Carcinoembryonic Antigen (CEA)
CEA is a large family of 36 different, but related, glycoproteins, which are part of the immunoglobulin superfamily. The human CEA gene family is clustered on chromosome 19q and comprises 29 genes. Seven of these 29 genes code for CEA glycoproteins. CEA molecules exhibit considerable heterogeneity due to variation in carbohydrate side chains.
CEA is present in the gastrointestinal tract during fetal life and occurs at low concentrations in adults. CEA was first reported to be quite specific for tumors of the GI tract, but further investigations demonstrated elevations in several other malignant and benign diseases. Elevated CEA levels are suggestive, but not diagnostic of cancer, since elevated levels also occur in a variety of benign conditions.
- Most normal persons have detectable concentrations of circulating CEA. Approximately 85% of adults have CEA levels less than 2.5 ng/mL, while 95% have levels less than 5.0 ng/mL. CEA levels are slightly higher in men than women. The median level is 3.4 ng/mL in men and 2.5 ug/mL in women. Healthy persons seldom have levels above 10 ng/mL
- CEA concentrations are twice as high in smokers; female smokers have a median CEA level of 4.9 ng/mL and male smokers have a median level of 6.2 ng/mL.
- CEA levels are not elevated in maternal serum during pregnancy, since CEA does not cross the placenta.
- The liver is the primary site for metabolism of CEA. Benign diseases that impair liver function reduce CEA clearance, resulting in increased serum levels. CEA levels are elevated in 70% of patients with chronic liver disease and 50% of patients with acute liver disease.
- Elevated levels are also frequently seen in other gastrointestinal diseases including peptic ulcer, pancreatitis, diverticulitis, and inflammatory bowel disease. Benign diseases rarely produce CEA serum levels >10ng/mL.
- CEA levels are slightly elevated in patients with chronic renal failure undergoing dialysis.
Serum CEA is ordered most often for patients with colorectal cancer. Numerous studies have demonstrated that:
- Serum concentrations of CEA tend to be higher in patients with well-differentiated colon cancer compared with poorly differentiated cancer.
- Patients with tumors in the left side of the colon generally have a higher incidence of increased CEA concentrations than those with tumors on the right side.
- Bowel obstruction results in higher CEA concentrations in patients with colorectal cancer. Decompression alone reduces serum CEA levels.
The American Society of Clinical Oncology (ASCO) and the European Group on Tumor Markers recommended that serum CEA should not be used as a screening or diagnostic test for colorectal cancer because it is not sensitive enough. The goal of colorectal cancer screening should be to detect disease at either stage I (Duke’s A) or II (Duke’s B). Using a cutoff of 2.5 ng/mL, CEA is elevated in only 30% of patients with stage I and II cancer. CEA levels cannot distinguish locally invasive premalignant colonic polyps from benign polyps.
Duke’s staging system has been the gold standard for predicting outcome in patients with newly diagnosed colorectal cancer. Additional prognostic factors are particularly needed for patients with stage II (Duke’s B, node-negative) colorectal cancer because 40 to 50% of these patients have aggressive disease and might benefit from adjuvant chemotherapy. The majority of studies suggest that preoperative CEA levels can provide prognostic data in patients with stage II colorectal cancer. High levels are associated with more aggressive disease.
ASCO guidelines recommend that serum CEA levels be obtained preoperatively in patients with colorectal cancer if it will assist in staging and surgical treatment planning. Serum levels of CEA have prognostic utility in patients with newly-diagnosed colorectal cancer. Patients with preoperative serum CEA >5 ng/mL have a worse prognosis, stage for stage, than those with lower levels.
Elevated preoperative CEA levels that do not normalize following surgical resection indicate the presence of residual disease and the need for further evaluation. The circulatory half-life of CEA is approximately 7 days. After successful surgical resection of colorectal cancer, an increased CEA concentration should return to normal within 4 to 6 weeks.
After curative resection of colorectal cancer, 10 to 30% of patients have a recurrence within 5 years. The American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN) guidelines recommend postoperative monitoring of CEA every 3 to 6 months for 5 to 6 years for patients with resected stage II and III colorectal cancers. A Cochrane review performed a metanalysis of 23 studies and determined that a CEA cutoff of 5 ng/mL had a pooled sensitivity of 71% and a pooled specificity of 88% for detecting cancer recurrence.
CEA testing alone is not sufficient for postoperative surveillance because 20 to 30% of patients do not have an elevation of CEA with cancer recurrence. For this reason, ASCO and NCCN recommend a CT scan of the chest, abdomen and pelvis every 6 to 12 months for 3 to 5 years in patients with resected stage II and III colorectal cancer. Colonoscopy is also recommended 1 year after resection.
CEA is the tumor marker of choice for monitoring metastatic colorectal cancer during systemic therapy. CEA should be measured at the start of treatment for metastatic disease and every 1 to 3 months during active treatment. Persistently rising values above baseline should prompt restaging. Caution should be used when interpreting a rising CEA level during the first 4 to 6 weeks of a new therapy, because chemotherapy, such as oxaliplatin, can cause transient increases in CEA concentration due to hepatic toxicity in the absence of disease progression.
Reference range is 0 - 5 ng/mL. A difference of >20% between two CEA measurements is considered medically significant.
Specimen requirement is one red top tube of blood.
Reference
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; 24:5313.
Meyerhardt JA et al. ASCO clinical practice guideline endorsement. J Clin Oncol 2013;31:4465-70.
National Comprehensive Cancer Network. Colon Cancer (version 1.2017). https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf
