The ratio between metastatic and examined lymph nodes (N ratio) is an independent prognostic factor in gastric cancer regardless of the type of lymphadenectomy: results from an Italian multicentric study in 1853 patients

Abstract

Purpose: To investigate whether the ratio between metastatic and examined lymph nodes (N ratio) is a better prognostic factor as compared with traditional staging systems in patients with gastric cancer regardless of the extension of lymph node dissection.

Patients & methods: We retrospectively reviewed the data of 1853 patients who underwent radical resection for gastric carcinoma at 6 Italian centers. Patients with >15 (group 1, n = 1421) and those with <or=15 (group 2, n = 432) lymph nodes examined were separately analyzed. N ratio categories (N ratio 0, 0%; N ratio 1, 1%-9%; N ratio 2, 10%-25%; N ratio 3, >25%) were determined by the best cut-off approach.

Results: After a median follow-up of 45.5 months (range, 4-182 months), the 5-year overall survival of N0, N1, and N2 patients of group 1 versus group 2 was 83.4% versus 74.2% (P = 0.0026), 54.3% versus 44.3% (P = 0.018), and 32.7% versus 14.7% (P = 0.004), respectively, suggesting that a low number of excised lymph nodes can lead to the understaging of patients. N ratio identified subsets of patients with significantly different survival rates within N1 and N2 stages in both groups. At multivariate analysis, the N ratio (but not N stage) was retained as an independent prognostic factor both in group 1 and group 2 (HR for N ratio 1, N ratio 2, and N ratio 3 = 1.67, 2.96, and 6.59, and 1.56, 2.68, and 4.28, respectively). In our series, the implementation of N ratio led to the identification of subgroups of patients prognostically more homogeneous than those classified by the TNM system.

Conclusion: N ratio is a simple and reproducible prognostic tool that can stratify patients with gastric cancer also in case of limited lymph node dissection. These data may represent the rational for improving the prognostic power of current UICC TNM staging system and ultimately the selection of patients who may most benefit from adjuvant treatments.

FIGURE 1. Overall survival curves for different N ratio among N1 (upper panel) and N2 (lower panel) patients with more than 15 lymph node resected.

FIGURE 2. Comparison of prognostic discrimination power between the traditional (TNM) and N ratio based (TRM) staging systems. To this aim, we considered the overall survival data of all our patients (n = 1853). When the 6 TNM stages were plotted against their respective HR ranges, significant overlapping was observed among all stages, with the exception of stage IA (upper panel). K-means cluster analysis identified 6 prognostically homogeneous TRM classes: when the 6 TRM stages were plotted against their respective HR ranges, no overlapping was observed (lower panel).