Construction And Clinical Application Of A New Tumor Staging System For Lymph Node-negative Gastric Cancer Based On Recursive Partitioning Analysis

Objective:This study aimed to determine the predictive risk factors affecting the prognosis of patients with lymph node-negative gastric cancer,and then constructed a new tumor staging system using recursive partitioning analysis(RPA).On this basis,we investigated the value of the RPA staging system in prognosis prediction in patients with lymph node-negative gastric cancer.Methods:A retrospective study was performed on the clinicopathological data of 713 patients with lymph node-negative gastric cancer who underwent radical gastrectomy in Northern Jiangsu people's Hospital affiliated to Yangzhou University from July 2012 to July 2018.Cox univariate and multivariate logistic regression analyses were performed to analyze 14 clinicopathological factors,including age,sex,tumor location,tumor size,degree of differentiation,macro-type,pT stage,lymphovascular invasion,neural invasion,ulcer,mode of surgery,number of Examined Lymph Nodes,chemotherapy and AJCC tumor-node-metastasis(TNM)stages.Kaplan-Meier(K-M survival analysis was used to create the survival plots,the log-rank test was used to compare the survival difference among groups and independent factors affecting the prognosis of patients with lymph node-negative gastric cancer were identified.With recursive partitioning analysis(RPA),the data set was stratified into different categories,and a new RPA staging system based on outcome events was established-RPA tumor staging system.Chi-square test,Akaike information criterion(AIC),and Harrell's concordance index(C-index)were used to evaluate the discriminative power of the staging systems(RPA vs AJCC-TNM).Finally,the new staging system was further validated by using the clinicopathological data of 500 patients with lymph node-negative gastric cancer treated in the affiliated Hospital of Yangzhou University from January 2012 to January 2018.Results:The 5-year overall survival(OS)rates of the patients with 8th AJCC-TNM stage IA-?B in the training set were IA 82.1%,IB 67.2%,IIA 66.8%,?B 53.1%(IA vs IB:p=0.06,IA vs ?A:p<0.01,IA vs ?B:p<0.01,IB vs ?A:p=0.5,?A vs ?B:p=0.04),respectively.Univariate analysis showed that age,tumor size,number of Examined Lymph Nodes,neural invasion,lymphovascular invasion,the degree of differentiation and the depth of tumor invasion correlated with the prognosis of patients with lymph node-negative gastric cancer(p<0.05).Further multivariate analysis indicated that age,nerve invasion,depth of tumor invasion and the number of lymph node biopsy were independent predictors of survival in patients with lymph node-negative gastric cancer(p<0.05).Finally,a new staging system was established using age,nerve invasion,and pT staging as the descriptors through RPA.The patients were stratified into stages RPA I,RPA II,and RPA ? according to the regression tree assignment,and the 5-year OS rates for the corresponding RPA stages were 84%,65.6%,and 46.2%,respectively(p<0.001).Multivariate stepwise logistic regression analysis showed that the RPA stage was predictive of prognosis in patients with lymph node-negative gastric cancer.Compared with the 8th AJCC-TNM staging system of gastric cancer,the AIC value of the RPA staging system was lower(1577.892 vs 1606.59),with a higher chi-square value(54.85 vs 31.51,p<0.001),and a higher C index(0.775 vs 0.715,p<0.01),indicating better homogeneity,improved prognostic stratification and increased discriminatory power of the system.In addition externally validation demonstrated that RPA staging system had obvious advantages over the 8th AJCC-TNM staging system(RPA staging system vs 8th AJCC-TNM staging system:AIC1244.835 vs 1288.385;chi-square value 75.02 vs 58.77,p<0.001;Cindex 0.876 vs 0.844,p<0.01)Conclusions:A RPA-based staging system has been successfully constructed and validated,demonstrating superiority over the 8th edition AJCC-TNM gastric cancer staging system.The external validation of the new staging system through external data sets further shown that the new staging system is helpful to improve the accurate assessment of the prognosis of lymph node-negative gastric cancer and provide guidance for appropriate treatment.