TUMOR MARKERS in Colon Cancer
CEA remains the prototypical solid tumor marker of colon cancer. Despite its lack of specificity, if used correctly, CEA determination is a valuable addition to clinical decision-making in patients who have been diagnosed with colon or rectal carcinoma. CEA is not an appropriate screening test. Whether sampled once or serially, CEA cannot be used to help in the differential diagnosis of an unknown suspected bowel problem or malignancy. When CEA concentrations are determined before primary tumor resection, they may provide additional prognostic value, particularly for patients who have nodal involvement. However, CEA should not be used to stratify patients who are undergoing primary or adjuvant colon cancer therapy.
Serial CEA values obtained postoperatively offer an effective means of monitoring response to therapy. A postoperative CEA titer serves as a measure of the completeness of tumor resection. If a preoperative elevated CEA value does not fall to normal within 2 to 3 weeks after surgery, the resection was most likely incomplete or occult metastases are present. A rising trend in serial CEA values from a normal postoperative baseline (<5 ng/ml) may predate any other clinical or laboratory evidence of recurrent disease by 6 to 9 months.
Serial CEA values parallel either tumor regression or tumor progression during treatment for metastatic disease.Although not quantitatively related to volume of disease, CEA titers most often are highest when either liver or lung metastases are present. The vast majority of patients who respond to treatment will demonstrate a decline in CEA levels. Rising CEA values are almost always incompatible with tumor regression. Despite its accuracy in confirming the presence or absence of disease, the routine use of CEA alone to monitor response to treatment is not recommended, because its impact on survival is not clear.
The controversy regarding patient benefit when second-look surgery is performed solely on the basis of a rise in serial CEA determinations is focused more on the limited options for therapy in patients found to have recurrent disease than on the efficacy of the marker itself. When CEA is monitored correctly, surprisingly few false-positive or false-negative results are found. However, the initial enthusiasm for resection of recurrent disease and claims of durable disease-free survival have evolved to the present realization that probably no more than 10 to 15% of patients whose recurrences are defined, whether by a rise in CEA or by conventional studies, will have disease that is potentially curable with currently available surgical or nonsurgical means. In later applications of radioimmunologic scanning techniques, using either external or intraoperative gamma-scanning, the weak link will still be a lack of effective systemic therapy even when disease recurrence is found early.
When liver or lung is the first or only site of recurrence, the serial CEA rise will show the steepest slope. Specific diagnostic tests to confirm recurrence in the liver or lung are now preferable to so-called blind CEA-directed second-look procedures. At present, only patients who have recurrence of colon cancer that necessitates palliation or patients with defined isolated liver or lung metastases should undergo surgery. Therefore, it is recommended that postoperative monitoring of CEA be reserved for patients who would be potential candidates for resection of liver or lung metastases if they occur. As with other follow-up testing, the optimal frequency of serial CEA determinations has not been established.