What Are Cancer Markers (Tumor Markers)?
Cancer markers, also known as tumor markers, are measurable substances—typically proteins—produced either by cancer cells themselves or by the body in response to malignancy, and can be detected in blood, urine, or tissue samples. 1, 2
Definition and Basic Characteristics
Tumor markers are molecules that indicate the presence of cancer and serve as tools for diagnosis, staging, prognosis assessment, and treatment monitoring across various malignancies. 2, 3 These substances have been in clinical use since the discovery of Bence-Jones protein in 1848, with modern markers like AFP (alpha-fetoprotein) and CEA (carcinoembryonic antigen) developed in the 1960s-1970s. 4
Types of Cancer Markers
Cancer markers can be categorized into three main types: 2
- Serum-based markers (most commonly used due to ease and lower cost of testing)
- Radiology-based markers
- Tissue-based markers
Clinical Applications and Limitations
Where Tumor Markers ARE Useful:
Diagnostic aid in high-suspicion cases: PSA for prostate cancer, β-hCG and AFP for germ cell tumors, CA125 for gynecological malignancies, and chromogranin A for neuroendocrine tumors 1, 2
Prognostic assessment: LDH correlates with tumor burden across multiple cancer types; elevated CEA (≥5 mg/mL) indicates poorer prognosis in colorectal cancer; Oncotype DX predicts recurrence risk in ER-positive breast cancer 1
Treatment monitoring: CEA for metastatic colorectal cancer (measured every 1-3 months during active treatment); CA 15-3/CA 27.29 for metastatic breast cancer when combined with imaging and clinical examination 5, 1
Post-treatment surveillance: CEA testing every 3 months for at least 3 years in stage II-III colorectal cancer 1
Where Tumor Markers Are NOT Useful:
Mass screening: Due to poor positive predictive value, insufficient sensitivity, and specificity, most tumor markers cannot screen for early-stage cancer in asymptomatic populations 2, 4, 3
Standalone diagnosis: A positive tumor marker does not confirm malignancy, as markers can be elevated in benign and inflammatory conditions 4, 6
Routine surveillance after curative treatment: The American Society of Clinical Oncology explicitly states that CA 15-3/CA 27.29 should not be used for routine surveillance after primary breast cancer therapy, as early detection of metastatic disease does not improve overall survival or quality of life 5, 7
Important Caveats
Specificity issues: Some markers are cancer-type specific (PSA for prostate), while others are positive across multiple cancer types (CEA, CA19-9). 4 Non-malignant proliferative processes including inflammation and benign conditions can also elevate tumor marker levels. 6
Technical considerations: All measurements for a given patient must be performed in the same laboratory using the same assay technique, as results vary significantly between methods. 7
Interpretation pitfalls: Tumor markers should never be used as the sole criterion for changing therapy—always correlate with clinical and radiographic findings. 7 Spurious early rises may occur during the first 4-6 weeks of new therapy. 5
Emerging Technologies
Multiparameter gene expression assays (such as Oncotype DX) have emerged as valuable tools for predicting recurrence risk and guiding treatment decisions, particularly in breast cancer. 1 The REMARK (Reporting Recommendations for Tumor Marker Prognostic Studies) guidelines have been developed to improve research quality and transparency. 5, 1