Defining the role of lymphadenectomy for pancreatic neuroendocrine tumors: An eight institution study of 695 patients from the U.S. Neuroendocrine Tumor Study Group.

Abstract

212 Background: Preoperative factors that reliably predict lymph node (LN) metastases in pancreatic neuroendocrine tumors (PanNETs) are unclear. The number of LNs needed to accurately stage PanNETs has not been defined. Methods: Patients who underwent curative-intent resection of primary non-functional PanNETs at 8 institutions from 2000-2016 were analyzed. Tumors with poor differentiation and Ki-67 > 20% were excluded. Preoperative factors associated with LN metastases were identified. A procedure specific target for LN retrieval to accurately stage patients was determined. Results: Of 2182 pts with GI NETs, 695 underwent resection of PanNETs. 33% of tumors were proximal (head/uncinate), and 67% were distal (neck/body/tail). 26% of pts (n = 158) had LN+ disease, which was associated with worse 5-yr recurrence-free survival (RFS) (60% vs 86%; p < 0.001). Increasing number of +LNs was not associated with worse RFS. Preoperative factors associated with +LNs included tumor size ≥2 cm (OR 6.6; p < 0.001), proximal location (OR 2.5; p < 0.001), moderate vs well differentiation (OR 2.1; p = 0.006), and Ki-67≥3% (OR 3.1; p < 0.001). LN metastases were also present in tumors without these risk factors: < 2cm (9%), distal location (19%), well differentiated (23%), and Ki-67 < 3% (16%). Median LN retrieval was 13 for pancreatoduodenectomy (PD), but only 9 for distal pancreatectomy (DP). Given that PD routinely includes a complete regional lymphadenectomy, a minimum number of LNs to accurately stage pts was not identified. For DP, however, removal of < 7 LNs failed to discriminate 5-yr RFS between LN (+) and (-) pts ( < 7 LNs: 72% vs 83%, p = 0.198; ≥7 LNs: 67% vs 86%, p = 0.002). Conclusions: Tumor size ≥2 cm, proximal location, moderate differentiation, and Ki-67≥3% are preoperative factors that predict LN positivity in resected non-functional PanNETs. Given the 9-23% incidence of LN metastases in patients without such risk factors, routine regional lymphadenectomy should be considered. Pancreatoduodenectomy inherently includes sufficient LN retrieval, while distal pancreatectomy should aim to remove ≥7 LNs for accurate staging.