Determining which patients should undergo lymphadenectomy remains a debated issue in the management of pancreatic neuroendocrine tumors (pNETs), particularly with the increasing adoption of parenchyma-sparing and minimally invasive surgical techniques. This study utilized data from the German Cancer Registry Group, encompassing cases between 2000 and 2021. Only patients who underwent upfront resection for non-functional, non-metastatic pNETs were included. Among 5520 recorded pNET cases, 1006 fulfilled the inclusion criteria. Males represented 53% of the cohort, and the median patient age was 64 ± 17 years. Tumor grading revealed that 57% were G1, 37% G2, and 7% G3. Lymph node metastasis (LNM) occurred in 253 patients (24%) and emerged as an independent predictor of poorer disease-free survival (DFS) (HR 1.79, 95% CI 1.21–2.64, p = 0.001). DFS at 3, 5, and 10 years was notably higher in lymph node-negative patients compared with those positive for nodal involvement (82% vs. 53%, 75% vs. 38%, and 48% vs. 16%, respectively). The incidence of LNM increased with tumor stage—5% in T1, 25% in T2, and 49% in T3–T4 tumors. G1 predominated in T1 tumors (80%), whereas G2 and G3 accounted for 44% and 5% of T2 lesions. LNM was significantly associated with tumor location in the pancreatic head (p < 0.001), positive surgical margins (p < 0.001), tumor size exceeding 2 cm (p < 0.001), and higher histologic grade (p < 0.001). Multivariate analysis identified tumor size, grade, and anatomical location as independent risk factors for LNM, suggesting their potential use in preoperative prediction. LNM serves as a strong, independent negative prognostic marker for DFS in pNETs. Given the minimal LNM occurrence in small T1, G1 tumors (5%), limited parenchyma-preserving resections appear oncologically sufficient in such cases. Conversely, regional lymphadenectomy is advisable for patients with T2 or G2/G3 pNETs.
