Surgical and Oncologic Outcomes After Pancreatectomy for Pancreatic Neuroendocrine Tumor in Multiple Endocrine Neoplasia Type 1 and von Hippel-Lindau Syndrome: A Large, Multi-Institutional, Cohort Study

Background: Pancreatic neuroendocrine tumors (PNETs) are associated with multiple endocrine neoplasia type 1 (MEN1) and von Hippel-Lindau syndrome (VHL) yet data regarding surgical outcomes in these patients is lacking. This study compared outcomes after pancreatectomy across a large cohort of sporadic, MEN1-, and VHL-PNET patients. Study Design: Retrospective analysis of pancreatectomies for PNETs performed at five institutions in the United States between 2000-2023 as part of the PAncreatic Neuroendocrine Disease Alliance (PANDA). All adult patients with MEN1- and VHL-associated PNETs were included. Adult sporadic PNET patients with overall survival and tumor grade data were included. Results Of 1,527 patients, 73 had MEN1, 26 had VHL, and 1,428 had sporadic PNETs. Majority were male (54%) with median age of 59 years (IQR 50-68). Median follow-up was 53 months. MEN1 and VHL patients were significantly younger and had more pancreatic head and multifocal disease compared to sporadic patients. MEN1 patients had more functional tumors (19.2% vs 10.9% sporadic vs 3.8% VHL, p=0.045). Formal resection was most common while enucleation occurred in 9.4%, 6.8%, and 3.8% of sporadic, MEN1-, and VHL-PNETs respectively. Tumors were predominantly Grade 1/2 (97%) but larger in MEN1 (2.8cm vs 2.3cm sporadic vs 2.5cm VHL, p=0.03). R2 resection occurred in 2.6% of sporadic, 9.6% of MEN1-, and 3.8% of VHL-PNETs. Rates of lymphadenectomy (86-92%), positive lymph nodes (24-31%), and Clavien-Dindo grade ≥3 complications were similar across groups. Progression-free survival (PFS) and overall survival (OS) among groups were not significantly different. Conclusion Despite significant differences in age, tumor size, R status, and surgical approach, outcomes including postoperative complications, PFS and OS after surgery are similar between sporadic, MEN1-, and VHL-associated PNET patients at 5-year follow-up.