A modified subclassification to evaluate the survival of patients with N3 gastric cancer: an international database study

BACKGROUND: The eighth TNM classification for gastric cancer categorizes N3 as N3a and N3b in the final pathologic stage. The cutoff for N3a/N3b is defined as 15 metastatic lymph nodes, but the rationale for this cutoff remains unclear. This study aimed to determine the optimal N3a/N3b cutoff and evaluate its prognostic significance. METHODS: An international database was constructed by combining data from patients with N3 gastric cancer and complete five-year follow-up data from the Surveillance, Epidemiology, and End Results program database (n = 1833) and the Fujian Medical University Union Hospital database (n = 920) (total n = 2753). A log-rank test was performed to determine the optimal N3a/N3b cutoff, and its prognostic significance was confirmed in a two-step multivariate analysis and compared to that of the eighth TNM. RESULTS: A cut-point analysis performed at each metastatic lymph node number identified the greatest survival difference between N3a and N3b at 13 metastatic lymph nodes (χ(2) = 157.671, P = 3.65 × 10(− 36)). In patients with 14–15 metastatic lymph nodes, prognoses were significantly worse than those in patients with 7–13 metastatic lymph nodes (P < 0.001) but similar to those in patients with > 15 metastatic lymph nodes (P = 0.078). Therefore, patients with 14–15 metastatic lymph nodes were incorporated into a modified N3b classification. In the two-step multivariate analysis, the eighth N3 classification fell out of the model, while the modified N3 classification remained intact (HR 1.51, P < 0.001). Further analyses demonstrated that the modified TNM classification had superior homogeneity, discriminatory ability, and gradient monotonicity compared to the eighth TNM classification. CONCLUSIONS: For improved prognostic stratification, we recommend adjusting the cutoff for subclassification of N3 gastric cancer to 13 metastatic lymph nodes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-018-5187-7) contains supplementary material, which is available to authorized users.