Patients with surgically resected pancreatic neuroendocrine tumors classified as G1 had a 10-year overall survival rate of 81%, compared with 23% for those with G3 tumors based on Ki-67 index, according to a recent study published in Endocrine Pathology.
In a single-institution retrospective study of 904 patients with surgically resected well-differentiated pancreatic neuroendocrine tumors (PanNETs), researchers at the Johns Hopkins University School of Medicine assessed long-term prognostic features by examining clinical, pathologic, and survival data over 7,882 person-years of follow-up. Tumors were graded using the Ki-67 proliferation index and stratified into four categories: G1 (<3%), G2a (3–<10%), G2b (10–≤20%), and G3 (>20%). Ten-year overall survival (OS) was 81% for G1, 68% for G2a, 44% for G2b, and 23% for G3 tumors. The stratification of G2 tumors into G2a and G2b was associated with differences in OS and recurrence risk.
Several histopathologic features were associated with worse OS, including vascular invasion (hazard ratio [HR], 3.00), tumor size of 2 cm or more (HR, 2.88), perineural invasion (HR, 2.42), and positive surgical margins (HR, 2.18) (all p<0.0001). Features associated with improved OS included insulinoma (HR, 0.34), the sclerosing variant (HR, 0.47), and the cystic variant (HR, 0.61). These associations remained consistent in subgroup analyses of patients with non-metastatic and node-negative disease. Among 251 patients with tumors less than 2 cm and T1N0M0 stage, the 10-year OS was 88%, and the 20-year disease-specific survival was 96%.
Multivariable analysis using the LASSO method identified Ki-67 index, age, tumor size, T, N, and M stage, and perineural invasion as independent prognostic variables. For patients with M0 disease, cumulative incidence of relapse at 5 years was 8% for G1, 25% for G2a, 62% for G2b, and 69% for G3 tumors. Relapse risk was also associated with tumor size, vascular invasion, and perineural invasion. Positive margins and invasive features remained prognostic in patients with T1N0M0 tumors.
A stage shift was observed over the study period, with an increased proportion of patients diagnosed at stage I, while mean age at diagnosis increased slightly. The study used two methods for assessing Ki-67, which were found to be strongly correlated. Overall, findings support the use of Ki-67–based grading and histopathologic characteristics in risk stratification of patients with surgically resected PanNETs.
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