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

Q: What is the study’s main aim regarding perineural invasion (PNI)?

To define how perineural invasion affects long-term overall survival and disease-free survival after curative-intent resection of pancreatic neuroendocrine tumors (pNETs).

Q: What did the results show about outcomes when PNI was present?

PNI was associated with worse overall survival and worse disease-free survival, and remained an independent adverse prognostic factor on multivariable analysis.

Sep 29, 2026

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Background. Define the impact of perineural invasion (PNI) on long-term survival after curative-intent resection of pancreatic neuroendocrine tumors (pNETs). Patients and Methods. Patients with pNETs undergoing curative-intent resection (R0/R1) from 2000 to 2020 were identified from a multi-institutional database; overall survival (OS) and disease-free survival (DFS) were analyzed. Results. In 700 patients, 171 (24.4%) had PNI, associated with higher tumor grade, more advanced AJCC T stage, and increased nodal metastasis, and worse OS and DFS, with PNI as an independent risk factor. Conclusions. PNI predicts adverse prognosis, including early-stage disease, and should be assessed for risk stratification.

LanguageEnglish

CategoryHealthcare

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Pages9

Reading Time23 min

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Abstract

Background

Patients and Methods

Results

Conclusions

Patients and Methods

Patient Cohort

Ann Surg Oncol (2026) 33:1586–1594 [https://doi.org/10.1245/s10434-025-18561-6](https://doi.org/10.1245/s10434-025-18561-6) ORIGINAL ARTICLE – PANCREATIC TUMORS Perineural Invasion Worsens Long‑Term Outcomes of Pancreatic Neuroendocrine Tumors Following Surgical Resection Hui Xu, MD1, Jing‑Jing Hou, MD1, Jun‑Xi Xiang, MD1, Alexandra G. Lopez‑Aguiar, MD2, George Poultsides, MD3, Flavio Rocha, MD4, Sharon Weber, MD5, Ryan Fields, MD6, Kamran Idrees, MD7, Cliff Cho, MD8, Shishir K. Maithel, MD3, Yi Lv, MD, PhD1, Xu‑Feng Zhang, MD, PhD1,9, and Timothy M. Pawlik, MD, PhD, MPH, MTS, MBA, FACS, FSSO, FRACS (Hon.)9 1Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China; 2Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia; 3Department of Surgery, Stanford University, Palo Alto, CA; 4Department of Surgery, Virginia Mason Medical Center, Seattle, WA; 5Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, WI; 6Department of Surgery, Washington University School of Medicine, St. Louis, WI; 7Division of Surgical Oncology, Department of Surgery, Vanderbilt University, Nashville, TN; 8Division of Hepatopancreatobiliary and Advanced Gastrointestinal Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI; 9Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH ABSTRACT 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 Hui Xu, Jing-Jing Hou and Jun-Xi Xiang have contribute equally to the study. © The Author(s) 2025 First Received: 27 June 2025 Accepted: 27 September 2025 Published online: 16 October 2025 X.-F. Zhang, MD, PhD e-mail: [xfzhang125@xjtu.edu.cn](xfzhang125@xjtu.edu.cn) T. M. Pawlik, MD, PhD, MPH, MTS, MBA, FACS, FSSO, FRACS (Hon.) e-mail: [tim.pawlik@osumc.edu](tim.pawlik@osumc.edu) 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), anda 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. Pancreatic neuroendocrine tumors (pNETs), originating from pancreatic islet cells of Langerhans, represent a rare malignancy accounting for 2–10% of all pancreatic neoplasms. 1 Although pNETs typically exhibit indolent behavior with slow progression, a distinct s

FAQs

What is the study’s main aim regarding perineural invasion (PNI)?

To define how perineural invasion affects long-term overall survival and disease-free survival after curative-intent resection of pancreatic neuroendocrine tumors (pNETs).

How were patients selected for analysis?

Patients with pNETs who underwent curative-intent resection (R0/R1) between 2000 and 2020 were identified from a multi-institutional database, and outcomes were analyzed for OS and DFS.

What did the results show about outcomes when PNI was present?

PNI was associated with worse overall survival and worse disease-free survival, and remained an independent adverse prognostic factor on multivariable analysis.

Sep 29, 2026

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