Risk Factors of Lymph Node Metastasis in Patients with Pancreatic Neuroendocrine Tumors (PNETs)

BACKGROUND: The prognostic value of lymph node metastasis in patients with PNETs is controversial. Understanding the effect of lymph node metastasis on prognosis in pancreatic neuroendocrine tumors is helpful for surgery and follow-up. The purposes of this study are to identify predictors of lymph node metastasis among patients with PNETs and determine its prognostic associations. METHODS: A retrospective analysis of the surveillance, epidemiology, and end results (SEER) database was performed. Patients with PNETs that underwent surgery and pathologic nodal staging were identified. Logistic regression and Cox regression were performed to identify independent predictors and prognostic factors, respectively. RESULTS: Of 1956 patients (age: 56.8 ± 13.4 years, 53.3% males), 748 (38.2%) had lymph node metastasis. On multivariable analysis, tumor located in pancreas head, distant metastasis, and poorly differentiated, undifferentiated, and unknown differentiated histology grades were three independent risk factors of lymph node metastasis. In the entire cohort, lymph node metastasis indicated a worse overall survival (HR: 1.48, 95% CI: 1.17-1.88, p < 0.001) and disease-specific survival (HR: 1.87, 95% CI: 1.41-2.48, p < 0.001) on multivariable analysis. Lymph node metastasis was associated with worse overall (HR: 1.45, 95% CI: 1.08-1.93, p = 0.012) and disease-specific survival (HR: 2.13, 95% CI: 1.48-3.05, p < 0.001) in patients without distant metastasis on multivariate analysis. Lymph node metastasis was also independently associated with worse disease-specific survival among patients in well differentiation (HR: 2.16, 95% CI: 1.35-3.46, p = 0.001) and moderately differentiation (HR: 2.67, 95% CI: 1.28-5.56, p = 0.009) groups on multivariate analysis. CONCLUSIONS: Tumor located in pancreas head, distant metastasis, and poorly differentiated, undifferentiated, and unknown differentiated histology grades were three independent risk factors for lymph node metastasis. Lymph node metastasis was an independent prognostic factor of worse OS and DSS in patients with tumor located in pancreas head. Lymph node metastasis was an independent prognostic factor of worse OS and DSS in patients without distant metastasis. Lymph node metastasis was an independent prognostic factor of worse DSS in well differentiation and moderately differentiation groups.