What is Carcinoembryonic Antigen (CEA) and its sensitivity and specificity for cancer diagnosis?

Carcinoembryonic Antigen (CEA): Sensitivity and Specificity for Cancer Diagnosis

Carcinoembryonic antigen (CEA) is not recommended for cancer screening or diagnosis due to its low sensitivity and insufficient specificity, particularly for early-stage disease. 1, 2

Definition and Biological Function

• CEA is a glycoprotein from a family of 32 genes that functions as an intercellular adhesion molecule 3, 4
• It is normally expressed in various tissues but is produced in excess in essentially all human colon carcinomas and many other carcinoma types 3, 4
• In normal adult intestine, CEA is localized mainly to epithelial cell membranes facing the lumen, while in embryonic intestine and colonic tumors, it is found on adjacent cell membranes 4

Diagnostic Performance for Cancer

• Sensitivity of CEA for detecting cancer is poor, ranging from 17.4% to 100%, but typically between 50% and 80% 5
• Specificity is generally higher, ranging from 66.1% to 98.4%, with most studies showing specificity above 80% 5
• Negative predictive value is generally high (74.5% to 100%), but positive predictive value is less reliable (45.8% to 95.2%) 5
• For colorectal cancer specifically, only 50-60% of patients with metastatic disease will have elevated CEA levels 1
• For advanced epithelial ovarian cancer, CA-125 is elevated in approximately 85% of cases but only about 50% of early-stage cases, making it more sensitive than CEA for this cancer type 6

Clinical Applications

• CEA is not recommended for screening or diagnosis of colorectal cancer due to its low sensitivity and specificity, particularly for early-stage disease 1
• Preoperative CEA may be ordered in patients with colorectal carcinoma for prognostic information and to establish a baseline for postoperative surveillance 1
• Postoperative CEA testing is recommended every 3 months in patients with stage II or III colorectal cancer for at least 3 years if the patient is a candidate for surgery or systemic therapy 1
• For monitoring patients with metastatic colorectal cancer during active therapy, CEA is the marker of choice and should be measured at the start of treatment and every 1-3 months during active treatment 1
• Caution should be used when interpreting rising CEA levels during the first 4-6 weeks of a new therapy, as spurious early rises may occur 1

Limitations and Confounding Factors

• CEA is elevated in multiple non-cancer conditions, including lung fibrosis, uremia, chronic obstructive pulmonary disease, Alzheimer's disease, endometriosis, pelvic inflammatory disease, and cirrhosis 7, 3
• CEA levels increase with age, with individuals older than 65 years having higher baseline levels 3
• When evaluating potential malignancy, additional tumor markers should be considered alongside CEA:
  • CA-125/CEA ratio >25 favors ovarian origin over gastrointestinal origin 7
  • Measuring CEA and CA 19-9 in addition to CA-125 helps distinguish primary ovarian tumors from gastrointestinal metastases 7

Clinical Utility in Specific Cancers

• For colorectal cancer:
  • CEA is not effective at detecting treatable recurrences at an early stage 5
  • A clinically relevant effect on patient mortality from CEA surveillance remains to be proven 5
  • CEA is more sensitive for detecting liver metastases than locoregional or pulmonary metastases 8
• For breast cancer:
  • CEA is not recommended for screening, diagnosis, staging, or routine surveillance after primary therapy 1
  • CEA can be used in conjunction with other methods for monitoring metastatic disease during active therapy 1
• For other cancers:
  • Present data are insufficient to recommend CA 19-9 for screening, diagnosis, staging, surveillance, or monitoring treatment of patients with colorectal cancer 1

In conclusion, while CEA has limited value as a screening or diagnostic tool due to its low sensitivity and specificity, it has established utility in monitoring treatment response and disease recurrence in patients with certain cancers, particularly colorectal cancer.