Implication of perineural invasion in patients with stage II gastric cancer

The clinicopathological characteristic of the whole cohort

​A total of 233 eligible patients with stage II GC were included in this study (Fig. 1), and the clinical and pathological characteristics of all patients are summarized in Table 1. There were 75 women (32.19%) and 158 men (67.81%). The mean age was (59.04 ± 12.68) years old (range, 21–89 years). One hundred and nine (46.78%) patients underwent total gastrectomy, and 124 (53.22%) patients underwent partial gastrectomy. AC was administered in 158 (67.81%) patients. On pathological examination, 135 (57.94%) patients had stage IIA disease, and 98 (42.06%) patients had stage IIB disease. There were 100 (42.92%) patients with PNI and 133 (57.08%) patients without PNI. In addition, vascular invasion was present in 50 (21.46%) patients, and lymph node metastasis was present in 114 (48.93%). The median follow-up time was 51.0 months. During follow-up, 65 (27.90%) patients relapsed or deceased. The OS were 97.0%, 83.3%, and 73.1% at 1, 3, and 5 years, respectively, while the DFS were 95.7%, 80.8%, and 67.5% at 1, 3, and 5 years, respectively.

Table 1 Relationship between PNI and clinicopathological features in stage II GCAssociation between PNI and clinical pathological features

Compared with patients without PNI, patients with PNI were younger and were more likely to have more advanced T stage, poor tumor differentiation, lower rate of lymph node metastasis, and a higher proportion of diffuse type or mixed type (p < 0.05) by Lauren’s classification. There were no differences between the two groups in tumor location, CEA, tumor diameter, vascular invasion, and TNM stage (p > 0.05). Types of procedure and use of AC were similar (p > 0.05). Patients with PNI were more likely to develop peritoneal metastases (52.94% vs 16.13%, P = 0.038, Supplementary Table1).

Comparison of OS and DFS between different PNI groups

Kaplan–Meier curve analysis was performed to explore the role of PNI in patients with stage II GC. The OS and DFS for patients with PNI were significantly lower than that for patients without PNI (p = 0.019 and p = 0.032, respectively) (Fig. 2).

Fig. 2figure 2

Survival curve analysis showed that the patients with PNI had worse OS (a. p = 0.019) and DFS (b. p = 0.032) than those without PNI

Univariate and multivariate analyses for OS and DFS

According to univariate analysis, age, CEA, PNI, tumor location, AC, and T stage were associated with OS in patients with stage II GC (Table 2). The variables for the multivariate analysis were selected from the univariate analysis when p < 0.1. Multivariate analysis showed that CEA > 5 ng/mL (HR = 2.20, 95% CI 1.17–4.17, p = 0.015), the presence of PNI (HR = 1.76, 95% CI 1.02–3.06, p = 0.044), and tumor located in the middle stomach (HR = 3.19, 95% CI 1.62–6.26, p < 0.001) were associated with poor OS, while AC (HR = 0.51, 95% CI 0.30–0.88, p = 0.016) was associated with better OS (Table 2).

Table 2 Univariate and Multivariate analysis for predictors of overall survival

In addition, Cox regression analysis was performed to determine the potential value of PNI for DFS. Multivariate analysis indicated that the presence of PNI (HR = 1.70, 95% CI 1.04–2.80, p = 0.035), middle of the stomach (HR = 3.26, 95% CI 1.73–6.14, p < 0.001) and CEA > 5 ng/ml (HR = 2.34, 95% CI 1.30—4.21, p = 0.005) were associated with poor DFS, while AC (HR = 0.52, 95% CI 0.31–0.86, p = 0.011) was associated with better DFS (Table 3).

Table 3 Univariate and Multivariate analysis for predictors of disease-free survivalCorrelation between PNI and benefit of AC

Among patients with stage II GC, patients who received AC had a better prognosis for DFS than those who did not (p = 0.046, Fig. 3b), but there was no difference between the two groups in OS (p = 0.052, Fig. 3a). Therefore, we analyzed whether patients with PNI or without PNI could benefit from AC. Among the patients with PNI, patients who received AC had better OS than those who did not receive AC (p = 0.022, Fig. 3c) and DFS(p = 0.027, Fig. 3d).​ Among patients without PNI, there was no significant difference between patients who received AC and those who did not in OS (p = 0.564, Fig. 3e) and DFS (p = 0.470, Fig. 3f), which means patients without PNI were associated with well prognosis. Of note, patients with PNI and receiving AC had a similar OS (p = 0.603, Fig. 4a) and DFS (p = 0.745, Fig. 4b) to those who did not receive AC and in the absence of PNI.

Fig. 3figure 3

Survival curve analysis showed that patients undergoing AC had similar OS (a. p = 0.052) and better DFS (b. p = 0.046) than those who did not undergo AC. For the patients with PNI, the patients who underwent AC had better OS (c. p = 0.022) and DFS (d. p = 0.027) than those who did not undergo AC. For the patients without PNI, the OS (e. p = 0.564) and DFS (f. p = 0.47) of patients with PNI and who did not undergo AC were similar

Fig. 4figure 4

Survival curve analysis showed that patients with PNI and undergoing AC had similar OS (a. p = 0.603) and DFS (b. p = 0.745) to those absence of PNI and no AC

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