The conundrum of < 2-cm pancreatic neuroendocrine tumors: A preoperative risk score to predict lymph node metastases and guide surgical management

Background: Management of <2-cm pancreatic neuroendocrine tumors is controversial. Although often indolent, the oncologic heterogeneity of these tumors particularly related to lymph node metastases poses challenges when deciding between resection versus surveillance. Methods: We analyzed all patients who underwent resection of primary nonfunctional <2-cm with curative-intent at 8 institutions of the US Neuroendocrine Tumor Study Group from 2000 to 2016. Pancreatic neuroendocrine tumors with poor differentiation and Ki-67 > 20% were excluded. Our primary aim was to create a lymph node risk score that predicted lymph node metastases accurately for <2-cm pancreatic neuroendocrine tumors, utilizing readily available preoperative data. Results: Of 695 patients with resected pancreatic neuroendocrine tumors, 309 were <2 cm. Of these small pancreatic neuroendocrine tumors, 25% were proximal (head/uncinate), 23% had a Ki-67 > 3%, and only 8% were moderately differentiated. Also, only 9% of all <2-cm pancreatic neuroendocrine tumors were lymph node (+). Indeed lymph node positivity was associated with worse 5-year recurrence-free survival compared with lymph node (–) disease (80% vs 96%; P = .007). Factors known preoperatively to be associated with lymph node metastases were proximal location (odds ratio 4.0; P = .002) and Ki-67 ≥3% (odds ratio 2.7; P = .05). Moderate differentiation was not associated with lymph node (+) disease. Location and Ki-67 were assigned a value weighted by their odds ratio: (distal= 1, proximal= 4, and Ki-67 < 3% = 1 and Ki-67 ≥ 3% = 3), which formed a lymph node risk score ranging 1–7. Scores were categorized into low (1–2), intermediate (3–4), and high (5–7) risk groups. Incidence of lymph node metastases increased progressively based on risk group, with low = 3.2%, intermediate = 13.8%, and high = 20.5%. Only 3.4% of pancreatic neuroendocrine tumors with a Ki-67 < 3% in the distal pancreas were lymph node (+) compared with 21.4% of pancreatic neuroendocrine tumors with a Ki-67 ≥ 3% in the head/uncinate. Conclusion: This simple and novel lymph node risk score utilizes readily available preoperative factors (tumor location and Ki-67) to stratify risk of lymph node metastases accurately s for < 2-cm pancreatic neuroendocrine tumors and may help guide management strategy.