The Three Primary Tumor Markers
The three most widely used and clinically validated tumor markers are carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), and human chorionic gonadotropin (HCG). 1
Clinical Utility of the Three Primary Markers
1. Carcinoembryonic Antigen (CEA)
CEA is the marker of choice for monitoring metastatic colorectal cancer during systemic therapy and for postoperative surveillance. 2
For colorectal cancer surveillance, CEA should be measured every 3-6 months for at least 3 years after diagnosis in patients who are candidates for surgery or systemic therapy. 2
An elevated CEA level, if confirmed by retesting, warrants further evaluation for metastatic disease but does not by itself justify systemic therapy. 2
CEA should be measured at the start of treatment for metastatic disease and every 1-3 months during active treatment, with persistently rising values suggesting progressive disease. 2
CEA also contributes to treatment decisions in metastatic breast cancer, though it is not recommended for screening, diagnosis, staging, or routine surveillance after primary breast cancer therapy. 2
2. Alpha-Fetoprotein (AFP)
AFP is essential for the management of nonseminomatous germ cell testicular tumors, where it aids in diagnosis, staging, and monitoring for recurrence. 1
AFP should be measured in males with suspected germ cell tumors as part of the diagnostic workup. 2
AFP levels are more likely to be elevated with advancing stage of disease, and rising levels after therapy almost always indicate recurrent disease. 1
AFP cannot be used for cancer screening but provides critical prognostic information when elevated. 1
3. Human Chorionic Gonadotropin (HCG)
HCG is the only tumor marker that approaches the ideal, particularly in gestational trophoblastic tumors, where it suggests diagnosis and stage, confirms response to therapy, and predicts relapse. 1
Beta-HCG should be measured in males with suspected germ cell tumors alongside AFP. 2
In nonseminomatous germ cell testicular tumors, HCG levels correlate with disease stage and rising levels post-therapy indicate recurrence. 1
HCG is the most reliable tumor marker available, with the level in blood being representative of tumor mass and detectable in occult disease. 1
Important Clinical Caveats
These three markers (CEA, AFP, HCG) are the most intensely studied and widely used tumor markers in clinical practice. 1
None of these markers should be used for mass screening due to poor positive predictive value in the general population. 3
CEA may be falsely elevated during chemotherapy, so waiting until chemotherapy is finished to initiate surveillance is advised. 2
Caution is needed when interpreting rising CEA during the first 4-6 weeks of new therapy, as spurious early rises may occur, especially after oxaliplatin. 2
While other markers exist (CA 19-9, CA 125, CA 15-3, PSA), the three primary markers (CEA, AFP, HCG) have the strongest evidence base and broadest clinical utility across multiple cancer types. 1, 3