by Dr. C.H. Weaver M.D. Updated 02/2022
What is the Carcinoembryonic antigen (CEA)?
CEA is an antigen (small protein) that is found on the surface of colon, rectal, gastric and other types of cancer cells and high levels of CEA can be detected in the blood of some patients with cancer and the developing fetus. The CEA is measured in the blood and the normal range is <2.5 ng/ml in an adult non-smoker and <5.0 ng/ml in a smoker. The most common cancers that elevate CEA are in the colon and rectum but it can be elevated with gastric, ovarian and other cancers. The CEA test most often used for post colon cancer treatment surveillance and is likely to be replaced with ctDNA over time.
What causes CEA blood levels to increase?
The most frequent cancer which causes an increased CEA is cancer of the colon and rectum. Benign conditions which can elevate CEA include smoking, infections, inflammatory bowel disease, pancreatitis, cirrhosis of the liver, and some benign tumors in the same organs in which an elevated CEA level indicates cancer.
What does it mean if you have a high CEA blood level?
CEA is a protein normally found in the tissue of a developing baby in the womb. The blood levels of this protein disappears or becomes very low after birth. In adults, an abnormal level may be a sign of cancer.
Does CEA return to normal after the cancer is removed?
Most healthy people have CEA levels below the 2.5 ng/ml. CEA levels generally return to normal between one and four months after a cancer has been successfully removed.
Can CEA be high without having cancer?
Yes, elevations in CEA and CA 19-9 levels may occur in patients without cancer. In fact studies suggest that falsely elevated levels may occur in up to 50% of colon cancer patients post treatment leading to unnecessary anxiety and testing.
Can CEA levels increase with chemotherapy treatment?
Yes, CEA "flares" during chemotherapy don't mean the cancer is progressing. Cancer patients whose CEA blood tests rise at the beginning of chemotherapy and then fall (CEA flare) do better than patients with a consistently rising CEA.
How do oncologists use the CEA level?
Historically the main role for CEA has been in post colorectal cancer treatment surveillance along with clinical evaluation and CT/PET scans. Rising CEA levels may indicate a cancer recurrence sooner than PET/CT detection however this doesn't necessarily translate into improved survival. Moreover a high CEA level may occur falsely leading to significant anxiety and unnecessary tests to look for a recurrence that doesn't exist.
What Have the studies shown?
Below are some of the key studies that helped define the role of CEA. It is the opinion of the Cancer Connect Editorial team that Tumor Informed ctDNA analyses should replace CEA as the best biomarker for evaluating recurrence risk because it is both more sensitive and more specific than CEA. Learn more here...
The CEA blood test could improve treatment for more than 1 in 6 stage 2 colon cancer patients and many patients who could benefit from the test likely aren’t receiving it.
Using data from the National Cancer Database for 40,844 patients, Mayo Clinic physicians and scientists teamed up to look at benefits of measuring the CEA.1
The researchers found that knowing these blood test results prior to treatment could have changed the classification for 17 percent of stage 2 colon cancer patients from average risk to high risk. High risk stage 2 colon cancer patients are more likely to benefit from chemotherapy treatment following surgery.
The researchers also discovered that, for stage 2 patients who had surgery but not chemotherapy, the five-year survival rate was 66 percent for those with elevated protein levels and 76 percent for those without elevated levels. And for patients with elevated protein levels, those who had chemotherapy and surgery fared better than those who only had surgery.
Levels of CEA Associated with Survival and Recurrences in Early Gastric Cancer
According to results presented in the British Journal of Cancer, levels of the CEA found in a peritoneal wash or blood are indicative of the risk of a cancer recurrence and survival in patients with early gastric cancer.5,6
Although the area of cancer may appear to be completely removed in patients with early gastric cancer, a significantly portion of patients will experience a cancer recurrence and ultimately succumb to this disease. One area in which cancer recurrences are common is the peritoneal cavity; this space in the abdomen is bound by thin membranes and contains the intestines, stomach, and liver. Long-term survival of patients who experiences a cancer recurrence remains poorer than for those who are cured with initial therapy. Researchers have been evaluating ways to predict the risks of cancer recurrences in patients with early gastric cancer. Those with a lower risk of a recurrence may proceed with standard treatment choices, while those with a higher risk may choose more aggressive therapeutic strategies or participate in a clinical trial.
Researchers from Japan evaluated levels of CEA from the peritoneal cavity (using a procedure called a peritoneal wash) in patients with gastric cancer. This trial included 86 patients with early gastric cancer who underwent the complete surgical removal of their cancer. Patients were followed for approximately 30 months. Results showed the following relationships between CEA levels and cancer recurrence:
- Patients with higher CEA levels had a significantly higher rate of cancer recurrences within the peritoneal cavity than those with normal or lower CEA levels.
- Patients with higher CEA levels had a significantly higher mortality rate than those with normal or lower CEA levels.
Researchers have also analyzed blood samples of patients diagnosed with gastric cancer who had been considered cured of the disease after undergoing surgery. A series of blood tests measuring CEA and analyzing its genetic make-up were taken every 2 months. Extensive analysis revealed that clinical recurrence rates were correctly identified a significant portion of the time.
More intensive screening improves overall survival among patients diagnosed with stage II colon cancer
According to an article published in the Journal of Clinical Oncology, more intensive screening up to the fifth year following treatment for patients diagnosed with stage II colon cancer yields improved survival compared with simpler screening strategy.
Researchers from Spain conducted a trial to compare different follow up schedules among patients who had been diagnosed and treated for either stage II or III colon cancer.
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This trial included 259 patients: 132 patients underwent a simple surveillance strategy including a clinical evaluation and carcinoembryonic antigen (CEA) levels, 127 patients underwent an intensive surveillance strategy including abdominal computed tomography (CT) or ultrasound, chest X-rays, and colonoscopy in addition to a clinical evaluation and CEA levels.
Patients with stage II colon cancer had improved outcomes with an intensive surveillance strategy:
- After a median follow-up of 4 years, there was no difference in survival among patients with stage III colon cancer.
- There were no differences in time before cancer recurred and type of recurrence between the two groups screening groups.
- Patients with stage II colon cancer had improved survival when undergoing intensive screening compared to simple screening (81.6 months versus 70.9 months, respectively).
- Patients with cancers in the rectum had improved survival with intensive screening compared to simple screening.
- 51% of patients who underwent intensive screening were able to have their cancer recurrence completely removed, compared with only 29% of patients who underwent simple screening.
- Although intensive screening was more expensive than simple screening, surgery for recurrences was more expensive for those who underwent simple screening.
The researchers concluded that a more intensive screening strategy improves overall survival among patients diagnosed with stage II colon cancer more than a simpler strategy. A consensus on the exact routine of screening for patients with this disease has not yet been confirmed, these results may provide important information on establishing follow-up screening guidelines for stage II colon cancer. Patients diagnosed with stage II colon cancer may wish to speak with their physician regarding their individual follow-up screening recommendations.2
Scans plus Tumor Markers Detect Recurrences Earlier than Either Alone in Colorectal Cancer Patients
According to an article recently published in the British Journal of Cancer, levels of tumor markers plus results from computed tomography (CT) scans predicted cancer recurrences earlier than either method alone among patients with colorectal cancer who had liver metastasis that had been surgically removed.
The liver is a very common site for colorectal cancer to spread-a condition referred to as liver metastasis. The surgical removal of liver metastasis provides the greatest hope for a cure among these patients; however, long-term survival still remains unfavorable as a large majority of these patients will experience a recurrence of their cancer.
Generally, outcomes for cancer recurrences that are detected and treated in their earliest possible stages are better than outcomes for those treated at later stages. Therefore, the most accurate monitoring for recurrences among patients who have had liver metastasis surgically removed may ultimately result in optimal outcomes for these patients.
Tumor makers are molecules that can be detected in circulating blood. These markers are often elevated with the existence and/or recurrence of cancer. Carcinoembryonic antigen (CEA) and the carbohydrate antigen 19-9 (CA 19-9) are two markers whose levels may be tested to determine the presence of colorectal cancer. In addition, CT scans are often used to monitor for recurrences among colorectal cancer patients. Researchers continue to evaluate the most accurate ways to detect colorectal cancer recurrences so that treatment may begin in the earliest stages of recurrence.
Researchers from London conducted a clinical trial to evaluate the effectiveness of CEA plus CA 19-9 and CT scans in monitoring for recurrences among patients with colorectal cancer. This trial included 76 patients who had liver metastasis surgically removed. The patients underwent CEA, CA 19-9 testing, and CT scans every three months following surgery for two years and every six months thereafter.
- Forty-nine percent (37) of patients ultimately developed a cancer recurrence.
- Among the 37 patients who experienced a recurrence, CT scans indicated a recurrence despite normal tumor markers in 19 patients.
- Among the patients who experienced a recurrence, tumor makers indicated a recurrence despite normal CT scans in 12 patients.
- Results from both CT scans and tumor markers significantly improved the accuracy in detecting early recurrences, compared to either method alone.
The researchers concluded that the combination of tumor makers and CT scans appear to improve detection of early recurrences compared to either method alone in colorectal cancer patients who have undergone surgery for liver metastasis.
Patients who have undergone surgery for liver metastasis should discuss the most appropriate follow-up monitoring schedule for the detection of recurrences with their physician.3
CEA and Albumin Levels Associated with Survival in Colorectal Cancer
According to an article recently published in the Journal of Clinical Gastroenterology, levels of the carcinoembryonic antigen (CEA) and albumin (ALB) are associated with survival among patients with early colorectal cancer.
Levels of the protein CEA in the blood may be indicative of the presence or spread of colon cancer. ALB, also a protein that can be measured in the blood, may also indicate some levels of cancerous activity. Researchers are still evaluating CEA and ALB levels and their potential associations with outcomes among cancer patients.
Researchers recently evaluated data to determine the relationship of CEA and ALB levels prior to treatment among patients with early colon cancer. This study included 170 patients who were divided into four groups: 1) low CEA levels and high ALB levels; 2) low CEA and low ALB; 3) high CEA and high ALB; 4) high CEA and low ALB.
- At five years, survival rates were 66% for group 1, 63% for group 2, 46% for group 3, and 34% for group 4.
The researchers concluded that levels of CEA and ALB prior to treatment are significantly associated with long-term survival among patients with early colorectal cancer. These results add to a growing body of evidence that suggests specific cancer and patient characteristics may greatly affect outcomes among patients diagnosed with early colorectal cancer. These findings may ultimately aid in individualizing treatment for these patients.4
- Spindler BA, Bergquist JR, Thiels CA, et al. Incorporation of CEA Improves Risk Stratification in Stage II Colon Cancer. J Gastrointest Surg. 2017 May;21(5):770-777.
- Rodriguez-Moranta F, Salo J, Arcusa A, et al. Postoperative Surveillance in Patients With Colorectal Cancer Who Have Undergone Curative Resection: A Prospective, Multicenter, Randomized, Controlled Trial. Journal of Clinical Oncology. 2006; 24: 386-393.
- Bhattacharjya S, Aggarwal R, Davidson B, et al. Intensive Follow-Up After Liver Resection for Colroectal Liver Metastases: Results of Combined Serial Tumour Marker Estimations and Computed Tomography of the Chest and Abdomen – a Prospective Study. British Journal of Cancer. 2006; 95:21-26.
- Boonpipattanapong T, Chewatanakornkul S, et al. Preoperative Carcinoembryonic Antigen and Albumin in Predicting Survival in Patients With Colon and Rectal Carcinomas. Journal of Clinical Gastroenterology . 2006;40:592-595.
Ito S, Nakanishi H, Kodera Y, et al. Prospective validation of quantitative CEA mRNA detection in peritoneal washes in gastric carcinoma patients. British Journal of Cancer. 2005; 93, 986-992.
Seo J, Choi C, Kim B, et al. Follow-Up Study of Peripheral Blood Carcinoembryonic Antigen mRNA Using Reverse Transcription-Polymerase Chain Reaction as an Early Marker of Clinical Recurrence in Patients with Curatively Resected Gastric Cancer. American Journal of Clinical Oncology. 2005; 28: 24-29.