The overall incidence of gastric cancer has decreased over the last few years. Some Japanese studies suggested that it could be due to changes in dietary habits, keeping foods refrigerated, and a decrease in the incidence of H. pylori infection [14]. The mortality rate of gastric cancer has also declined because of early diagnosis, early treatment, and the advancement of operation technique [4]. However, the prognosis of gastric cancer is still dismal. Therefore, the prediction of prognostic factors plays a very important role in the treatment of patients with gastric cancer. Among the well-known prognostic factors for gastric cancer [3, 4, 8, 15–18], depth of tumor invasion, and LN metastasis are the most important independent prognostic factors [3–5, 7]. Status of LN metastasis is categorized by two systems. The first one originated in Japan in the 1980s. This system defines N stage by location of LN metastasis relative to the primary tumor according to the Japanese Classification of Gastric Carcinoma (JCGC) [10]. The other one, based on the number of metastatic LNs, was suggested by Union Internationale Contra le Cancer (UICC), 5th edition, in 1997 [12–19]. TNM classification for malignancy was developed by Pierre Denoix between 1943 and 1952 [2]. In case of gastric cancer, it was first included in the TNM classification in 1966. Before the fifth edition, N classification for gastric cancer was based on the anatomic location of metastatic LNs [4, 11]. However, in the 5th UICC classification, N status was categorized according to the number of metastatic LNs [20]. Many studies reported that UICC N stage, which is based on the number of metastatic LNs, was superior to the JCGC in terms of feasibility, objectivity, and reproducibility and for the accuracy of prognostic prediction [21, 22]. The defined 5th UICC N classification was as follows: N0 (no regional LN metastasis), N1 (metastases in 1–6 LNs), N2 (metastases in 7–15 LNs), and N3 (metastases in ≥16 LNs) [12]. In the 6th edition of the UICC classification, there was no change in N classification. The TNM classification requires at least 15 harvested LNs for accurate staging. Because of this, there were some studies on the ratio of metastatic lymph nodes (based on the number of positive LNs divided by the number of examined LNs) for preventing the stage migration phenomenon [23, 24]. Kim et al. [18] also showed that the N ratio was an independent prognostic factor and reported that it had more comprehensive and precise prognostic value than the number of involved or resected LNs when radical LN dissection was performed. However, more studies will be necessary in this area as well [25].
Recently, the introduction of the 7th edition UICC TNM classification for gastric cancer has made several changes from the 5th/6th edition. According to the new classification, T stage was classified to T1a (lamina propria invasion), T1b (submucosa invasion), T2 (muscularis propria invasion), T3 (subserosa invasion), T4a (serosa invasion), and T4b (adjacent organ invasion). The 7th UICC N stage was redefined as follows: N0 (no regional lymph node metastasis), N1 (metastases in 1–2 LNs), N2 (metastases in 3–6 LNs), N3a (metastases in 7–15 LNs), and N3b (metastases in ≥16 LNs) [13].
Actually, the suitability of the 5th/6th UICC N classification and its necessity of N classification modification had been suggested by some investigators prior to the introduction of the 7th edition UICC TNM classification [25, 26]. The authors from Japan reported that the relative risk for pN3 was not significantly higher than for pN2 in their study, and there was difficulty defining cutoff points in a number-based classification [27]. In the study of Huang et al. [26], they demonstrated that the 6th UICC N classification was not suitable for early gastric cancer and suggested N0 (no regional LN metastasis), N1 (metastases in 1–3 LNs), N2 (metastases in 4–6 LNs), and N3 (metastases in ≥7 LNs) as a new N classification. Deng et al. [25] also reported the necessity of N classification modification and redesigned cutoffs of the number of metastatic lymph nodes.
In order to determine which one is a more effective classification method between the 7th UICC N and the 5th/6th UICC N, we analyzed 295 patients who underwent curative gastrectomy by a single, well-experienced surgeon to determine the superiority of the 7th UICC N classification and other prognostic factors. In univariate analysis, significant prognostic factors were the tumor size, tumor location, the 7th UICC T stage, the 6th UICC N stage, and the 7th UICC N stage. However, the multivariate analysis result showed that the 7th UICC T and N stage were significantly independent prognostic factors (Table 3). Survivals according to the 7th UICC N stage were more evenly distributed than survivals according to the 5th/6th UICC N stage (Figs. 1, 2). Yang et al. [28] also reported that the 7th UICC T and N stages were more evenly distributed than the 6th UICC T and N stages. Deng et al. [9] reported the superiority of the 7th UICC N stage, based on the evidence of the significant difference of 5-year survival rate between N1 and N2 substages of the 7th UICC N stage and no significant prognostic difference between N2 and N3 substages of the 5th/6th UICC N stage. They argued N2 and N3 substages of the 5th/6th UICC N classification should be integrated into only one substage as N3 instead of N3a and N3b in the 7th UICC N classification. However, in our study, there was a significant difference in the 5-year survival rate between the 7th UICC N3a and N3b. And several data indicated there was a significant difference in survivals between N2 and N3 in the 6th N classification [4, 21, 29]. But in the 7th UICC edition, this difference was not reflected in the gastric cancer stage, and it seems that there should be a compensation for this problem.