Defining the Minimal and Optimal Thresholds for Lymph Node Resection and Examination for Intraductal Papillary Mucinous Neoplasm Derived Pancreatic Cancer: A Multicenter Retrospective Analysis

Abstract

OBJECTIVE: To establish minimal and optimal lymphadenectomy thresholds for intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic ductal adenocarcinoma (PDAC) and evaluate their prognostic value. BACKGROUND: Current guidelines recommend a minimum of 12 to 15 lymph nodes (LNs) in PDAC. This is largely based on pancreatic intraepithelial neoplasia (PanIN)-derived PDAC, a biologically distinct entity from IPMN-derived PDAC. METHODS: Multicenter retrospective study including consecutive patients undergoing upfront surgery for IPMN-derived PDAC was conducted. The minimum cutoff for lymphadenectomy was defined as the maximum number of LNs where a significant node positivity difference was observed. Maximally selected log-rank statistic was used to derive the optimal lymphadenectomy cutoff (maximize survival). Kaplan-Meier curves and log-rank tests were used to analyze overall survival (OS) and recurrence-free survival (RFS). Multivariable Cox regression was used to determine hazard ratios (HRs) with 95% confidence intervals (CI). RESULTS: In 341 patients with resected IPMN-derived PDAC, the minimum number of LNs needed to ensure accurate nodal staging was 10 ( P =0.040), whereas ≥20 LNs was the optimal number associated with improved OS (80.3 vs 37.2 months, P <0.001). Optimal lymphadenectomy was associated with improved OS [HR: 0.57 (95% CI: 0.39-0.83)] and RFS [HR: 0.70 (95% CI: 0.51-0.97)] on multivariable Cox regression. On subanalysis, the optimal lymphadenectomy cutoffs for pancreatoduodenectomy, distal pancreatectomy, and total pancreatectomy were 20 ( P <0.001), 23 ( P =0.160), and 25 ( P =0.008). CONCLUSIONS: In IPMN-derived PDAC, lymphadenectomy with at least 10 lymph nodes mitigates understaging, and at least 20 lymph nodes is associated with improved survival. Specifically, for pancreatoduodenectomy and total pancreatectomy, 20 and 25 lymph nodes were the optimal cutoffs.