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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.

SUBMITTER: Fenqi D

PROVIDER: S-EPMC8786716 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceGuidelines recommend measuring preoperative carcinoembryonic antigen (CEA) in patients with colon cancer. Although persistently elevated CEA after surgery has been associated with increased risk for metastatic disease, prognostic significance of elevated preoperative CEA that normalized after resection is unknown.ObjectiveTo investigate whether patients with elevated preoperative CEA that normalizes after colon cancer resection have a higher risk of recurrence than patients with normal preoperative CEA.Design, setting, and participantsThis retrospective cohort analysis was conducted at a comprehensive cancer center. Consecutive patients with colon cancer who underwent curative resection for stage I to III colon adenocarcinoma at the center from January 2007 to December 2014 were identified.ExposuresPatients were grouped into 3 cohorts: normal preoperative CEA, elevated preoperative but normalized postoperative CEA, and elevated preoperative and postoperative CEA.Main outcomes and measuresThree-year recurrence-free survival (RFS) and hazard function curves over time were analyzed.ResultsA total of 1027 patients (461 [50.4%] male; median [IQR] age, 64 [53-75] years) were identified. Patients with normal preoperative CEA had 7.4% higher 3-year RFS (n = 715 [89.7%]) than the combined cohorts with elevated preoperative CEA (n = 312 [82.3%]) (P = .01) but had RFS similar to that of patients with normalized postoperative CEA (n = 142 [87.9%]) (P = .86). Patients with elevated postoperative CEA had 14.9% lower RFS (n = 57 [74.5%]) than the combined cohorts with normal postoperative CEA (n = 857 [89.4%]) (P = .001). The hazard function of recurrence for elevated postoperative CEA peaked earlier than for the other cohorts. Multivariate analyses confirmed that elevated postoperative CEA (hazard ratio [HR], 2.0; 95% CI, 1.1-3.5), but not normalized postoperative CEA (HR, 0.77; 95% CI, 0.45-1.30), was independently associated with shorter RFS.Conclusions and relevanceElevated preoperative CEA that normalizes after resection is not an indicator of poor prognosis. Routine measurement of postoperative, rather than preoperative, CEA is warranted. Patients with elevated postoperative CEA are at increased risk for recurrence, especially within the first 12 months after surgery.

Project description:Background: Carcinoembryonic antigen (CEA) is the most common serum tumor marker in colorectal cancer (CRC). Nevertheless, few previous studies demonstrated the impacts of postoperative CEA and post-preoperative CEA increment on prognosis of CRC. Methods: Patients with stage II and III CRC were included from January 2009 to December 2015. All clinical and follow-up data were collected. Patients were divided into four different groups according to the levels of postoperative serum CEA and post-preoperative CEA trends. Chi-square test was used to analyze the relationship between clinical variables and categorized postoperative CEA and CEA increment. Cox proportional hazard regression was used for univariate and multivariable analyses. The log-rank test was performed to compare PFS and OS among groups. Results: Patients, 1,008, who underwent radical surgery, were enrolled. Our results showed that positive postoperative CEA and CEA increment were related to clinical stage, T stage, N stage, tumor differentiation, and lymphatic invasion (p < 0.05). Univariate and multivariable analysis results suggested that positive postoperative CEA and CEA increment were independent prognostic factors for PFS (HR = 3.149, 95% CI, 2.426-4.088, p = 0.000 for postoperative CEA; HR = 2.708, 95% CI, 2.106-3.482, p = 0.000 for CEA increment) and OS (HR = 3.414, 95% CI, 2.549-4.574, p = 0.000 for postoperative CEA; HR = 2.373, 95% CI, 1.783-3.157, p = 0.000 for CEA increment). The survival analyses revealed positive postoperative CEA, and CEA increment predicted worse prognosis. Furthermore, our results indicated that the 3- and 5-year PFS rates were 86.6 and 78.4% in group A, but decreased to 25.3 and 7.2% in group D (p < 0.001). Similarly, the 3- and 5-year OS rates for group A were 92.5 and 83.9%, much higher than group D (p < 0.001). In other words, patients with both postoperative CEA elevation and CEA increment had the worst prognosis. Conclusions: Positive postoperative CEA and CEA increment were independent prognostic factors for stage II and III CRC. Additionally, postoperative CEA and CEA increment had significant impacts on PFS and OS of CRC.