Predictors of disease progression in pancreatic neuroendocrine tumors after surgery

Pancreatic neuroendocrine tumors (pNETs) are a heterogeneous group of tumors that exhibit a range of biological behaviors, from indolent to aggressive. Identifying prognostic factors for pNETs is essential for risk stratification and personalized treatment planning. Clinicopathological data of stage I to III patients who underwent pancreatic resection and were treated for pNET at an ENETS Center of Excellence from 2009 to 2023 were analyzed retrospectively. 89 pNET patients were included (45 female, 44 male). Proximal pNETs had higher proportions of lymph node metastases (48.4% vs. 17.2%, p = 0.002) and shorter progression-free survival (PFS) compared to distal tumors (5-year PFS 56.2% vs. 85.0%, p = 0.003). Subdivision of G2 into G2a (Ki67 3-<10%) and G2b (Ki67 10-20%) identified shorter PFS in G2b than in G1 and G2a tumors (5-year PFS G1: 93.6%, G2a: 73.5%, G2b: 34.3%, p < 0.001) while PFS did not differ between G2b and G3 (34.3% vs. 28.6%, p = 0.192). Cox regression analyses revealed tumor grading (G2b: HR 8.396 (2.025-34.081), p = 0.003; G3: HR 17.649 (3.912-79.627), p < 0.001) and lymph node metastases (HR 2.657 (1.040-6.789), p = 0.041) as risk factors for shorter PFS.Tumor grading and lymph node metastases are independent predictors of postoperative disease progression in pNET patients without distant metastases. Subdividing G2 tumors into G2a and G2b improves prognostic discrimination, with G2b tumors demonstrating outcomes comparable to G3 tumors. These findings support the incorporation of refined grading into treatment and follow-up considerations.