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Incorporation of CEA Improves Staging in Colon Cancer
Blake Spindler*, John R. Bergquist, Cornelius A. Thiels, Scott Kelley, David W. Larson, Kellie Mathis
Surgery, Mayo Clinic, Rochester, MN

Stage II colon cancer includes stratification into risk groups. High risk features include higher T stage (T4 versus T3), retrieval of <12 lymph nodes, presence of lymphovascular invasion, bowel obstruction or bowel perforation, and poorly differentiated histology. Biologic markers are not currently included in this risk stratification system. We hypothesize that carcinoembryonic antigen (CEA) is an important prognostic marker and can improve discriminatory quality in risk stratification for stage II colon cancer.
The National Cancer Database (NCDB) was reviewed from 2004-2009 for all stage II colon adenocarcinoma patients who underwent curative intent resection. Patients were categorized as high risk or average risk based upon the presence or absence of high risk features. Patients with stage II average risk and an elevated CEA (based on institutional interpretation) were reclassified as high risk in our proposed risk stratification system. Unadjusted Kaplan Meier analysis was performed and the proposed system was compared to the conventional classification. Discriminatory ability was assessed using Concordance Probability Estimates (CPE).
A total of 42,383 patients with stage II colon adenocarcinoma were identified, among which 41,900 (98.9%) had a pre-therapy CEA level reported. Patients in the conventional high-risk group had a 65.0% 60-month overall survival compared to 76.5% in the conventional average risk group (p<0.001). Rates of chemotherapy administration were statistically but not substantially different between normal and elevated CEA groups (24.5% vs. 26.0% p < 0.001). Overall survival at 5 years was significantly improved among patients with normal CEA compared to those with CEA elevation (74.5% vs. 63.4%, p<0.001). Re-stratification of patients by CEA level resulted in movement of 6999 patients (17%) from the average to the high risk group. After re-stratification, high-risk patients had a 66.4% 60-month overall survival compared to 79.7% in the average risk group (p<0.001, Figure). CPE increased for the proposed risk stratification system, confirming increased discriminatory ability (0.634 vs. 0.612 in the proposed system, SE=0.005).
CEA is a readily available and inexpensive test that according to the NCDB is almost universally tested preoperatively. In current clinical practice, it is primarily used as a baseline in the post-operative period to assess for recurrence. The addition of biologic markers, specifically CEA, into risk stratification for stage II colon cancer improves risk stratification and discriminatory quality. This suggests that pre-operative CEA not only has the potential to improve staging of Stage II colon cancer but may also be useful in guiding additional therapy, both of which merit further study.

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