Perineural Invasion Worsens Long-Term Outcomes of Pancreatic Neuroendocrine Tumors Following Surgical Resection

TL;DR

Perineural invasion in pancreatic neuroendocrine tumors is linked to worse long-term survival after surgery, even in early-stage cases.

Contribution

This study identifies perineural invasion as an independent prognostic factor for pancreatic neuroendocrine tumors after resection.

Findings

Perineural invasion was associated with higher tumor grade, more advanced T stage, and more nodal metastasis.

Patients with perineural invasion had significantly worse overall and disease-free survival.

Perineural invasion remained a strong independent risk factor even in early-stage, completely resected tumors.

Abstract

To define the impact of perineural invasion (PNI) on long-term survival of patients following curative-intent resection of pancreatic neuroendocrine tumors (pNETs).

Patients with pNETs who underwent curative-intent resection (R0/R1) between 2000 and 2020 were identified from a multi-institutional database. The impacts of PNI on overall survival (OS) and disease-free survival (DFS) were analyzed.

Among 700 patients, 171 (n = 24.4%) had a pNET with PNI. The presence of PNI was associated with higher tumor grade (G3, 8.2% vs. 2.5%, p < 0.001), more advanced AJCC T disease (T3–T4, 58.5% vs. 15.9%, p < 0.001), and a higher incidence of nodal metastasis (52.6% vs. 21.2%, p < 0.001) versus patients with no PNI. Patients with PNI had a worse OS (median, with PNI 115.9 months vs. no PNI not reached, p < 0.001) and DFS (median, with PNI 51.9 vs. no PNI 115.4 months, p < 0.001) versus patients with no PNI. On multivariable analysis PNI was an independent risk factor associated with worse OS (HR = 2.624, 95%CI 1.475–4.668, p = 0.001), as well as DFS (HR = 1.972, 95%CI 1.396–2.786, p < 0.001). Among 256 patients with very early staged tumors (G1N0) who underwent an R0 resection, PNI remained a strong independent factor associated with worse long-term survivals (OS, HR = 3.892, 95%CI 1.196–12.662, p = 0.024; DFS, HR = 2.530, 95%CI 1.010–6.339, p = 0.048).

PNI was an independent adverse prognostic factor among patients undergoing curative-intent resection of pNETs, even among individuals with early-stage disease. The presence of PNI should be routinely assessed and considered in the prognostic stratification of patients following resection of pNETs.

The online version contains supplementary material available at 10.1245/s10434-025-18561-6.

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