International assessment and validation of the prognostic role of lymph node ratio in patients with resected pancreatic head ductal adenocarcinoma

Gaëtan-Romain Joliat; Ismail Labgaa; Jesse Sulzer; Dionisios Vrochides; Alessandro Zerbi; Gennaro Nappo; Julie Perinel; Mustapha Adham; Stijn van Roessel; Marc G Besselink; J Sven D Mieog; Jesse V Groen; Nicolas Demartines; Markus Schäfer

doi:10.21037/hbsn-21-99

International assessment and validation of the prognostic role of lymph node ratio in patients with resected pancreatic head ductal adenocarcinoma

Hepatobiliary Surg Nutr. 2022 Dec;11(6):822-833. doi: 10.21037/hbsn-21-99.

Authors

Affiliations

¹ Department of Visceral Surgery, Lausanne University Hospital CHUV, Lausanne, Switzerland.
² Graduate School for Health Sciences, University of Bern, Bern, Switzerland.
³ Division of Hepatobiliary and Pancreatic Surgery, Carolinas Medical Center, Charlotte, NC, USA.
⁴ Humanitas Clinical and Research Center-IRCCS, Milan, Italy.
⁵ Department of Biomedical Sciences, Humanitas University, Milan, Italy.
⁶ Department of Digestive Surgery, Edouard Herriot Hospital, Lyon, France.
⁷ Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
⁸ Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.

Abstract

Background: Lymph node ratio (LNR; positive/harvested lymph nodes) was identified as overall survival predictor in several cancers, including pancreatic adenocarcinoma. It remains unclear if LNR is predictive of overall survival in pancreatic adenocarcinoma patients staged pN2. This study assessed the prognostic overall survival role of LNR in pancreatic adenocarcinoma patients in relation with lymph node involvement.

Methods: A retrospective international study in six different centers (Europe and United States) was performed. Pancreatic adenocarcinoma patients who underwent pancreatoduodenectomy from 2000 to 2017 were included. Patients with neoadjuvant treatment, metastases, R2 resections, or missing data regarding nodal status were excluded. Survival curves were calculated using Kaplan-Meier method and compared using log-rank test. Multivariable Cox regressions were performed to find independent overall survival predictors adjusted for potential confounders.

Results: A total of 1,327 patients were included. Lymph node involvement (pN+) was found in 1,026 patients (77%), 561 pN1 (55%) and 465 pN2 (45%). Median LNR in pN+ patients was 0.214 [interquartile range (IQR): 0.105-0.364]. On multivariable analysis, LNR was the strongest overall survival predictor in the entire cohort [hazard ratio (HR) =5.5; 95% confidence interval (CI): 3.1-9.9; P<0.001] and pN+ patients (HR =3.8; 95% CI: 2.2-6.6; P<0.001). Median overall survival was better in patients with LNR <0.225 compared to patients with LNR ≥0.225 in the entire cohort and pN+ patients. Similar results were found in pN2 patients (worse overall survival when LNR ≥0.225).

Conclusions: LNR appeared as an important prognostic factor in patients undergoing surgery for pancreatic adenocarcinoma and permitted to stratify overall survival in pN2 patients. LNR should be routinely used in complement to tumor-node-metastasis (TNM) stage to better predict patient prognosis.

Keywords: Pancreatectomy; cancer; lymphatic involvement.