Ki-67 and presence of liver metastases identify different progression-risk classes in pancreatic neuroendocrine neoplasms (pNEN) undergoing resection

In pancreatic neuroendocrine neoplasms (pNEN), size ≤2 cm and Ki-67 < 3% suggest indolent behavior, but no factor alone predicts prognosis. We investigated factors predictive of tumor progression in 80 pNENs surgically resected in a single Institution from 1995 to 2015. At multivariable analysis the only two independent variables related to PFS were Ki-67 (HR 2.97; 95%CI 1.26-7.02) and presence of synchronous liver metastases (HR 3.60; 95%CI 1.70-7.61). Using Ki-67 < 3% and M0 as reference, the HR for tumor progression was 3.21 (95%CI 1.18-8.74) for M0 patients with Ki-67 3-20%, 5.06 (2.29-11.2) for M1 patients with Ki-67 ≤ 20% and 24.3 (6.64-89.2) for those with Ki-67 > 20%. Tumor size (≤2 vs. >2 cm) was not a predictive factor at any analysis. Intra-class correlation of Ki-67 values on pre-surgical biopsies vs. surgical specimens was 0.99 and Ki-67 classes were correctly identified in 97% of biopsies. Ki-67 and presence of liver metastases are the major prognostic factors in pNEN and identify different progression risks regardless of tumor size. Pre-surgical pNEN biopsy for Ki-67 assessment should be included in the evaluation of patients with 1-2 cm tumors to help in the decision on whether to perform surgical resection.