What is the role of carcinoembryonic antigen (CEA) as a tumor marker in rectal cancer?

Role of CEA as a Tumor Marker in Rectal Cancer

CEA is a critical tumor marker in rectal cancer management with established roles in preoperative prognostication, postoperative surveillance, and monitoring metastatic disease, but it should never be used for screening. 1, 2

Screening: Not Recommended

• CEA should not be used as a screening test for rectal cancer due to high specificity but very low sensitivity for detecting occult malignancies 1, 2
• This recommendation is consistent across ASCO and European Group on Tumor Markers guidelines 1

Preoperative CEA Testing: Recommended for Staging and Prognosis

CEA should be measured preoperatively in all rectal cancer patients to assist in staging, surgical planning, and establishing baseline for surveillance. 1, 2

Prognostic Value of Preoperative CEA:

• Elevated preoperative CEA (≥5 ng/mL) is an independent predictor of poor prognosis regardless of other factors 1, 2, 3
• In a multi-institutional Korean study of 1,804 rectal cancer patients receiving neoadjuvant chemoradiotherapy, elevated CEA (>5 ng/mL) was a significant negative predictor of tumor downstaging (downstaging rate: 23.4% vs 42.9% for normal CEA, p<0.001) 3
• Elevated preoperative CEA predicts worse 5-year recurrence-free survival (63.5% vs 74.2%, p<0.001) 3
• Elevated CEA specifically predicts increased risk of distant recurrence rather than locoregional recurrence (p=0.013 vs p=0.732) 4

Important Caveat:

• While elevated preoperative CEA correlates with poorer prognosis, current data are insufficient to use CEA alone to determine whether to administer adjuvant therapy 1
• CEA measurement aids in determining whether the marker will be useful for postoperative surveillance—an elevated preoperative CEA suggests utility for monitoring 1

Postoperative Surveillance: Strongly Recommended

Postoperative CEA should be measured every 3 months for at least 3 years in patients with stage II or III rectal cancer who are potential candidates for surgery or chemotherapy of metastatic disease. 1, 2

Key Surveillance Principles:

• CEA is the most cost-effective test for detecting potentially resectable metastases from colorectal cancer, superior to physical examination, chest x-ray, or other modalities 1
• In the Eastern Cooperative Oncology Group study, CEA was the first test to detect recurrence in 64% of cases with resectable disease 1
• A normal preoperative CEA does not eliminate the need for postoperative surveillance—in patients with recurrent disease and normal preoperative CEA (<5 ng/mL), CEA rises during follow-up in 41-60% of cases depending on timing of measurement 5

Interpretation of Rising CEA:

• Two persistently rising CEA values above baseline warrant further evaluation for metastatic disease, even without corroborating radiographic evidence 1
• An elevated CEA should be confirmed by retesting before initiating extensive workup 1
• ASCO recommends annual CT of chest and abdomen for 3 years, with pelvic CT on the same schedule specifically for rectal cancer surveillance 1

Monitoring Metastatic Disease: Marker of Choice

CEA is the marker of choice for monitoring metastatic rectal cancer during systemic therapy. 1, 2

Monitoring Protocol:

• Measure CEA at the start of treatment for metastatic disease 1
• Repeat every 1-3 months during active treatment 1, 2
• Persistently rising values above baseline suggest progressive disease even without radiographic confirmation 1

Critical Pitfall to Avoid:

• Exercise caution when interpreting rising CEA during the first 4-6 weeks of new therapy—spurious early rises may occur, especially after oxaliplatin use, representing treatment-induced changes rather than progression 1, 6
• Non-cancer conditions can elevate CEA including gastritis, peptic ulcer disease, diverticulitis, liver diseases, COPD, diabetes, and any inflammatory state 1, 2

Special Considerations for Neoadjuvant Chemoradiotherapy

Post-chemoradiotherapy CEA levels have independent prognostic significance in rectal cancer patients receiving neoadjuvant treatment. 7, 8

• Post-chemoradiotherapy CEA <5 ng/mL is associated with increased rates of complete clinical response, pathologic complete response, and improved overall and disease-free survival (p=0.01 and p=0.03) 8
• In patients receiving neoadjuvant chemoradiotherapy, postoperative CEA is an independent prognostic factor for disease-free survival, whereas this relationship is not significant in patients who did not receive neoadjuvant therapy 7
• Post-chemoradiotherapy CEA levels may guide decision-making for alternative treatment strategies in select patients 8

CEA Half-Life Considerations

• Prolonged CEA half-life (≥4.8 days) after resection is an independent predictor of poor prognosis and increased recurrence risk 6
• Patients with CEA half-life ≥4.8 days should be considered high-risk and warrant more intensive surveillance 6

Markers NOT Recommended

Data are insufficient to recommend CA 19-9, DNA ploidy, flow cytometric proliferation analysis, p53, ras, thymidine synthase, microsatellite instability, or other molecular markers for routine management of rectal cancer. 1