Early Postoperative Serum Carcinoembryonic Antigen Is a Stronger Independent Prognostic Factor for Stage II Colorectal Cancer Patients Than T4 Stage and Preoperative CEA

Abstract

Background: Serum carcinoembryonic antigen (CEA) is an important biomarker for diagnosis, prognosis, recurrence, metastasis monitoring, and the evaluation of the effect of chemotherapy in colorectal cancer (CRC). However, few studies have focused on the role of early postoperative CEA in the prognosis of stage II CRC.

Methods: Patients with stage II CRC diagnosed between January 2007 and December 2015 were included. Receiver operating characteristic (ROC) curves were used to obtain the cutoff value of early postoperative CEA, CEA ratio and CEA absolute value. The areas under curves (AUCs) were used to estimate the predictive abilities of the CEA and T stage. The stepwise regression method was used to screen the factors included in the Cox regression analysis. Before and after propensity score (PS) - adjusted Cox regression and sensitivity analysis were used to identify the relationship between early postoperative CEA and prognosis. Meta-analysis was performed to verify the results. Kaplan-Meier survival curves were used to estimate the effects of CEA on prognosis.

Results: We included 1081 eligible patients. ROC curves suggested that the cutoff value of early postoperative CEA was 3.66 ng/ml (P <0.001) and the AUC showed early postoperative CEA was the most significant prognostic marker in stage II CRC (P = 0.0189). The Cox regression and sensitivity analysis before and after adjusting for PS both revealed elevated early postoperative CEA was the strongest independent prognostic factor of OS, DFS, and CSS (P < 0.001). Survival analysis revealed that patients with elevated early postoperative CEA had lower OS (53.62% VS 84.16%), DFS (50.03% VS 86.75%), and CSS (61.77% VS 90.30%) than patients with normal early postoperative CEA (P < 0.001). When the postoperative CEA was positive, the preoperative CEA level showed no significant effect on the patient's prognosis (all P-values were > 0.05). Patients with a CEA ratio ≤0.55 or CEA absolute value ≤-0.98 had a worse prognosis (all P-values were < 0.001). Survival analysis suggested that adjuvant chemotherapy for stage II CRC patients with elevated early postoperative CEA may improve the CSS (P = 0.040).

Conclusions: Early postoperative CEA was a better biomarker for prognosis of stage II CRC patients than T stage and preoperative CEA, and has the potential to become a high-risk factor to guide the prognosis and treatment of stage II CRC patients.

Keywords: Postoperative serum carcinoembryonic antigen; adjuvant chemotherapy; high-risk factor; prognosis; stage II colorectal cancer.

Figure 1

Study design.

Figure 2

The receiver operating characteristics (ROC) curves of postoperative CEA with respect to CSS.

Figure 3

The receiver operating characteristics (ROC) curves and the area under the curves (AUCs) of postoperative CEA, preoperative CEA, and T stage.

Figure 4

Meta-Analysis estimate postoperative carcinoembryonic antigen (CEA) levels serves as an independent prognostic factor in CRC patients.

Figure 5

Overall survival (OS), disease-free survival time (DFS), and cancer-specific survival (CSS) with respect to postoperative carcinoembryonic antigen (CEA) levels. (A) K-M curves of OS based on postoperative CEA levels. (B) K-M curves of DFS based on postoperative CEA levels. (C) K-M curves of CSS based on postoperative CEA levels. (D) 5-year OS, DFS, and CSS of normal and elevated groups.

Figure 6

Patients’ overall survival (OS), disease-free survival time (DFS), and cancer-specific survival (CSS) based on whether receive adjuvant chemotherapy. (A) K-M curves of OS based on whether receive adjuvant chemotherapy in postoperative CEA-positive patients. (B) K-M curves of DFS based on whether receive adjuvant chemotherapy in postoperative CEA -positive patients. (C) K-M curves of CSS based on whether receive adjuvant chemotherapy in postoperative CEA -positive patients. (D) K-M curves of OS based on whether receive adjuvant chemotherapy in postoperative CEA -negative patients. (E) K-M curves of DFS based on whether receive adjuvant chemotherapy in postoperative CEA -negative patients. (F) K-M curves of CSS based on whether receive adjuvant chemotherapy in postoperative CEA -negative patients. 0, without adjuvant chemotherapy; 1, with adjuvant chemotherapy.

Figure 7

Patients’ overall survival (OS), disease-free survival time (DFS), and cancer-specific survival (CSS) based on different chemotherapy regimens. (A) K-M curves of OS based on different chemotherapy regimens in postoperative CEA-positive patients. (B) K-M curves of DFS based on different chemotherapy regimens in postoperative CEA-positive patients. (C) K-M curves of CSS based on different chemotherapy regimens in postoperative CEA-positive patients. (D) K-M curves of OS based on different chemotherapy regimens in postoperative CEA-negative patients. (E) K-M curves of DFS based on different chemotherapy regimens in postoperative CEA -negative patients. (F) K-M curves of CSS based on different chemotherapy regimens in postoperative CEA -negative patients. 0, without adjuvant chemotherapy; 1, with 3-month adjuvant chemotherapy; 2, with 6-month adjuvant chemotherapy.