Defining borderline resectability in pancreatic neuroendocrine tumors and the role of neoadjuvant therapy

BACKGROUND: Although surgical resection offers the best outcomes for patients with localized/oligometastatic pancreatic neuroendocrine tumors (pNET), definitions for borderline resectable (BR) disease to guide patient selection and neoadjuvant therapy (NT) have not been established. This study sought to validate a proposed definition of BR-pNET and evaluate the impact of NT and surgical resection on overall survival (OS). METHODS: Using the National Cancer Database, patients with invasive, well-differentiated pNETs were classified as BR [T4 stage and/or liver-only metastases] or resectable (<T4, without distant metastases). Kaplan-Meier and multivariable Cox regression models were used to evaluate OS. RESULTS: Among 15,473 patients, BR-pNET [2,945 (19%)], was independently associated with worse OS (HR 3.24, 95% CI 2.95-3.55; p<0.001). Among BR-pNET patients, resection was associated with longer median OS (128.6 vs 46.4 months; p<0.001). This benefit persisted in a 6-month landmark analysis (HR 0.36, 95% CI 0.30-0.44). NT use was uncommon (1.8%) and was not independently associated with survival (HR 1.14, 95% CI 0.66-1.97; p = 0.625). CONCLUSION: Among patients with well-differentiated pNET, borderline resectability was associated with worse OS, although surgical resection conferred meaningful survival benefit. The use of NT was uncommon and not associated with improved OS in this retrospective cohort.