Fate of Surgical Patients with Small Nonfunctioning Pancreatic Neuroendocrine Tumors: An International Study Using Multi-Institutional Registries

SIMPLE SUMMARY: No consensus has been reached regarding whether nonmetastatic nonfunctioning neuroendocrine tumors of the pancreas (NF-pNETs) ≤ 2 cm should be resected or observed. In this retrospective international multicenter study, 483 patients who underwent resection for NF-pNETs ≤ 2 cm in 18 institutions from 2000 to 2017 were enrolled and their medical records were reviewed. Tumor size > 1.5 cm, Ki-67 index ≥ 3%, and nodal metastasis were independent adverse prognostic factors for survival after multivariable analysis. NF-pNET patients with tumors ≤ 1.5 cm can be observed if the preoperative Ki-67 index is under 3%, and if nodal metastasis is not suspected in preoperative radiologic studies. These findings support the clinical use to make decisions about small NF-pNETs. ABSTRACT: Several treatment guidelines for sporadic, nonmetastatic nonfunctioning neuroendocrine tumors of the pancreas (NF-pNETs) have recommended resection, however, tumors ≤ 2 cm do not necessarily need surgery. This study aims to establish a surgical treatment plan for NF-pNETs ≤ 2 cm. From 2000 to 2017, 483 patients who underwent resection for NF-pNETs ≤ 2 cm in 18 institutions from Korea and China were enrolled and their medical records were reviewed. The median age was 56 (range 16–80) years. The 10-year overall survival rate (10Y-OS) and recurrence-free survival rate (10Y-RFS) were 89.8 and 93.1%, respectively. In multivariable analysis, tumor size (>1.5 cm; HR 4.28, 95% CI 1.80–10.18, p = 0.001) and nodal metastasis (HR 3.32, 95% CI 1.29–8.50, p = 0.013) were independent adverse prognostic factors for OS. Perineural invasion (HR 4.36, 95% CI 1.48–12.87, p = 0.008) and high Ki-67 index (≥3%; HR 9.06, 95% CI 3.01–27.30, p < 0.001) were independent prognostic factors for poor RFS. NF-pNETs ≤ 2 cm showed unfavorable prognosis after resection when the tumor was larger than 1.5 cm, Ki-67 index ≥ 3%, or nodal metastasis was present. NF-pNET patients with tumors ≤ 1.5 cm can be observed if the preoperative Ki-67 index is under 3%, and if nodal metastasis is not suspected in preoperative radiologic studies. These findings support the clinical use to make decisions about small NF-pNETs.