Patterns of Lymph Node Metastasis and Optimal Surgical Strategy in Small (≤20 mm) Gastroenteropancreatic Neuroendocrine Tumors

Abstract

Background: Regional lymph node metastasis (LNM) is crucial for planning additional lymphadenectomy, and is directly correlated with poor prognosis in gastroenteropancreatic neuroendocrine tumors (GEP-NETs). However, the patterns of LNM for small (≤20 mm) GEP-NETs remain unclear. This population-based study aimed at evaluating LNM patterns and identifying optimal surgical strategies from the standpoint of lymph node dissemination.

Methods: This retrospective cohort study retrieved data from the Surveillance, Epidemiology, and End Results (SEER) 18 registries database for 17,308 patients diagnosed as having localized well-differentiated GEP-NETs ≤ 20 mm between January 1, 2004, and December 31, 2017. The patterns of LNM were characterized in 6,622 patients who underwent extended resection for adequate lymph node harvest.

Results: Of 6,622 patients with localized small GEP-NETs in the current study, 2,380 (36%) presented with LNM after regional lymphadenectomy. Nodal involvement was observed in approximately 7.4%, 49.1%, 13.6%, 53.7%, 13.8%, 7.8%, and 15.4% of gastric (g-), small intestinal (si-), appendiceal (a-), colonic (c-), rectal (r-), non-functional pancreatic (nfp-), and functional pancreatic (fp-) NETs ≤ 20 mm. Patients with younger age, larger tumor size, and muscularis invasion were more likely to present with LNM. Additional lymphadenectomy conferred a significant survival advantage in NETs (≤10 mm: HR, 0.47; 95% CI, 0.33-0.66; p < 0.001; 11-20 mm: HR, 0.54; 95% CI, 0.34-0.85; p = 0.008) and fp-NETs ≤ 20 mm (HR, 0.08; 95% CI, 0.02-0.36; p = 0.001), as well as g-NETs (HR, 0.39; 95% CI, 0.16-0.96; p = 0.041) and c-NETs of 11-20 mm (HR, 0.07; 95% CI, 0.01-0.48; p = 0.007). Survival benefits of additional lymphadenectomy were not found in a-NETs, r-NETs, and nfp-NETs with a small size.

Conclusions: Given the increased risk for nodal metastasis, primary tumor resection with regional lymphadenectomy is a potential optimal surgical strategy for si-NETs and fp-NETs ≤ 20 mm, as well as g-NETs and c-NETs of 11-20 mm. Local resection is an appropriate and reliable surgical approach for a-NETs, r-NETs, and nfp-NETs ≤ 20 mm.

Keywords: SEER database; gastroenteropancreatic neuroendocrine tumors; lymph node metastatic patterns; small tumor size; surgical strategy.

Figure 1

Kaplan–Meier curves for cancer-specific and overall survival for all patients with small well-differentiated GEP-NETs stratified by LN status. (A) Kaplan–Meier analysis of cancer-specific survival. (B) Kaplan–Meier analysis of overall survival. GEP-NETs, gastroenteropancreatic neuroendocrine tumors; LN, lymph node.

Figure 2

Overall survival comparison of different surgical strategies stratified by tumor location and size among patients with small well-differentiated GEP-NETs. (A) The g-NETs of the ≤10 mm cohort; (B) the g-NETs of the 11–20 mm cohort; (C) the si-NETs of the ≤10 mm cohort; (D) the si-NETs of the 11–20 mm cohort; (E) the c-NETs of the 11–20 mm cohort; (F) the r-NETs of the 11–20 mm cohort; (G) the nfp-NETs of the ≤20 mm cohort; and (H) the fp-NETs of the ≤20 mm cohort. GEP-NETs, gastroenteropancreatic neuroendocrine tumors; LR, local resection; ER, extended resection; g-NETs, gastric neuroendocrine tumors; si-NETs, small intestinal neuroendocrine tumors; c-NETs, colonic neuroendocrine tumors; r-NETs, rectal neuroendocrine tumors; nfp-NETs, non-functional pancreatic neuroendocrine tumors; fp-NET, functional pancreatic neuroendocrine tumors.