The use of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) tumor markers in screening for gastrointestinal cancer is still reaping the pros and cons. These tests have been used as a screening tool because they are easy, and the results are fast.

Carcinoembryonic Antigen And Carbohydrate Antigen 19-9 For Screening Gastrointestinal Cancer

The gastrointestinal tract is the most common location of cancer. Colorectal cancer, pancreatic carcinoma, and gastric cancer are some types of gastrointestinal cancer with high mortality rates. Screening is essential, especially for people at risk, both symptomatic and asymptomatic, to increase life expectancy.

According to the Current American Cancer Society Guidelines and Screening Issue, people who are at high risk of developing gastrointestinal cancer, especially colorectal cancer, are those who have the following history:
a. adenoma polyps,
b. curative-intent resection,
c. family history of gastrointestinal cancer,
d. inflammatory bowel disease,
e. and those suspected of having Familial Adenomatous Polyposis (FAP) from Hereditary Non-Polyposis Colorectal Cancer

Unfortunately, The early diagnosis is difficult because the symptoms of gastrointestinal cancer are not specific. When symptoms appear, gastrointestinal cancer is generally already at a high stage. Fiberoptic endoscopy and radiological examinations are invasive and risk causing complications such as bleeding, perforation, and aspiration, making it less suitable for use as a screening tool. Therefore, more effective and simple screening tools are needed to find cancer at an early stage.

In recent decades, serological examinations of tumor markers have begun to be widely used in solid tumor management, both to monitor recurrence and as a screening tool. An ideal examination of tumor markers should be cheap and easy to do, can be used as a screening and diagnostic tool, and can provide prognostic information.

Overview of CEA and CA 19-9

Carcinoembryonic antigen (CEA) was initially discovered by Gold and Freedman in 1965 when they identified fetal colon and colorectal cancer. This antigen is not found in the healthy adult colon, and even if there is, the levels are very low. CEA is a glycoprotein that is on the cell surface and can enter the blood circulation.

Carbohydrate Antigen 19-9 (CA 19-9) is a substance produced by the pancreatic exocrine glands' cancer cells and can be detected on blood tests. The CA 19-9 tumor marker is found as a monoclonal antibody from mice injected with colorectal cancer cells. Epitope CA 19-9 is also normally present in the biliary tract. Thus, if there is a disease in the biliary tract, CA 19-9 levels can also increase.

CEA and CA 19-9 Clinical Use and Normal Values

Carcinoembryonic Antigen (CEA) is a marker for various types of cancer, especially gastrointestinal cancer. In clinical settings, these tumor markers are often combined with other examinations to monitor cancer treatment, including response to treatment and recurrence, indicators of the number or size of cancer, determine prognosis, and estimate cancer stage.

The normal CEA value in plasma is around 2.5-3.5 ng / ml. Smoking can affect CEA results, so the benchmark CEA standard value in smokers is different, which is 5-6.5 ng/ml. High pre-operative CEA levels are a poor prognostic indicator. Other diseases that can increase CEA levels include inflammatory bowel disease, acute alcoholic pancreatitis, alcoholic cirrhosis, and chronic bronchitis.

The purpose of the CA 19-9 examination are:
- diagnose pancreatic cancer, 
- distinguish pancreatic cancer from bile duct cancer or other non-cancerous conditions (such as pancreatitis), 
- monitor the response to therapy, 
- and monitor the prognosis of pancreatic cancer.

Normal CA 19-9 levels in serum are less than 37 U / ml. The evaluation of serum CA 19-9 levels are used to support radiological results to determine whether the tumor can be resected. High CA 19-9 levels are usually found at tumor sizes ≥3 cm and are the limits of tumor resection.

Disadvantages of CEA and CA 19-9 as a Screening Tool

CEA and CA 19-9 examination have the advantage that it is cheaper in terms of cost, easy to do, and the inspection results quickly obtained. Examination of CEA and CA 19-9 in cancer patients who have undergone therapy can also be used as an indicator of cancer recurrence, assess progression, and assess the efficacy of a given regimen.

On the other hand, CEA is not specific for gastrointestinal cancer. CEA can also be detected in large numbers in patients with lung cancer, breast cancer, and ovarian cancer. CEA concentration in serum also depends on various factors, such as inflammation and whether the patient smokes. Increased levels of CA 19-9 can also be found in patients with pancreatitis and ovarian cancer.

Specificity and Sensitivity of CEA and CA19-9 Tumor Markers in Gastrointestinal Cancer Screening

The American Society of Clinical Oncology (ASCO) states that CEA and CA 19-9 should not be used as a screening tool for gastrointestinal cancer. Some literature also shows that CEA and CA 19-9 are not useful for screening asymptomatic populations. Apart from being not specific to gastrointestinal cancer alone, the difference between malignancy and benign disease cannot be made solely based on CEA or CA 19-9 levels. However, any increase in the level of these tumor markers should raise suspicion and require follow-up.

In Korea, A study involved 70,940 asymptomatic subjects. Of these subjects, increased CA 19-9 were found in 1063 people (1.5%), but only four were eventually diagnosed with pancreatic cancer. The results of this study show that although the sensitivity and specificity of CA 19-9 are quite high (100% and 98.5%), the positive predictive value is only 0.9% in the asymptomatic population.

Meanwhile, another study conducted cancer detection by CEA and CA 19-9 examination in 202 subjects with gastrointestinal symptoms. In this study, the specificity of CEA and CA 19-9 was the same, namely 94%. Meanwhile, the sensitivity of CEA is 53%, and CA 19-9 is only 29%.

Kotzev et al. conducted a review of various existing literature related to this topic. They concluded that CA 19-9 and CEA were not suitable for screening or detecting early gastrointestinal cancer. Nevertheless, these two tumor markers still have a place as a prognostic and monitoring tool in managing gastrointestinal cancer.

Source Pict:

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