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.  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.

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 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

ID_BT

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