Carcinoembryonic antigen (CEA) is a glycoprotein, which is present in normal mucosal cells but increased amounts are associated with adenocarcinoma, especially colorectal cancer. CEA therefore has a role as a tumour marker. Sensitivity and specificity are low, however, so it is of more use for monitoring than for screening or diagnosis.
CEA levels are useful in assessing prognosis (with other factors), detecting recurrence (especially for disease that cannot be evaluated by other means) and monitoring treatment in people with colorectal cancer. CEA is particularly recommended for postoperative follow-up of patients with stage II and III colorectal cancer if further surgery or chemotherapy is an option.
CEA may be elevated in colorectal cancer, which is where it is most clinically useful. However, it may also be elevated in a wide variety of other malignant and benign conditions.
Malignant conditions which may have elevated CEA include:
- Colorectal cancer.
- Breast cancer.
- Lung cancer.
- Cancer of the stomach.
- Cancer of the oesophagus.
- Cancer of the pancreas.
- Medullary thyroid carcinoma.
- Skeletal metastases. (May occasionally be a useful screening tool for distinguishing skeletal metastases of tumours above from primary bone or haematological malignancy.)
Non-malignant conditions which may have elevated CEA include:
- Non-malignant liver disease, including cirrhosis, chronic active hepatitis, viral hepatitis and obstructive jaundice.
- Chronic kidney disease.
- Inflammatory bowel disease.
- Irritable bowel syndrome.
- Respiratory diseases - eg, pleural inflammation, pneumonia.
Individual laboratory normal ranges vary but CEA level is usually deemed to be normal at 2.5-5 μg/L. Increasing levels of CEA suggestive of active disease may be more clinically helpful than absolute level. Levels exceeding 10 μg/L are rarely due to benign disease or the moderate elevation that may occur due to smoking.
Sensitivity in early-stage colorectal cancer is very low and increases with the stage of the disease. Studies reporting sensitivity vary in the cut off for what constitutes a normal CEA level so results are varied. Using a cut-off point of 5 μg/L, the proportions of patients with increased values are 3%, 25%, 45% and 65% for patients with Dukes' A, B, C and D disease respectively. Around 72% of cases with unresectable or metastatic disease have elevated CEA levels.
Indications for CEA measurement
Due to the low sensitivity and specificity of the CEA test, it is not recommended that it be used for screening of healthy individuals or for the diagnosis of early colorectal cancer. A CEA level should be ordered only after malignancy has been confirmed.
- The CEA test is of much more use in determining prognosis than it is as an early diagnostic test for colon cancer.
- CEA levels are more likely to be elevated in advanced disease.
- Monitoring treatment:
- The major role for CEA levels is in following patients for relapse after intended curative treatment of colorectal cancer.
- CEA levels typically return to normal within four to six weeks after successful surgical resection. The CEA level can also be used to assess the response to chemotherapy.
- It is recommended that people with stage II or III colorectal cancer have CEA surveillance every three months for at least three years after treatment. National Institute for Health and Care Excellence (NICE) guidelines recommend at least every six months, although most other authorities recommend every three months.[4, 7]
- Clinical trials have shown improvement in survival after five years in patients who underwent CEA monitoring as part of post-treatment management.[4, 8]However, normal levels do not necessarily indicate that recurrence has not occurred.
Similar considerations apply to the diagnosis of breast cancer. The sensitivity of CEA is too low for it to be used as a primary diagnostic test.
In conjunction with other tumour markers (CA27.29, tissue polypeptide antigen and especially CA 15-3), it may however be helpful in the following:
- Disease surveillance.
- Identifying patients with skeletal metastases.
- Predicting response to chemotherapy.
It is not recommended in the routine surveillance of breast cancer and should not be used in isolation for monitoring in advanced disease.One study suggested that it may be helpful in determining prognosis.
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- Primrose JN, Perera R, Gray A, et al; Effect of 3 to 5 years of scheduled CEA and CT follow-up to detect recurrence of colorectal cancer: the FACS randomized clinical trial. JAMA. 2014 Jan 15 311(3):263-70. doi: 10.1001/jama.2013.285718.
- Sturgeon CM, Lai LC, Duffy MJ; Serum tumour markers: how to order and interpret them. BMJ. 2009 Sep 22 339:b3527. doi: 10.1136/bmj.b3527.
- Tumour marker requesting. Guidance for non-specialists; Pathology Harmony, June 2012
- Tsukushi S, Katagiri H, Kataoka T, et al; Serum tumor markers in skeletal metastasis. Jpn J Clin Oncol. 2006 Jul 36(7):439-44. Epub 2006 Jun 30.
- Sturgeon CM, Duffy MJ, Stenman UH, et al; National Academy of Clinical Biochemistry laboratory medicine practice guidelines for use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers. Clin Chem. 2008 Dec 54(12):e11-79. doi: 10.1373/clinchem.2008.105601.
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- Colorectal cancer: The diagnosis and management of colorectal cancer; NICE Clinical Guideline (November 2011)
- Jeffery M, Hickey BE, Hider PN; Follow-up strategies for patients treated for non-metastatic colorectal cancer. Cochrane Database Syst Rev. 2007 Jan 24 (1):CD002200.
- Hara M, Kanemitsu Y, Hirai T, et al; Negative serum carcinoembryonic antigen has insufficient accuracy for excluding recurrence from patients with Dukes C colorectal cancer: analysis with likelihood ratio and posttest probability in a follow-up study. Dis Colon Rectum. 2008 Nov 51(11):1675-80.
- Brooks M; Breast cancer screening and biomarkers. Methods Mol Biol. 2009 472:307-21.
- Duffy MJ; Serum tumor markers in breast cancer: are they of clinical value? Clin Chem. 2006 Mar 52(3):345-51. Epub 2006 Jan 12.
- Yonemori K, Katsumata N, Noda A, et al; Development and verification of a prediction model using serum tumor markers to predict the response to chemotherapy of patients with metastatic or recurrent breast cancer. J Cancer Res Clin Oncol. 2008 Nov 134(11):1199-206. Epub 2008 Jun 5.
- Uehara M, Kinoshita T, Hojo T, et al; Long-term prognostic study of carcinoembryonic antigen (CEA) and carbohydrate antigen 15-3 (CA 15-3) in breast cancer. Int J Clin Oncol. 2008 Oct 13(5):447-51. Epub 2008 Oct 23.
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