Is there a role for Alpha-Fetoprotein (AFP) and Carcinoembryonic Antigen (CEA) in cancer management?

Role of AFP and CEA in Cancer Management

AFP and CEA have highly specific, limited roles in cancer management—neither should be used for screening or diagnosis, but both serve as valuable tools for prognosis, surveillance, and monitoring treatment response in select malignancies.

Alpha-Fetoprotein (AFP)

Hepatocellular Carcinoma (HCC)

AFP is the primary serum marker for HCC management, with elevated levels (>200-400 ng/mL) indicating poor prognosis across multiple treatment modalities. 1

• Prognostic stratification: Elevated AFP predicts increased risk of tumor recurrence after resection, higher drop-out rates from transplant waiting lists, worse survival after liver transplantation, and poorer response to loco-regional therapies 1

• Surveillance in advanced disease: AFP levels >200 ng/mL or >400 ng/mL should be tested as prognostic factors in research investigations and clinical decision-making for advanced HCC 1

• Critical limitation: AFP does not meet rigorous biomarker criteria established by EASL guidelines—it has not demonstrated independent prognostic value in properly powered randomized studies with external validation 1

Other Malignancies

• Gastric adenocarcinoma: In the subset of gastric cancers with elevated AFP (rare presentation), AFP changes correlate better with radiologic treatment response (94.1% concordance) compared to CEA (70.6% concordance), making it superior for monitoring therapy 2

• Germ cell tumors: AFP serves as a diagnostic and monitoring marker alongside beta-hCG and LDH 3

Carcinoembryonic Antigen (CEA)

Colorectal Cancer (Primary Application)

CEA is the marker of choice for monitoring metastatic colorectal cancer during systemic therapy, but should never be used alone without imaging confirmation. 4, 5

Surveillance Protocol for Stage II-III Disease:

• Measure CEA every 3 months for at least 3 years post-diagnosis in patients who are candidates for surgery or systemic therapy 4, 5
• Combine with annual CT chest/abdomen for 3 years (add pelvic CT for rectal cancer) 4
• Preoperative CEA ≥5 ng/mL indicates worse prognosis regardless of tumor stage 4

Monitoring Metastatic Disease:

• Measure CEA at treatment initiation, then every 1-3 months during active therapy 4, 5
• Use in conjunction with imaging, history, and physical examination—never as sole indicator 1
• Beware spurious rises: CEA may transiently elevate during the first 4-6 weeks of new chemotherapy; interpret cautiously during this window 1, 4, 5
• Persistently rising CEA above baseline strongly suggests progression even without radiographic confirmation 4

When CEA Alone May Guide Decisions:

• In the absence of readily measurable disease, an increasing CEA may indicate treatment failure and prompt imaging or therapy change 1

Breast Cancer (Secondary Application)

CEA has minimal utility in breast cancer—it is elevated in only 50-60% of metastatic cases compared to 75-90% for CA 15-3/CA 27.29. 1, 5

• Not recommended for: Screening, diagnosis, staging, or routine surveillance after primary therapy 1

• Limited monitoring role: For metastatic disease during active therapy, CEA can supplement imaging and clinical assessment 1

• Practical approach: Initially measure both a MUC-1 assay (CA 15-3 or CA 27.29) and CEA; if MUC-1 is elevated, CEA adds no value; if MUC-1 is normal, CEA may provide supplementary information in selected cases 1

Gynecologic Malignancies

CEA's primary gynecologic role is distinguishing ovarian from gastrointestinal primaries when imaging shows peritoneal carcinomatosis of uncertain origin. 6

• Measure CEA alongside CA-125 to calculate ratios that help differentiate ovarian versus GI malignancy 6
• Do not use for screening, diagnosis, or routine surveillance of gynecologic cancers 6

Critical Pitfalls and Limitations

Poor Screening Performance (Both Markers)

• Neither AFP nor CEA should be used for population screening due to low sensitivity and specificity for early-stage disease 5
• CEA is elevated in only 50-60% of metastatic disease cases 1, 5

Benign Causes of Elevation

• CEA: Elevated by gastritis, peptic ulcer disease, inflammatory bowel disease, benign biliary obstruction, cholangitis, liver abscess, and increases with age 4, 6, 5
• AFP: Elevated in cirrhosis and other benign hepatic conditions 1

Interpretation Errors to Avoid

• Never initiate systemic therapy based on elevated markers alone without radiographic or pathologic confirmation of metastatic disease 4
• Always confirm elevated results with retesting before extensive workup 4
• Consider non-malignant causes before assuming cancer recurrence or progression 4, 5

Algorithmic Approach to Marker Use

For suspected HCC:

1. Measure AFP at diagnosis for prognostic stratification
2. Use AFP >200-400 ng/mL as poor prognostic indicator across all treatment modalities
3. Monitor AFP serially in advanced disease, but combine with imaging

For colorectal cancer:

1. Obtain preoperative CEA for prognosis (≥5 ng/mL = worse outcome)
2. Stage II-III: CEA every 3 months × 3 years + annual CT × 3 years
3. Metastatic disease: CEA every 1-3 months with imaging; rising CEA prompts imaging if no measurable disease
4. Ignore CEA changes in first 4-6 weeks of new therapy

For breast cancer:

1. Do not routinely use CEA
2. If monitoring metastatic disease, prioritize CA 15-3/CA 27.29 over CEA
3. Only add CEA if MUC-1 assays are normal

For unknown primary with peritoneal disease:

1. Measure both CEA and CA-125 to help differentiate GI versus ovarian origin