Relationship Between Tumor Maximum Diameter And Preoperative Carcinoembryonic Antigen Level And Prognosis Of Stage Ⅰ-Ⅲ Colon Cancer Patients

Objective The aim of this study was to investigate the effect of tumor size and preoperative carcinoembryonic antigen level on the prognosis of patients with stage Ⅰ-Ⅲ colon cancer,and whether the combination of tumor size and preoperative CEA level with AJCC stage can improve the ability of AJCC stage to predict the prognosis of patients with stage Ⅰ-Ⅲ colon cancer,and ultimately become an additional index to guide clinical practice in AJCC stage.Methods The clinical data of stage Ⅰ-Ⅲ colon cancer patients who underwent radical surgery from January 2010 to December 2015 in SEER database were retrospectively analyzed.According to the preoperative CEA level,patients were divided into the normal group(≤5.0ng/ml)and the elevated group(>5.0ng/ml).The patients were divided into the small diameter group,the medium diameter group and the large diameter group by using X-tile software.Kaplan-Meier method was used to estimate the cancer specific survival(CSS).Log-rank test was used to evaluate the survival difference.Cox regression model was used to analyze the prognostic effect of tumor size and preoperative CEA level on stage Ⅰ-Ⅲ colon cancer patients.In order to explore whether the impact of tumor size and preoperative CEA level on CSS was caused by the confounding of hierarchical factors,and to explore whether the size and direction of the effect value(HR)between different levels are stable,we conducted a stratified analysis and draw a forest plot.The nomogram prediction model of AJCC stage and AJCC stage combined with tumor size and preoperative CEA level was established respectively,then we draw the time dependent ROC curve and calculated the AUC to evaluate the discrimination of the model.Finally,the clinical data of patients who underwent colon cancer radical resection in gastrointestinal surgery of Shenzhen Second People’s Hospital from January 2016 to December 2019 were retrospectively analyzed to validate this model externally.Results A total of 17921 patients were included,8825 males(49.24%)and 9096 females(50.76%),11467 patients(64.0%)with normal preoperative CEA level and 6454 patients(36.0%)with elevated CEA level.The tumor size was divided to three groups by using X-tile software,and the cut-off values were 2.7cm and 7.9cm respectively,including 3770 patients(21.04%)in the small diameter group,11979 patients(21.04%)in medium diameter group and 2172 patients(12.12%)in the large diameter group.The median follow-up time was 45 months(IQR,29-66)and 2910 patients(16.24%)died of colon cancer during the last follow-up.The overall 5-year cancer specific survival rate was 81.48%(95%CI,80.82%-82.14%).The 5-year CSS rate of patients with elevated CEA level was 72.75%(95%CI,71.4-8%-74.03%),and that of patients with normal CEA level was 86.25%(95%CI,85.52%-86.98%),the difference was statistically significant(P<0.0001).The 5-year cancer specific survival rate was 90.01%(95%CI,88.91%-91.12%)in the small diameter group,80.37%(95%CI,79.54%-81.20%)in the medium diameter group,and 72.53%(95% CI,88.91%-91.12%)in the large diameter group,the difference was statistically significant(P<0.0001).Multivariate Cox regression analysis showed that elevated preoperative CEA level and larger tumor size were independently associated with shorter CSS.The AUC of AJCC stage combined with tumor size and preoperative CEA level nomogram prediction model was higher than that of AJCC stage model alone,AJCC stage combined with tumor size model and AJCC stage combined with preoperative CEA level model(0.72 vs 0.68 vs 0.70 vs 0.71).In the external validation of the model,the AUC of AJCC stage model combined with tumor size and preoperative CEA level was larger than that of AJCC stage model alone(0.71 vs0.67),which was consistent with the results obtained from the SEER database.Conclusion Elevated preoperative CEA level and larger tumor size are independent risk factors for poor prognosis of stage Ⅰ-Ⅲ colon cancer patients undergoing radical resection.The combination of tumor size and preoperative CEA level with AJCC stage of colon cancer can improve the predictive ability of AJCC stage for the prognosis of patients with stage Ⅰ-Ⅲ colon cancer undergoing radical resection,which can help the hierarchical management and individualized monitoring of patients with stage Ⅰ-Ⅲ colon cancer,and are expected to become the additional index to guide the clinical practice in AJCC stage.