Appropriate Use and Interpretation of Tumor Markers
Tumor markers should not be used for cancer screening or diagnosis in asymptomatic individuals, but serve critical roles in postoperative surveillance, monitoring treatment response in metastatic disease, and providing prognostic information when used in specific clinical contexts. 1, 2
General Principles
Tumor markers lack the sensitivity and specificity required for screening or establishing a cancer diagnosis. 1, 2 An ideal tumor marker does not exist—these tests are adjuncts that must be interpreted alongside clinical findings, imaging, and histopathology. 3 Establishing a diagnosis based on tumor markers alone is fraught with pitfalls due to nonspecificity. 3
Key Limitations to Remember
- Non-malignant elevations are common: Tumor markers elevate in benign conditions, inflammatory states, and with advancing age. 2, 4
- Spurious early rises occur: Rising levels during the first 4-6 weeks of new therapy may not indicate treatment failure—wait and retest. 1, 2
- Sensitivity varies widely: Only 50-60% of patients with metastatic colorectal cancer have elevated CEA, and similar limitations apply to other markers. 1, 2
Carcinoembryonic Antigen (CEA)
Colorectal Cancer Applications
Do not use CEA for screening—specificity is high but sensitivity is very low for detecting occult colorectal cancers. 1
Preoperative CEA measurement may be ordered to assist in staging and surgical planning, and to establish a baseline for surveillance. 1 Elevated preoperative CEA (≥5 ng/mL) correlates with poorer prognosis but should not determine whether to administer adjuvant therapy. 1
Postoperative surveillance protocol: Measure CEA every 2-3 months for at least 2-3 years in patients with stage II or III disease who are candidates for surgery or systemic therapy. 1, 2 This intensive follow-up combined with CT imaging every 3-12 months demonstrates significant mortality reduction. 1 CEA is the most cost-effective test for detecting potentially resectable metastases—64% of recurrences are detected first by CEA elevation. 1
When CEA is elevated on surveillance: Confirm with retesting, then pursue further evaluation for metastatic disease with imaging. 1 Do not initiate systemic therapy based on CEA elevation alone without radiographic confirmation. 1
Monitoring metastatic disease: Measure CEA at treatment initiation and every 1-3 months during active therapy. 2 Use CEA in conjunction with imaging, history, and physical examination—not alone. 1 In the absence of measurable disease, a rising CEA may indicate treatment failure, but interpret cautiously during the first 4-6 weeks of new therapy. 1, 2
Breast Cancer Applications
Do not use CEA for screening, diagnosis, staging, or routine surveillance after primary breast cancer therapy. 1
For metastatic breast disease: CEA can be used alongside imaging and clinical assessment during active treatment. 1 Only 50-60% of metastatic breast cancer patients have elevated CEA (compared to 75-90% with CA 15-3/CA 27.29). 1 Consider measuring both a MUC-1 assay (CA 15-3 or CA 27.29) and CEA initially—if the MUC-1 assay is elevated, CEA monitoring adds little value. 1
CA 15-3 and CA 27.29 (Breast Cancer)
Do not use for screening, diagnosis, staging, or routine surveillance after primary breast cancer therapy. 1
For monitoring metastatic disease during active therapy: Use CA 27.29 or CA 15-3 in conjunction with imaging, history, and physical examination. 1 Present data are insufficient to recommend these markers alone for monitoring treatment response. 1 In the absence of readily measurable disease, an increasing CA 15-3 or CA 27.29 may indicate treatment failure, but exercise caution when interpreting rises during the first 4-6 weeks of new therapy due to spurious early elevations. 1
CA-125 (Ovarian Cancer)
While the provided evidence focuses primarily on CEA and breast cancer markers, CA-125 is mentioned in the context of screening evaluation. 5, 6 CA-125 combined with ultrasound is under evaluation as a screening modality for ovarian cancer, though its use remains investigational. 5
Important caveat: CA-125 elevates in benign gynecologic conditions including endometriosis and leiomyomas. 4 When evaluating patients with ovarian or uterine disorders, consider measuring multiple markers simultaneously (CA-125, CA 19-9, and chromogranin A) rather than CA-125 alone, as some patients with benign tumors only show elevation in CA 19-9 or chromogranin A. 4
Prostate-Specific Antigen (PSA)
PSA in combination with digital rectal examination is undergoing evaluation as a screening modality for prostate cancer. 5 However, the value of PSA screening in reducing mortality from prostate cancer remains unclear. 6
Critical Interpretation Principles
When to retest: Sample after 5-6 half-lives of the marker in question; if elevated, repeat in 2-4 weeks for additional evidence. 3
When evaluating potential malignancy: Use multiple tumor markers together (such as CEA, CA-125, and CA 19-9) rather than relying on a single marker to improve diagnostic accuracy. 2, 4
Laboratory variability: Measured levels of tumor markers may differ between laboratories and countries—establish baseline values and follow trends within the same laboratory. 1