumor markers (CA 15-3, CA 27.29 and CA 549) for the monitoring of breast cancer recurrence.
  4. Locker GY, Hamilton S, Harris J et al. ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. J Clin Oncol 2006; 24(33):5313-27.
  5. 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; 25:5287-5312.
  6. Rosselli Del Turco, M, Palli D, Cariddi A et al. Intensive diagnostic follow-up after treatment of primary breast cancer. A randomized trial. JAMA 1994; 271(20):1593-7.
  7. The GIVIO Investigators. Impact of follow-up testing on survival and health-related quality of life in breast cancer patients. A multicenter randomized controlled trial. JAMA 1994; 271(20):1587-92.
  8. Kokko R, Holli K, Hakama M. CA 15-3 in the follow-up of localised breast cancer; a prospective study. Eur J Cancer 2002; 38(9):1189-93.

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  9. Kurebayashi J, Yamamoto 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.
  10. Ebeling FG, Stieber P, Untch M et al. Serum CEA and CA 15-3 as prognostic factors in primary breast cancer. Br J Cancer 2002; 86(8):1217-22.
  11. Gion M, Boracchi P, Dittadi R et al. Prognostic role of serum CA 15.3 in 362 node-negative breast cancers. An old player for a new game. Eur J Cancer 2002; 38(9):1181-8.
  12. Duffy MJ, Evoy D, McDermott EW. CA 15-3: Uses and limitation as a biomarker for breast cancer. Clin Chim Acta 2010; 411:1869-74.
  13. Rocha Lima CM, Savarese D, Bruckner H et al. Irinotecan plus gemcitabine induces both radiographic and CA 19-9 tumor marker responses in patients with previously untreated advanced pancreatic cancer. J Clin Oncol 2002; 20(5):1182-91.
  14. Micke O, Bruns F, Kurowski R, et al. Predictive value of carbohydrate antigen 19-9 in pancreatic cancer treated with radiochemotherapy. Int J Radiat Oncol Biol Phys 2003; 57(1):90-7
  15. Katz A, Hanlon A, Lanciano R et al. Prognostic value of CA 19-9 levels in patients with carcinoma of the pancreas treated with radiotherapy. Int J Radiat Oncol Biol Phys 1998; 41(2):393-6
  16. Ohara K, Tatsuzaki H, Molotkova NG et al. Utility of serum CA 19-9 monitoring in preoperative radiotherapy for pancreatic cancer. Hepatogastroenterology 2001; 48(39):859-63.
  17. Ziske C, Schlie C, Gorschluter M et al. Prognostic value of CA 19-9 levels in patients with inoperable adenocarcinoma of the pancreas treated with gemcitabine. Br J Cancer 2003; 89(8):1413-7.
  18. Duffy MJ, Sturgeon C, Lamerz R, et al. Tumor markers in pancreatic cancer: a European Group on Tumor Markers (EGTM) status report. Ann Oncol 2010; 21:441-7.
  19. Berger AC, Garcia Jr M, Hoffman JP, et al. Postresection CA 19-9 predicts overall survival in patients with pancreatic cancer treated with adjuvant chemoradiation: A prospective validation by RTOG 9704. J Clin Oncol 2008; 26:5918-22.
  20. Hess V, Glimelius B, Grawe P, et al. CA 19-9 tumour-marker response to chemotherapy in patients with advanced pancreatic cancer enrolled in a randomized controlled trial. Lancet Oncol 2008; 9(2):132-8.

  Endnotes

  1 Based on expert opinion