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

Background: To define the impact of perineural invasion (PNI) on long-term survival of patients following curative-intent resection of pancreatic neuroendocrine tumors (pNETs). Patients and Methods: 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. Results: 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). Conclusions: 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.