The baseline characteristics of the 157 Siewert type II AEG patients are shown in Table 1. There were 111 (70.7%) males and 46 (29.3%) females. The median age was 62 years, ranging from 33 ~ 83 years. The median tumor size was 4.5 cm (range, 1.3 ~ 12.0 cm). With respect to surgery, 98 patients underwent curative proximal gastrectomy, and 59 patients underwent total gastrectomy. According to histopathological grading, well and moderately differentiated tumors were observed in 94 (59.9%) patients, and poorly differentiated or undifferentiated tumors were observed in the remaining 63 (40.1%) patients. The mean and median total number of lymph nodes examined (TLNE) were 18.6 and 17.0, respectively, with a range of 1–64 and a standard deviation (SD) of 10.7. There were 115 (73.2%) patients with LN metastasis, and 42 (26.8%) were free of nodal disease. The median LNR of the entire population was 0.16. The LODDS values ranged from − 2.11 to 1.61, with a median value of -0.56. In the Kaplan-Meier analysis, age, histological grade, TNM pT stage, tumor size, lymphovascular invasion, TNLE and each of the LN staging systems were significantly correlated with OS.
The median follow-up time for all patients was 42 months. The 5-year OS rate for the whole group of patients was 39.5%, and the median OS time was 42 months. The Kaplan-Meier curves of the OS of patients according to the TNM pN stage, LNR, and LODDS score are shown in Fig. 1. For the TNM pN staging system, the 5-year OS rates were 69.0%, 32.6%, 41.2%, and 11.4%, respectively (P < 0.001). For the LNR staging system, the 5-year OS rates were 69.0%, 44.4%, 46.5%, and 9.3%, respectively (P < 0.001). For the LODDS staging system, the 5-year OS rates were 70.8%, 56.0%, 35.8%, and 7.4%, respectively (P < 0.001) (Table 1). However, the survival curves of each LN staging system overlapped. Patients in pN1 stage had higher survival rates than patients in pN2 stage. One possible explanation for this finding is that some pN2 patients were incorrectly staged as pN1 due to an insufficient TLNE, which is defined as stage migration. All of the variables that were statistically significant in the univariate survival analysis were entered into the multivariate survival analysis.
Performance of the LN classification systems
Through Cox regression modeling, the LN staging system with the best prognostic discriminatory ability was assessed through iterative statistical models and through the comparison of C-index and AIC values. The TNM pN stage, LNR and LODDS systems all showed significant prognostic value in the multivariate Cox regression analyses. When assessed as categorical variables, the LNR staging system had a better prognostic performance (C-index: 0.752; AIC: 926.350) than the AJCC 8th edition (C-index: 0.740; AIC: 934.349) and LODDS (C-index: 0.737; AIC: 939.087) staging systems. When stratified by the TLNE, the LNR remained the best performing model among patients with less than 16 retrieved LNs (C-index: 0.810; AIC: 352.293). When LN status was modeled as a continuous variable, the LODDS scoring system (C-index: 0.729; AIC: 940.483) outperformed other scoring systems, including the LNP (C-index: 0.721; AIC: 946.935) and LNR (C-index: 0.725; AIC: 938.918) (Table 3). However, among patients with less than 16 LNs examined, the LNP system performed the best (C-index: 0.809; AIC: 350.265).
The results of Spearman's correlation analyses are shown in Table 3. We found that both the LNP (r = 0.198 P = 0.013) and LODDS (r=-0.234 P = 0.003) values correlated with the TLNE. However, no significant correlations between the LNR and TLNE were observed. There were significant and positive correlations between the LNR and LNP (r = 0.927 P = 0.000), between the LODDS score and LNP (r = 0.887 P = 0.000), and between the LODDS score and LNR v (r = 0.965 P = 0.000).
We created scatter plots to explain the relationship between the LNR and LODDS score. As shown in Fig. 2, the LODDS value increased with the LNR, indicating a close correlation. However, when the LNR was close to 0 or 1, the LODDS system was able to efficiently distinguish heterogeneity. The relation of the TNM pN stage, LNR and LODDS staging systems differs according to the TLNE (Fig. 3). The LNR staging system includes stages 1–4 for 6 LNs examined, and there is no stage 1 in the LODDS system for less than 16 LNs examined. The LODDS classification in stage 3 has 24 LNs examined 3–13 metastatic LNs examined and 3–9 metastatic LNs by 16 LNs examined. Therefore, the LODDS system does not perform well with a relatively large TLNE.