Serum Tumor Markers for Gastrointestinal Cancer
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. Serum tumor markers have been investigated in many malignancies, including most myeloma, germ cell (i.e., ovary, testis) tumors, and prostate cancer (e.g., PSA).
Gastrointestinal cancer refers to malignant conditions of the gastrointestinal tract (GI tract) and accessory organs of digestion, including the esophagus, stomach, biliary system, pancreas, small intestine, large intestine, rectum and anus. The National Comprehensive Cancer Network (NCCN) recommends the serum tumor marker carcinoembryonic antigen (CEA) testing as part of the pre-surgical workup and as a surveillance tool for colon and rectal cancers. However, CEA is not recommended as a screening tool for colorectal cancers. NCCN also recommends the use of serum marker CA 19-9 in pancreatic cancers. The NCCN guidelines also note that elevated CA 19-9 does not necessarily indicate cancer or advanced disease, as an elevated CA 19-9 may be the result of biliary infection. They further note that either CEA or CA 19-9 or both can be used in the management of hepatobiliary cancers under certain circumstances.
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.
Serum tumor markers CEA and/or CA 19-9 for the management of gastrointestinal cancer are considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
All other serum tumor markers for the management of all other gastrointestinal cancers are considered investigational.
The use of serum tumor markers is considered medically appropriate if ANY ONE of the following are met:
CA 19-9 is indicated in the management of pancreatic adenocarcinoma for ANY ONE of the following:
As part of the initial workup in symptomatic individuals
Prior to initiation of adjuvant therapy, with or without subsequent resection
To assess for recurrence or metastatic disease
Carcinoembryonic antigen (CEA) testing is indicated for ALL of the following:
In the management of colorectal cancer as indicated by ANY ONE of the following:
Preoperatively to assist in staging and surgical planning
Postoperative follow-up interval of ANY ONE of the following:
First two years post resection, every three to six months
Three to five years post resection, every six months
Follow-up CEA testing not to exceed five years post resection
CEA and/or CA 19-9 for the management of hepatobiliary cancers for ANY ONE of the following:
As part of the initial workup in symptomatic individuals
To determine the need for biopsy to rule out intrahepatic cholangiocarcinoma
As surveillance for disease relapse or progression
Any specific products referenced in this policy are just examples and are intended for illustrative purposes only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available. These examples are contained in the parenthetical e.g. statement.
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits, or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.
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.
American Society of Clinical Oncology. (2006). Update of recommendations for the use of tumor markers ingastrointestinal 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, 2012,3 (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.
eviCore® healthcare. (2019, January) Clinical guidelines: lab management program. Retrieved October 4, 2018 from www.evicore.com.(5 articles and/or guidelines reviewed)
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. (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. (2018, August). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Colon cancer. Version 3.2018. Retrieved October 4, 2018 from www.nccn.org.
National Comprehensive Cancer Network. (2018, August). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Hepatobiliary cancers. Version 3.2018. Retrieved October 4, 2018 from www.nccn.org.
National Comprehensive Cancer Network. (2018, August). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Rectal cancer. Version 3.2018. Retrieved October 4, 2018 from www.nccn.org.
National Comprehensive Cancer Network. (2018, July). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Pancreatic adenocarcinoma. Version 2.2018. Retrieved October 4, 2018 from www.nccn.org.
National Comprehensive Cancer Network. (2018, May). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Gastric cancer. Version 2.2018. Retrieved October 4, 2018 from www.nccn.org.
National Comprehensive Cancer Network. (2018, May). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Esophageal and esophagogastric junction cancers. Version 2.2018. Retrieved October 4, 2018 from www.nccn.org.
National Institute for Health and Care Excellence. (2011). Colorectal cancer: diagnosis and management. Retrieved October 18, 2017 from www.nice.org.uk.
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.and 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: 3/2/2019
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