Patterns of recurrence after resection for pancreatic neuroendocrine tumors: who, when, and where?

Background/Aims Pancreatic Neuroendocrine Tumors (pan-NENs) represent an increasingly common indication for pancreatic resection, but there are few data regarding possible recurrence after surgery. Aim of the study is describing the frequency, timing, and patterns of recurrence after resection for pan-NENs with consequent implications for postoperative follow-up. Methods Retrospective analysis of pan-NEN resected between 1990 and 2015 at The Pancreas Institute, University of Verona Hospital Trust. Predictors of recurrence were assessed. Survival analysis was conducted using Kaplan-Maier and conditional survival (CS) methods. Results The cohort consisted of 487 patients with a median follow-up of 71 months. Recurrence developed in 12.3%: 54 (11.1%) liver metastases, 11 (2.3%) local recurrence, 10 (2.1%) nodal recurrence, and 8 (1.6%) metastases in other organs. Thirty-one (6.4%) died due to disease recurrence. Size >21 mm, G3 grade, nodal metastasis, and vascular infiltration were independent predictors of overall recurrence. Recurrence occurred either during the first year of follow-up (n= 9), or after ten years (n= 4). CS analysis revealed that non-functioning G1 pan-NEN ≤20mm without nodal metastasis or vascular invasion, had a negligible risk of developing recurrence. In the present series, after 5 years of follow-up without developing recurrence, tumor recurrence occurred only in the form of liver metastases. Conclusions Recurrence of pan-NENs is rare and is predicted by tumor size, nodal metastasis, grading, and vascular invasion. Patients with G1 pan-NEN without nodal metastasis and vascular invasion may be considered cured by surgery. After 5 years without recurrence, follow-up should focus on excluding the development of liver metastases.