Incorporation of Extranodal Metastasis of Gastric Carcinoma into the 7th Edition UICC TNM Staging System

BACKGROUND To assess the clinical significance and prognostic impact of extranodal metastasis (EM) in gastric carcinoma and establish an optimal classification in the staging system. METHODOLOGY/PRINCIPAL FINDINGS A total of 1343 patients with gastric carcinoma who underwent surgical resection were recruited to determine the frequency and prognostic significance of EMs. EMs were divided into two groups (EM1 and EM2) and then incorporated into the 7(th) edition UICC TNM staging system. EMs was detected in 179 (13.3%) of 1343 patients who underwent radical resection. Multivariate analysis identified EMs as an independent prognostic factor (HR = 1.412, 95%CI = 1.151-1.731, P<0.001). After curative operation, the overall survival rate were worse in patients with ≥3 cases of EM (EM2) than those with the number of 1 and 2 cases (EM1) (P<0.001). Survival of patients with EM1 was found almost comparable to that of N3 stage (P = 0.437). Survival of patients with EM2 showed similar to that of stage IV patients (P = 0.896). By using the linear trend X(2), likelihood ratio X(2), and Akaike information criterion (AIC) test, EM1 treated as N3 stage and EM2 treated as M1 stage performed higher linear trend X(2) scores, likelihood ratio X(2) scores, and lower AIC value than the 7(th) edition UICC TNM staging system, which represented the optimum prognostic stratification, together with better homogeneity, discriminatory ability, and monotonicity of gradients. CONCLUSIONS/SIGNIFICANCE EMs might be classified based on their number and prognostic information and should incorporate into the TNM staging system.