Influencing factors for lymph node metastasis and prognosis in stage T1 and T2 esophageal squa-mous cell carcinoma after radical surgery and construction of nomogram prediction models / 中华消化外科杂志

ABSTRACT

Objective:To investigate the influencing factors for lymph node metastasis and prognosis in stage T1 and T2 esophageal squamous cell carcinoma after radical surgery and construct nomogram prediction models.Methods:The retrospective cohort study was conducted. The clinico-pathological data of 672 patients with T1 and T2 esophageal squamous cell carcinoma who were admitted to the Affiliated Hospital of North Sichuan Medical College from January 2014 to December 2019 were collected. There were 464 males and 208 females, aged (65±8)years. All patients under-went radical esophagectomy+2 or 3 field lymph node dissection. Observation indicators (1) lymph node dissection, metastasis and follow-up. (2) risk factors for lymph node metastasis of esophageal cancer after radical resection. (3) prognostic factors of esophageal cancer after radical resection. (4) construction and evaluation of the prediction models of lymph node metastasis and prognosis of esophageal cancer after radical resection. Follow-up was conducted using outpatient examination, telephone and internet consultations to detect survival of patients up to April 2021. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Kaplan-Meier method was used to calculate survival rate and draw survival curve. Log-Rank test was used for survival analysis. Logistic regression model was used for univariate and multivariate analyses of risk for lymph node metastasis, and COX regression model was used for univariate and multivariate analyses of prognosis. Based on the results of multi-variate analysis, the nomogram prediction models for lymph node metastasis and prognosis predic-tion were constructed. The prediction discrimination of the nomogram models were evaluated using the area under curve (AUC) of the receiver operating characteristic curve (ROC). The calibration curve was used to evaluate the prediction consistency of the models. Results:(1) Lymph node dissection, metastasis and follow-up. The number of lymph node dissected was 14±8 and the number of lymph node metastasis was 2(range, 1?19) in 672 patients. Of the 672 patients, there were 182 cases had lymph node metastasis, including 58 cases in T1 stage and 124 cases in T2 stage. All 672 patients were followed up for 38 (range, 1?85)months. The average overall survival time of 672 patients was 65 months, with the 1-, 3-, 5-year overall survival rate as 89.0%, 74.3%, 66.0%, respectively. The average overall survival time of 325 patients in T1 stage and 347 patients in T2 stage were 70 months and 61 months. The 1-, 3-, 5-year overall survival rate of 325 patients in T1 stage and 347 patients in T2 stage were 95.0%, 83.5%, 73.4% and 87.4%, 69.9%, 59.2%, respectively, showing a significant difference in survival between them ( χ2=14.51, P<0.05). (2) Risk factors for lymph node metastasis of esophageal cancer after radical resection. Results of univariate analysis showed that tumor location, tumor histological grade, tumor T staging were related factors affecting lymph node metastasis of esophageal cancer after radical resection ( odds ratio=1.40, 1.54, 2.56, 95% confidence interval as 1.07?1.85, 1.20?1.99, 1.79-3.67, P<0.05). Results of multivariate analysis showed that tumor location, tumor histological grade, tumor T staging were independent factors affecting lymph node metastasis ( odds ratio=1.42, 1.61, 2.63, 95% confidence interval as 1.07?1.89, 1.25?2.09, 1.82?3.78, P<0.05). (3) Prognostic factors of esophageal cancer after radical resection. Results of univariate analysis showed that preoperative comorbidities, postoperative complications, tumor histological grade (G3), tumor T staging, tumor N staging (N1 stage, N2 stage, N3 stage), tumor TNM staging (Ⅲ stage, Ⅳ stage) were related factors affecting prognosis of esophageal cancer after radical resection ( hazard ratio= 1.48, 1.64, 2.23, 1.85, 2.09, 4.48, 4.97, 3.54, 5.53, 95% confidence interval as 1.08?2.03, 1.20?2.23, 1.47?3.39, 1.34?2.54, 1.44?3.04, 2.89?6.95, 1.57?15.73, 2.48?5.05, 1.73?17.68, P<0.05). Results of multivariate analysis showed that preoperative comorbidities, G3 of tumor histological grade, T2 stage of tumor T staging, N1 stage, N2 stage, N3 stage of tumor N staging were independent risk factors affecting prognosis of esophageal cancer after radical resection ( hazard ratio=1.57, 1.89, 1.63, 1.71, 3.72, 3.90, 95% confidence interval as 1.14?2.16, 1.23?2.91, 1.17?2.26, 1.16?2.51, 2.37?5.83, 1.22?12.45, P<0.05). (4) Construction and evaluation of the prediction models of lymph node metastasis and prognosis of esophageal cancer after radical resection. Based on the results of multivariate analysis, tumor location, tumor histological grade, tumor T staging were applied to construct a nomo-gram model for lymph node metastasis prediction of esophageal cancer after radical resection, the score of tumor location, tumor histological grade, tumor T staging were 82, 100, 100, respectively, and the sum of the scores corresponding to the lymph node metastasis rate. Preoperative comor-bidity, tumor histological grade, tumor T staging, tumor N staging were applied to construct a nomo-gram model for 1-, 3-, 5-year overall survival rate prediction of esophageal cancer after radical resection, the score of preoperative comorbidity, tumor histological grade, tumor T staging, tumor N staging were 23, 38, 27, 100, respectively, and the sum of the scores corres-ponding to the 1-, 3-, 5-year overall survival rate. Results of ROC showed that the AUC of nomogram model for lymph node metastasis prediction after radical esophagectomy was 0.66 (95% confidence interval as 0.62?0.71, P<0.05). The AUC of nomogram model for 1-, 3-, 5-year overall survival rate prediction after radical esophagectomy were 0.73, 0.74, 0.71 (95% confidence intervals as 0.66?0.80, 0.68?0.79, 0.65?0.78, P<0.05). Results of calibration curve showed that the predicted lymph node metastasis rate and the predicted 1-, 3-, 5-year overall survival rate by nomogram models were consistent with the actual lymph node metastasis rate and 1-, 3-, 5-year overall survival rate. Conclusions:Tumor location, tumor histological grade, tumor T staging are independent factors affecting lymph node metastasis in T1 and T2 esophageal squamous cell carcinoma after radical surgery and nomogram model constructed by these indicators can predict the lymph node metas-tasis rate. Preoperative comor-bidities, G3 of tumor histological grade, T2 stage of tumor T staging, N1 stage, N2 stage, N3 stage of tumor N staging are independent risk factors affecting prognosis and nomogram model constructed by these indicators can predict the overall survival rate of patients after surgery.