What is a CEA (Carcinoembryonic Antigen) test?

What is CEA (Carcinoembryonic Antigen)?

CEA is a glycoprotein tumor marker primarily used for monitoring cancer treatment response and detecting recurrence in patients with known malignancies—particularly colorectal cancer—but it should never be used for cancer screening or diagnosis in asymptomatic individuals. 1, 2

Basic Definition and Structure

CEA is a glycoprotein with a molecular weight of approximately 200,000 daltons that was first identified in colonic cancer tissue in 1965. 3, 4 It belongs to a family of 32 genes and is normally expressed in various tissues throughout the body. 5

What CEA Testing Measures

• The test measures CEA levels in blood serum through radioimmunoassay, with a normal threshold typically set at 5 ng/mL or less. 1, 6
• Levels above 5 ng/mL warrant clinical attention, though values between 2.5-5 ng/mL may be seen in smokers and patients with inflammatory conditions. 4
• Markedly elevated levels (>25 ng/mL) are highly suggestive of metastatic cancer, particularly liver metastases. 4

Primary Clinical Applications

Prognostic Information

• Preoperative CEA levels ≥5 ng/mL indicate worse prognosis in colorectal cancer patients regardless of tumor stage. 1, 6
• Elevated preoperative CEA correlates with shorter disease-free intervals and lower survival rates across colorectal, breast, and lung cancers. 3

Monitoring Treatment Response

• CEA is the marker of choice for monitoring metastatic colorectal cancer during systemic therapy, measured at treatment initiation and every 1-3 months during active treatment. 1, 2
• Two consecutive rising values above baseline strongly suggest disease progression even without radiographic confirmation. 1, 6
• Critical caveat: CEA may be transiently elevated during the first 4-6 weeks of new chemotherapy (especially oxaliplatin), so interpret cautiously during this period. 1, 2

Detecting Cancer Recurrence

• For stage II or III colorectal cancer patients, measure CEA every 3 months for at least 3 years postoperatively. 1, 6
• CEA detects 58-64% of all recurrences before other modalities, making it the most cost-effective test for identifying potentially resectable metastases. 6
• In colorectal cancer, serial CEA increase is the first sign of recurrence in 70-85% of cases; in breast cancer, 40-50% of cases. 3

What CEA Cannot Do

Not for Screening or Diagnosis

• The American Society of Clinical Oncology explicitly recommends against using CEA for cancer screening in asymptomatic populations due to insufficient sensitivity and specificity. 1, 2, 6
• Only 50-60% of patients with metastatic colorectal cancer have elevated CEA levels, demonstrating its limited sensitivity for early-stage disease. 2
• CEA should never be used to diagnose cancer or determine whether to administer adjuvant therapy. 1

Cancers Associated with CEA Elevation

• Colorectal cancer: Most common association and primary clinical use. 1, 3
• Breast cancer: Elevated in 50-60% of metastatic cases; can be used for monitoring metastatic disease during active therapy. 1, 2
• Lung cancer: Particularly adenocarcinoma, though not organ-specific. 7, 5
• Pancreatic cancer: Approximately 30% show elevation; one of the few localized tumors producing significant CEA elevation. 1, 8
• Cholangiocarcinoma: Elevated in approximately 30% of patients. 1

Non-Cancer Causes of Elevated CEA

Important pitfall: CEA is not cancer-specific and can be elevated in numerous benign conditions. 1, 2

• Gastrointestinal conditions: Gastritis, peptic ulcer disease, inflammatory bowel disease (Crohn's disease, ulcerative colitis). 1
• Liver diseases: Benign biliary obstruction (especially with coexistent cholangitis or liver abscess), cirrhosis. 1
• Pulmonary conditions: Chronic obstructive pulmonary disease, lung fibrosis. 5
• Renal disease: Uremia. 5
• Smoking: Active smokers commonly have mildly elevated CEA levels. 4
• Aging: CEA levels naturally increase with age in healthy individuals over 65 years. 5

Clinical Algorithm for Elevated CEA

Step 1: Confirm the Result

• Always retest to verify any elevated CEA before proceeding with extensive workup. 1, 6

Step 2: Consider Non-Malignant Causes

• Evaluate for inflammatory conditions, liver disease, smoking history, and metabolic disorders before assuming malignancy. 1

Step 3: If Confirmed and Concerning

• Perform CT scans of chest, abdomen, and pelvis to identify potential metastatic sites. 1
• For colorectal cancer patients, focus on common metastatic sites including lungs and peritoneum. 1

Step 4: Do NOT Start Treatment Based on CEA Alone

• An elevated CEA alone does not justify initiation of systemic therapy without radiographic or pathologic confirmation of metastatic disease. 1, 6

Survival Impact of CEA Monitoring

• Intensive follow-up incorporating CEA testing every 3-6 months is associated with significant mortality reduction (p=0.007). 6
• Early detection through CEA monitoring enables higher resection rates for asymptomatic disease (17.8%) compared to symptomatic detection (3.1%). 6
• Meta-analyses demonstrate that surveillance protocols using CEA and liver imaging show significant overall survival benefit (RR 0.71; 95% CI 0.60-0.85; p=0.0002). 6