SUMMARY: ColoRectal Cancer (CRC) is the third most common cancer diagnosed in both men and women in the United States. The American Cancer Society estimates that approximately 140,250 new cases of ColoRectal Cancer will be diagnosed in the United States in 2018 and over 50,630 patients are expected to die of the disease. CarcinoEmbryonic Antigen (CEA) is a group of highly related glycoproteins involved in cell adhesion and was first described in 1965. CEA is normally produced in gastrointestinal tissue during fetal development and is usually present at very low levels in the serum of healthy adults. Elevated serum levels of CEA are seen in certain malignancies and also in heavy smokers. Measurement of CEA is recommended for patients with colorectal cancer as a surveillance tool for early detection of potentially curable recurrent disease, following primary resection. Further, elevated preoperative CEA in patients with nonmetastatic colorectal cancer is associated with worse outcomes, in patients with early-stage disease (Stages I-III), independent of tumor stage. Lack of CEA normalization after resection of the primary tumor, is indicative of residual occult disease. Clinically, patients with an elevated preoperative CEA and an otherwise normal contrast-enhanced CT of the chest, abdomen, and pelvis proceed to surgery with the assumption that the primary lesion is the source of the elevated CEA.
This study was conducted to determine whether pre or postoperative CEA is more prognostic and more specifically whether patients with elevated preoperative CEA that normalizes after resection of the primary tumor had a risk of recurrence similar to that of patients with normal preoperative CEA. In this retrospective cohort study conducted at a comprehensive cancer center, 1027 consecutive patients with Stage I-III colon cancer who underwent curative resection and who had a preoperative CEA result available, were identified. Patients were then grouped into 3 cohorts – normal preoperative CEA, elevated preoperative but normalized postoperative CEA, and elevated preoperative and postoperative CEA. The Primary end point was Recurrence Free Survival (RFS) at 3 years.
The 3-year RFS rate for the patients with elevated preoperative CEA (N=312) was 82.3% compared with 89.7% for the patients (N=715) with normal preoperative CEA (HR=1.68; P=0.05). This represented a 7.4% higher 3-year RFS among patients with normal preoperative CEA compared with those with elevated preoperative levels. The negative prognostic impact of elevated preoperative CEA was negated in those patients whose CEA normalized in the postoperative period. Patients with elevated postoperative CEA (N=57) had a 3-year RFS of 74.5% compared with 89.4% for the patients with either normal preoperative CEA (N=715) or normalized postoperative CEA (N=142), (HR=2.53; P=0.001). This represented a 14.9% higher 3-year RFS for patients with normal postoperative CEA, regardless of preoperative level, compared to those with elevated postoperative CEA. Multivariate analyses confirmed that elevated postoperative CEA but not normalized postoperative CEA was independently associated with shorter RFS.
It was concluded that elevated preoperative CEA that normalizes after resection is not an indicator of poor prognosis. Patients with elevated postoperative CEA are at increased risk for recurrence especially within the first 12 months after surgery. Routine measurement of postoperative, rather than preoperative CEA is strongly recommended and CEA can be a valuable biomarker and is an early indicator of tumor recurrence. Association of Preoperative and Postoperative Serum Carcinoembryonic Antigen and Colon Cancer Outcome. Konishi T, Shimada Y, Hsu M, et al. JAMA Oncol. 2018;4:309-315
