BlueCross BlueShield of Tennessee Medical Policy Manual

Serum Tumor Markers for Gastrointestinal Cancer

DESCRIPTION

Serum tumor markers are substances produced by cells in response to cancer or certain noncancerous conditions. Most tumor markers are made by normal cells as well as cancer cells; however, they are produced at much higher levels in cancerous conditions.  Carcinoembryonic antigen (CEA) testing is appropriate as part of the pre-surgical workup and as a surveillance tool for colon and rectal cancers.

CA 19-9 is the best-validated and most clinically useful biomarker for early detection and surveillance of pancreatic cancer. CA 19-9 is commonly expressed and shed in pancreatic and hepatobiliary disease and in many malignancies; thus, it is not tumor specific. However, the degree of increase in levels may be useful in differentiating pancreatic adenocarcinoma from inflammatory conditions of the pancreas. CA 19-9 has potential uses in diagnosis, staging, and determining resectability, as a prognostic marker after resection and as a predictive marker for response to chemotherapy. 

Note: Other biomarker tests that require urine, stool, tumor fluid aspirate or tumor tissue samples (e.g., PancraGEN™) are outside the scope of this policy.

POLICY

MEDICAL APPROPRIATENESS

IMPORTANT REMINDERS

ADDITIONAL INFORMATION 

Current data are insufficient to recommend additional biomarkers, such as CA 72 and CA 125 for screening, diagnosis, staging, surveillance or monitoring treatment of individuals with colorectal cancer.  CA 19-9’s low positive predictive value makes it a poor biomarker for pancreatic cancer screening.

SOURCES  

American Society of Clinical Oncology. (2006). Update of recommendations for the use of tumor markers in gastrointestinal cancer. Retrieved August 9, 2016 from www.jco.ascopubs.org.

Ballehaninna, U.K., & Chamberlain, R.S. (2012). The clinical utility of serum CA 19-9 in the diagnosis, prognosis and management of pancreatic adenocarcinoma: an evidence based appraisal. Journal of Gastrointestinal Oncology, 3 (2), 105-119. DOI:10.3978/j.issn.2078-6891.2011.021. (Level 2 evidence)

Bauer, T., El-Rayes, B., Li, X., Hammad, N., Philip, P., Shields, A., et al. (2013). Carbohydrate antigen 19-9 is a prognostic and predictive biomarker in patients with advanced pancreatic cancer who receive gemcitabine-containing chemotherapy: a pooled analysis of 6 prospective trials. Cancer, 119 (2), 285-292. (Level 2 evidence)

Centers for Medicare & Medicaid Services. CMS.gov. National Coverage Determination (NCD) for carcinoembryonic antigen (190.26). Retrieved September 29, 2015 from https://www.cms.gov.

Centers for Medicare & Medicaid Services. CMS.gov. National Coverage Determination (NCD) for tumor antigen by immunoassay – CA 19-9 (190.30). Retrieved September 29, 2015 from https://www.cms.gov.

Huang, Z., & Liu, F. (2014). Diagnostic value of serum carbohydrate antigen 19-9 in pancreatic cancer: a meta-analysis. Tomour Biology, 35 (8), 7459-7465. Abstract retrieved August 26, 2016 from PubMed database.

Humphris, J., Chang, D., Johns, A., Scarlett, C., Pajic, M., Jones, M., et al. (2012). The prognostic and predictive value of serum CA19.9 in pancreatic cancer. Annals of Oncology, 23, 1713-1722. (Level 2 evidence)

National Comprehensive Cancer Network. (2019, November). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Pancreatic adenocarcinoma. Version 1.2020. Retrieved August 13, 2020 from the National Comprehensive Cancer Network.

National Comprehensive Cancer Network. (2020, August). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Hepatobiliary cancers. Version 5.2020. Retrieved August 13, 2020 from the National Comprehensive Cancer Network.

National Comprehensive Cancer Network. (2020, July). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Esophageal and esophagogastric junction cancers. Version 3.2020. Retrieved August 13, 2020 from the National Comprehensive Cancer Network.

National Comprehensive Cancer Network. (2020, June). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Colon cancer. Version 4.2020. Retrieved August 13, 2020 from the National Comprehensive Cancer Network.

National Comprehensive Cancer Network. (2020, June). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Rectal cancer. Version 6.2020. Retrieved August 13, 2020 from the National Comprehensive Cancer Network.

Osayi, S., Bloomston, M., Schmidt, C., Ellison, E., & Muscarella, P. (2014). Biomarkers as predictors of recurrence following curative resection for pancreatic ductal adenocarcinoma: a review. Biomed Research International, 2014:468959. Doi: 10.1155/2014/468959. Epub 2014 Jun 24.  (Level 2 evidence)

Primrose, J., Perera, R., Gray, A., Rose, P., Fuller, A., Corkhill, A., et al. (2014). Effect of 3 to 5 years of scheduled CEA and CT follow-up to detect recurrence of colorectal cancer: the FACS randomized clinical trial. Journal of American Medical Association, 311 (3), 263-270. (Level 2 evidence)

Sorensen, C., Karisson, W., Pommergaard, H., Burcharth, J., & Rosenberg, J. (2016). The diagnostic accuracy of carcinoembryonic antigen to detect colorectal cancer recurrence – a systematic review. International Journal of Surgery, 25, 134-144. Abstract retrieved August 9, 2016 from PubMed database.

Sun, Z.& Zhang, N. (2015). Clinical evaluation of CEA, CA19-9, CA72-4 and CA125 in gastric cancer patients with neoadjuvant chemotherapy. World Journal of Surgical Oncology, 12 (1), 397. (Level 4 evidence)

Verberne, C., Zhan, Z., van den Heuvel, E., Grossmann, I., Doornbos, P., Havenga, K., et al. (2015). Intensified follow-up in colorectal cancer patients using frequent carcino-embryonic antigen (CEA) measurements and CEA-triggered imaging: results of the randomized “CEAwatch” trial. EJSO, 41, 1181-1196.  (Level 2 evidence)

ORIGINAL EFFECTIVE DATE:  11/1987

MOST RECENT REVIEW DATE:  10/22/2020

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Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.

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