Lymph Node Ratio in Pancreatic Adenocarcinoma After Preoperative Chemotherapy vs. Preoperative Chemoradiation and Its Utility in Decisions About Postoperative Chemotherapy

J Gastrointest Surg. 2019 Jul;23(7):1401-1413. doi: 10.1007/s11605-018-3953-0. Epub 2018 Sep 5.

Abstract

Background: Single-center studies in pancreatic adenocarcinoma have suggested that preoperative chemotherapy (PCT) is associated with higher lymph node ratio (LNR) than preoperative chemoradiation (PCRT). The association of postoperative chemotherapy with overall survival (OS) in patients treated with PCT and PCRT remains unclear. Our objectives were to investigate whether (1) PCT is associated with higher LNR than PCRT and (2) postoperative chemotherapy is associated with longer OS after PCT and PCRT in LNR-stratified cohorts.

Methods: A retrospective cohort study was performed of patients with pancreatic adenocarcinoma treated with PCT or PCRT followed by resection between 2006 and 2014 in the National Cancer Database. Temporal trends were evaluated with Cuzick's test. OS was evaluated with multivariable Cox regression and inverse probability weighted (IPW) Cox regression.

Results: Of 4187 patients, 1993 (47.6%) received PCT. PCT rates were stable at approximately 30% in 2006-2010 (p = 0.33) but increased to 64.9% by 2014 (p < 0.001). Node positivity rates were higher after PCT than PCRT (62.7 vs. 41.8%, P < 0.001) and mean LNR was higher (0.10 [95% CI 0.096, 0.11] vs. 0.058 [95% CI 0.052, 0.063], P < 0.001). Postoperative chemotherapy was associated with longer OS in patients with LNR 0.01-0.149 after PCT by univariate analysis (median OS 34.5 vs. 26.5 months, P = 0.002), multivariable Cox regression (HR 0.64, 95% CI 0.48, 0.84), and IPW Cox regression (HR 0.72, 95% CI 0.55, 0.94). Postoperative chemotherapy was not associated with longer OS for patients who were node-negative or who had LNR ≥ 0.15 after PCT or for any patient subgroups after PCRT.

Conclusions: PCT is associated with a higher LNR and higher rates of node positivity than PCRT. Postoperative chemotherapy is associated with longer OS than observation in patients with a LNR of 0.01-0.149 after PCT.

Keywords: Adjuvant; Chemoradiation; Chemotherapy; LNR; Lymph node ratio; Neoadjuvant; Nodal status; PDAC; Pancreatic adenocarcinoma; Postoperative; Preoperative.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Pancreatic Ductal / mortality
  • Carcinoma, Pancreatic Ductal / pathology*
  • Carcinoma, Pancreatic Ductal / surgery*
  • Carcinoma, Pancreatic Ductal / therapy
  • Chemoradiotherapy
  • Chemotherapy, Adjuvant
  • Clinical Decision-Making
  • Female
  • Humans
  • Lymph Node Ratio*
  • Lymph Nodes / pathology
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology*
  • Pancreatic Neoplasms / surgery*
  • Pancreatic Neoplasms / therapy
  • Retrospective Studies
  • Survival Analysis
  • Young Adult