Margin status and long-term prognosis of primary pancreatic neuroendocrine tumor after curative resection: Results from the US Neuroendocrine Tumor Study Group

Background: The impact of margin status on resection of primary pancreatic neuroendocrine tumors has been poorly defined. The objectives of the present study were to determine the impact of margin status on long-term survival of patients with pancreatic neuroendocrine tumors after curative resection and evaluate the impact of reresection to obtain a microscopically negative margin. Methods: Patients who underwent curative-intent resection for pancreatic neuroendocrine tumors between 2000 and 2016 were identified at 8 hepatobiliary centers. Overall and recurrence-free survival were analyzed relative to surgical margin status using univariable and multivariable analyses. Results: Among 1,020 patients, 866 (84.9%) had an RO (>1 mm margin) resection, whereas 154 (15.1%) had an R1 (<= 1 mm margin) resection. R1 resection was associated with a worse recurrence-free survival(10-year recurrence-free survival, R1 47.3% vs RO 62.8%, hazard ratio 1.8, 95% confidence interval 1.2-2.7, P = .002); residual tumor at either the transection margin (R1t) or the mobilization margin (Rim) was associated with increased recurrence versus RO (R1t versus RO: hazard ratio 1.8, 95% confidence interval 1.0-3.0, P = .033; R1m versus RO: hazard ratio 1.3, 95% confidence interval 1.0 similar to 1.7, P = .060). In contrast, margin status was not associated with overall survival (10-year overall survival, R1 71.1% vs RO 71.8%, P = .392). Intraoperatively, 539 (53.6%) patients had frozen section evaluation of the surgical margin; 49 (9.1%) patients had a positive margin on frozen section analysis; 38 of the 49 patients (77.6%) had reresection, and a final RO (secondary RO) margin was achieved in 30 patients (78.9%). Extending resection to achieve an RO status remained associated with worse overall survival (hazard ratio 3.1, 95% confidence interval 1.6-6.2, P = .001) and recurrence-free survival (hazard ratio 2.6, 95% confidence interval 1.4-5.0, P = .004) compared with primary RO resection. On multivariable analyses, tumor-specific factors, such cellular differentiation, perineural invasion, Ki-67 index, and major vascular invasion, rather than surgical margin, were associated with long-term outcomes. Conclusion: Margin status was not associated with long-term survival. The reresection of an initially positive surgical margin to achieve a negative margin did not improve the outcome of patients with pancreatic neuroendocrine tumors. Parenchymal-sparing pancreatic procedures for pancreatic neuroendocrine tumors may be appropriate when feasible. (C) 2018 Elsevier Inc. All rights reserved.