Colorectal cancer is a common malignancy, and managing the disease requires tools to track its status. Biological indicators, known as tumor markers, assist physicians in understanding how a patient’s cancer is progressing and responding to therapy. These markers are substances, often proteins, found in higher than normal concentrations in the blood or tissues of individuals with cancer. While a single tumor marker test cannot diagnose colon cancer, the results offer important data that, combined with imaging and clinical exams, help guide the patient’s care journey.
What Are Tumor Markers and How Are They Used
Tumor markers are molecules produced either directly by cancer cells or by the body in response to the presence of cancer or certain non-cancerous conditions. These substances can include proteins, hormones, or other molecules found in blood, urine, or tumor tissue. In the context of colon cancer, these markers have three main clinical applications, none of which involve initial screening for the general population.
The primary use is monitoring treatment effectiveness, such as chemotherapy or radiation, by checking if marker levels decrease. Physicians also use these tests to detect potential cancer recurrence after successful initial treatment, often before symptoms appear or are visible on scans. Furthermore, certain markers can help determine the likely prognosis, offering an indication of how aggressive the disease may be.
Carcinoembryonic Antigen (CEA): The Standard Monitoring Marker
The Carcinoembryonic Antigen, or CEA, is the most widely recognized and routinely used tumor marker for colorectal cancer. CEA is a glycoprotein that is measured through a simple blood test. It is primarily utilized for monitoring the disease in patients who have already completed treatment, such as surgery or chemotherapy.
The main role of CEA testing is surveillance for disease recurrence. After a tumor is successfully removed, the CEA level is expected to drop, establishing a new baseline measurement. A subsequent, sustained rise in CEA levels over multiple tests can suggest that the cancer may have returned, sometimes giving a lead time of several months before a recurrence is confirmed by imaging.
Monitoring CEA is also valuable for tracking the response to ongoing treatment for advanced disease. If chemotherapy is effective, the CEA level should decrease; if the level continues to rise, it may indicate that the current treatment is not controlling the tumor growth.
However, an elevated CEA level is not specific to cancer. Non-cancerous conditions like inflammatory bowel disease, liver conditions, and smoking can also cause levels to increase. Generally, healthy non-smokers have a CEA level below 3.0 nanograms per milliliter (ng/mL), but the exact cutoff for concern is determined by the patient’s specific history and baseline measurements.
Molecular Markers Guiding Treatment Decisions
Distinct from protein markers like CEA, molecular markers are genetic alterations analyzed directly from the tumor tissue, playing a crucial role in modern, personalized treatment planning. These markers are predictive, meaning they help determine which specific therapies will be most effective for an individual patient. The analysis of these genetic changes ensures that the therapy is targeted to the specific biology of the tumor.
One important group of molecular markers involves the RAS genes (KRAS and NRAS). When mutated, these genes can lead to uncontrolled cell growth and are found in 40 to 50 percent of colorectal cancers. A RAS mutation typically predicts that the tumor will not respond to anti-epidermal growth factor receptor (EGFR) therapies. Testing for RAS mutations is standard practice to identify patients who would benefit from these targeted treatments.
Another significant marker is the BRAF gene mutation, which is present in approximately 8 to 10 percent of advanced colorectal cancers and is generally associated with a poorer prognosis. Similar to RAS mutations, the BRAF mutation status also influences treatment selection, often requiring a combination of targeted drugs to overcome the resistance mechanisms it causes.
Testing for Microsatellite Instability (MSI) status assesses the tumor’s DNA repair capabilities. Tumors classified as MSI-High (MSI-H) have high genetic instability due to a deficient mismatch repair (dMMR) system and often respond well to immunotherapy. This testing identifies patients who can benefit from immune checkpoint inhibitors, a type of drug that harnesses the body’s own immune system to fight the cancer.
Interpreting Results and Understanding Limitations
Tumor marker results are only one piece of the clinical picture and must be interpreted alongside other information, such as radiology scans and a patient’s physical symptoms. A single elevated reading is rarely sufficient to change a treatment plan or confirm recurrence. Instead, physicians focus on the trend of the marker level over a period of time, looking for a consistent and significant increase or decrease.
The tests are not perfect and are subject to limitations, including false positives and false negatives. A false positive occurs when the marker level is high due to a non-cancerous condition, like inflammation, but is mistakenly attributed to cancer recurrence. Conversely, a false negative happens when cancer is present, but the tumor cells do not produce detectable levels of the marker, or the cancer is in an early stage.
Up to 30 percent of people with colon cancer may not have an elevated CEA level at all. Therefore, tumor markers function as surveillance tools and predictive guides, requiring a physician’s expertise to place the results in the full context of a patient’s health history.