When Should Lymphadenectomy Be Performed in Non-Metastatic Pancreatic Neuroendocrine Tumors? A Population-Based Analysis of the German Clinical Cancer Registry Group

Background: Patient selection for lymphadenectomy remains a controversial aspect in the treatment of pancreatic neuroendocrine tumors (pNETs), given the growing importance of parenchyma-sparing resections and minimally invasive procedures. Methods: This population-based analysis was derived from the German Cancer Registry Group during the period from 2000 to 2021. Patients with upfront resected non-functional non-metastatic pNETs were included. Results: Out of 5520 patients with pNET, 1006 patients met the inclusion criteria. Fifty-three percent of the patients were male. The median age was 64 ± 17 years. G1, G2, and G3 pNETs were found in 57%, 37%, and 7% of the patients, respectively. Lymph node metastasis (LNM) was present in 253 (24%) of all patients. LNM was an independent prognostic factor (HR 1.79, CI 95% 1.21–2.64, p = 0.001) for disease-free survival (DFS). The 3-, 5-, and 10-year disease-free survival in nodal negative tumors compared to nodal positive was 82% vs. 53%, 75% vs. 38%, and 48% vs. 16%. LNM was present in 5% of T1 tumors, 25% of T2 tumors, and 49% of T3–T4 tumors. In T1 tumors, G1 was the most predominant tumor grade (80%). However, in T2 tumors, G2 and G3 represented 44% and 5% of all tumors. LNM was associated with tumors located in the pancreatic head (p < 0.001), positive resection margin (p < 0.001), tumors larger than 2 cm (p < 0.001), and higher tumor grade (p < 0.001). The multivariable analysis showed that tumor size, tumor grade, and location were independent prognostic factors associated with LNM that could potentially be used to predict LNM preoperatively. Conclusion: LNM is an independent negative prognostic factor for DFS in pNETs. Due to the low incidence of LNM in T1 tumors (5%), parenchyma-sparing surgery seems oncologically adequate in small G1 pNETs, while regional lymphadenectomy should be recommended in T2 or G2/G3 pNETs.