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UTILITY OF CEA MONITORING IN COLORECTAL CANCER
B K Smruti
Medical Oncologist and Haemato-Oncologist, Bombay Hospital and Post Graduate Institute of Medical Science, Marine Lines, Mumbai.
Carcinoembryonic antigen (CEA) is perhaps the best described and thoroughly studied of the tumour markers. It is a glycoprotein expressed in the glycocalyx of gastro-intestinal mucosal cells especially the colon and rectum. This is estimated usually by radioimmunoassay and levels may vary according to the assay technique used. In serial determinations it is advisable to use the same assay technique throughout. The normal level is 2.5 to 3 ng/ml, but is higher in smokers (upto 5 ng/ml).Elevations of this marker is seen in colonic and rectal malignancies. This is observed when the tumours are well differentiated. Poorly differentiated tumours lose the ability to produce CEA.[1] It is a tumour associated and not a tumour specific antigen with elevations observed in other malignancies such as breast, thyroid, stomach, bladder and lung.[2] Since it is cleared by the liver, biliary obstruction, liver function abnormalities can cause elevations of CEA.[3]
An ideal tumour marker is useful for screening large populations at risk for the cancer, provides prognostic information to guide subsequent therapy, detects recurrence early after a curative resection and helps to make decisions in metastatic disease. The clinical utility of CEA monitoring in colorectal cancer management in the above various scenarios has been debated for decades. Its role is distinctly different in these clinical situations.
Screening : Monitoring CEA to screen the population and detect early resectable and curable colorectal cancers has not fulfilled the expectations. It has a low sensitivity of 40% and is an ineffective screening tool even in the population at high risk of colon cancer. Studies have shown that there would be 250 false positive for every true positive.[3] Thus it is not a valued screening test.
Prognostic factor : Pre-operative CEA levels predict recurrence in patients with stage C (stage III) and in same studies stage B (stage II) as well. In stage B patients the recurrence was 10% if CEA < 2.5 ng/ml and 30% if CEA is above 10 ng/ml. In stage C a pre-operative CEA level greater than 2.5 ng/ml had 1.8 fold greater risk of recurrence4 Moertel et al[5] found it predictive in only stage C. Since there is no prospective data this is still a relatively weak predictive marker. Post-operative CEA levels remaining above 5.0 ng/ml were predictive of recurrence.[6] However occasional patients with elevated pre-operative stable level do not develop a recurrence.
DETECTION OF RECURRENCE AFTER CURATIVE RESECTION
After a curative resection 25% (stage II) and 50-70% (stage III) relapse. This recurrence is incurable unless it is resectable. The five year disease free survival is 23% for patients with resected metastasis.[7] Monitoring CEA post-operatively has been investigated to determine whether this strategy can detect resectable metastasis. Adjuvant chemotherapy may also marginally elevate the levels. A rising CEA is more meaningful than a single elevated level.
A meta-analysis of patients evaluated on follow up after resection showed a 9% improvement in survival for those who underwent CEA monitoring with intensive investigation for elevated CEAcompared to the less intensive follow up. It also showed that patients on intensive follow up were more likely to be resected.[8] A non randomized study showed 54% of metastasis resectable in the group who had CEA monitoring as opposed to 30% for patients with less frequent CEA.[9] A small study revealed a five month lead time for detecting recurrence in the monitored patients. This can translate into survival benefit only if patients can be resected.[10] The final analysis of a UK study about the impact of monitoring on survival is awaited.[11]
CEA MONITORING IN METASTATIC DISEASE
CEA is elevated in 85% of patients with metastatic colorectal cancer[3] and change in CEA levels with treatment also correlates with survival. A decrease with therapy is associated with improved survival[12] and rising CEA correlates with eventual progression of disease. The CEA however does not always correlate with the tumour mass. A necrotic tumour may show a fall in CEA even in the presence of progressive disease. The site of metastasis influences the CEA levels. It is higher in liver metastasis as compared to pulmonary, retroperitoneal or intraperitoneal recurrence.
The availability of 2nd line therapy for metastatic diseases has made it more meaningful to monitor CEA to make therapeutic changes.
CONCLUSION
CEA is an ineffective screening tool even in a high risk population. The pre and post-operative levels have a debatable small predictive value. After a curative resection monitoring CEA detects more resectable recurrence. However, data on its impact on survival is conflicting. One could prudently offer CEA monitoring after curative resection for only those patients who are medically fit to undergo resection of detected metastasis. In the metastatic setting CEA monitoring could serve to guide the clinician to decide on changing 2nd line chemotherapy.
REFERENCES
1.Goslin R, O'Brien MJ, Steele G. Correlation of plasma CEA and CEA tissue staining in poorly differentiated colorectal cancer. Am J Med 1981; 71 : 246-9.
2.American society of clinical oncology. Clinical practice guidelines for the use of tumour markers in breast and colorectal caucer. J Clinic Oncology 1996; 14 : 2843-77.
3.Fletcher RH. Carcinoembryonic antigen. Ann Intern Med 1986; 104 : 66-73.
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6.Steele G, Eilenberg S, Ramming K, et al. CEA monitoring among patients in multi-institutional adjuvant GI therapy protocols. Ann Surg 1982; 196 : 162.
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10.Makela JT, Laitinen SO, Kairaluoma ML. Five year follow up after radical surgery for colorectal cancer results of a prospective randomised trial. Arch Surg 1995; 130 : 1062-7.
11.Northover J. Clinical management of colorectal cancer. International conference of the european association for research in oncology (AERO) Cannes, France, June 20, 1998.
12.Allen Mersh TG, Kemeny N, Niedzwiecki D, et al. Significance of a fall in serum CEA concentration in patients treated with cytotoxic chemotherapy for disseminated colorectal cancer. Gut 1987; 28 : 1625-9.
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