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Background: Currently, staging for pancreatic neuroendocrine tumors (PNET) considers tumor size, lymph node status, and histologic differentiation. However, the predictive value of these factors as related to overall survival (OS) remains unclear. This study reviews predictors of lymph node (LN) metastases and the impact on survival for resected PNET.
Methods: A prospectively maintained database of patients treated for PNET was reviewed. Patients undergoing surgical resection without evidence of metastatic disease at time of resection were included in this analysis. Chi-Square Test was used to compare categorical variables and LN metastases, and Wilcoxon Rank Sum Test was used for continuous variables, both with the exact method using Monte Carlo estimation. Univariate and multivariate analysis was performed with Cox proportional hazard models and survival calculated with Kaplan Meier curves.
Results: From 1999-2012, 150 patients underwent surgical resection for PNET. The majority (53%) were male, with a median age of 56 years (range 17-82). Incidentally discovered PNET was the most common presentation (42%), followed by abdominal pain (32%). Tumors were uncommonly functional (7%). Distal pancreatectomy was performed in 58%; pancreaticoduodenectomy in 29%, and enucleation in 7%. Of 113 (75%) patients with LN data available for review, 32 (28%) had positive LN (LN+). Both age and lymph node retrieval differed in the LN negative (LN 0) vs. LN+ group, with younger median age (53 years) and higher median LN count (9 vs. 6) in the LN+ group, p=0.05 and p=0.04, respectively. Univariate analysis showed gender, race, clinical presentation, surgery type, and tumor size was not predictive of LN+. Presence of perineural (p=0.016) and lymphovascular (p<0.001) invasion, however, was more common in LN+. With multivariate analysis, only poor/moderate differentiation predicted LN+, with an odds ratio of 7.3 (95% CI: 1.9, 27.6). Median follow-up for the cohort was 52 months; estimated median OS was 225 months with 5-year OS of 90%. Multivariate analysis identified older age at diagnosis and poor/moderate differentiation as factors that negatively impacted OS. 52 (35%) patients developed recurrent disease; the majority recurred with distant metastases (N=46, 88%), with liver being the most common site. Of those who recurred, 25 (48%) had received adjuvant therapy following resection. Estimated median disease free survival (DFS) was 74 months. Only poor/moderate differentiation affected DFS. Tumor size and LN+ did not significantly impact survival.
Results: PNET is an uncommon entity with an unclear prognosis based on variables commonly factored into the staging criteria. In this study, tumor size did not predict LN+; furthermore, LN+ did not predict a worse OS or DFS. Tumor differentiation appears to be more important in determining prognosis for resected PNET.