Comparison of the current AJCC-TNM numeric-based with a new anatomical location-based lymph node staging system for gastric cancer: A western experience

Abstract

Background: In gastric cancer, the current AJCC numeric-based lymph node staging does not provide information on the anatomical extent of the disease and lymphadenectomy. A new anatomical location-based node staging, proposed by Choi, has shown better prognostic performance, thus soliciting Western world validation.

Study design: Data from 284 gastric cancers undergoing radical surgery at the Second University of Naples from 2000 to 2014 were reviewed. The lymph nodes were reclassified into three groups (lesser and greater curvature, and extraperigastric nodes); presence of any metastatic lymph node in a given group was considered positive, prompting a new N and TNM stage classification. Receiver-operating-characteristic (ROC) curves for censored survival data and bootstrap methods were used to compare the capability of the two models to predict tumor recurrence.

Results: More than one third of node positive patients were reclassified into different N and TNM stages by the new system. Compared to the current staging system, the new classification significantly correlated with tumor recurrence rates and displayed improved indices of prognostic performance, such as the Bayesian information criterion and the Harrell C-index. Higher values at survival ROC analysis demonstrated a significantly better stratification of patients by the new system, mostly in the early phase of the follow-up, with a worse prognosis in more advanced new N stages, despite the same current N stage.

Conclusions: This study suggests that the anatomical location-based classification of lymph node metastasis may be an important tool for gastric cancer prognosis and should be considered for future revision of the TNM staging system.

Fig 1. Disease-free survival rates for each staging system.

(A) Current N stage. Shown are P values for pairwise comparisons of DFS curves in N0 vs. N1, N1 vs. N2, N2 vs. N3a, and N3a vs. N3b. (B) New N stage. Shown are P values for pairwise comparisons of DFS curves in new N0 vs. N1, N1 vs. N2, and N2 vs. N3. (C) Current TNM stage. Shown are P values for pairwise comparisons of DFS curves in different substages. (D) New TNM stage. Shown are P values for pairwise comparisons of DFS curves in different substages. Note to figures 1C and 1D: The iterations required to achieve significant DFS rates among different substages were eleven in the current TNM staging system (IA vs. IB, P = 0.207; IA vs. IIA, P = 0.007; IB vs. IIA, P = 0.060; IB vs. IIB, P < 0.001; IIA vs. IIB, P = 0.154; IIA vs. IIIA, P = 0.002; IIB vs. IIIA, P = 0.069; IIB vs. IIIB, P < 0.001; IIIA vs. IIIB, P = 0.096; IIIA vs. IIIC, P = 0.044; IIIB vs. IIIC, P = 0.433) and eight in the new TNM staging system (IA vs. IB, P = 0.388; IA vs. IIA, P = 0.003; IB vs. IIA, P = 0.006; IIA vs. IIB, P = 0.653; IIA vs. IIIA, P = 0.012; IIB vs. IIIA, P = 0.015; IIIA vs. IIIB, P = 0.046; IIIb vs. IIIC, P = 0.241).

Fig 2. Disease-free survival rates for new N stages.

(A) DFS rates among each combination of anatomical location-based lymph node groups [LC: lesser curvature; GC: greater curvature; EP: extraperigastric nodes]. (B) DFS rates for each new N stage at current N1 stage. Shown are P values for pairwise comparison of DFS curves in new N1 and N2. (C) DFS rates for each new N stage at current N2 stage. Shown are P values for pairwise comparisons of DFS curves in new N1 and N2, and N2 and N3. All curves P < 0.001. (D) DFS rates for each new N stage at current N3 stage. Shown are P values for pairwise comparison of DFS curves in new N2 and N3.

Fig 3. Accuracy of the competing staging systems to predict disease-free survival rate.

(A) Results from bootstrap analysis (1,000 samples). The mean differences in BIC and Harrell C-index with 95% confidence intervals were based on multivariable logistic regression including variables grouped in the best model selected by Cox's analysis. The mean differences in the Area Under the Curve (AUC) for TNM stage and AUC for N stage with 95% confidence intervals were calculated by using the time-dependent receiver-operating-characteristic (ROC) analysis for censored survival data. By these procedures, 95% CIs were computed for differences in the four indices indicating significantly different predictive ability of two staging systems if the zero value was not included. (B) Areas under the ROC curves computed by the time-dependent analysis for censored survival data based on different staging systems according to TNM 7th edition and the new TNM model. Mean AUC values and their 95% CIs were calculated at several time points of follow-up and for each competing system. Error bars represent 95% bootstrap confidence intervals. (C) Analysis of the predictive accuracy of the two competing staging systems through the 5th year of follow-up, computed by the time-dependent ROC analysis for censored survival data.