title: Feasibility of a randomized trial of extended lymphadenectomy for pancreatic cancer.
abstract: OBJECTIVE
  The required sample size of a prospective randomized trial comparing standard pancreaticoduodenectomy with pancreaticoduodenectomy plus extended lymphadenectomy for pancreatic adenocarcinoma is prohibitively large, making such a trial infeasible.
  
  
  METHODS
  Retrospective cohort study.
  
  
  METHODS
  Comprehensive cancer center.
  
  
  METHODS
  We identified 158 patients who underwent pancreaticoduodenectomy for pancreatic adenocarcinoma with separate pathologic analysis of second-echelon lymph nodes, defined as lymph nodes along the proximal hepatic artery and/or the great vessels.
  
  
  METHODS
  To estimate the sample size required for a randomized trial, we devised a biostatistical model with the following assumptions: extended lymphadenectomy can benefit only patients who (1) actually have disease removed from second-echelon nodes, (2) have microscopically negative (R0) primary tumor resection margins, and (3) do not have visceral metastatic (M0) disease.
  
  
  RESULTS
  Seventy-six patients (48.1%) had negative first- and second-echelon lymph nodes, 65 (41.1%) had positive first-echelon and negative second-echelon lymph nodes, and 17 (10.8%) had positive first- and second-echelon lymph nodes. Patients with positive second-echelon lymph nodes had an R0 resection rate of 47.1%. At a median follow-up of 65.1 months, 4 patients with positive second-echelon lymph nodes were alive, but 3 had recurrent disease. This implies that only 1 patient (5.9%) with positive second-echelon lymph nodes may have had true M0 disease. Therefore, only 0.3% of patients (10.8% with positive second-echelon lymph nodes x 47.1% with R0 resection x 5.9% with M0 disease) may achieve a survival benefit from extended lymphadenectomy. A randomized trial of standard pancreaticoduodenectomy vs pancreaticoduodenectomy with extended lymphadenectomy would require 202 000 patients in each study arm to detect such a small difference.
  
  
  CONCLUSIONS
  Definitive evaluation of the potential benefits of extended lymphadenectomy would require a prohibitively large sample size. Adequately powered randomized trials to address the potential benefit of extended lymphadenectomy are infeasible.
authors.affiliation: Department of Surgical Oncology and Pathology, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Pawlik
authors.forename: Eddie K
authors.initials: EK
authors.lastname: Abdalla
authors.forename: Carlton C
authors.initials: CC
authors.lastname: Barnett
authors.forename: Syed A
authors.initials: SA
authors.lastname: Ahmad
authors.forename: Karen R
authors.initials: KR
authors.lastname: Cleary
authors.forename: Jean-Nicolas
authors.initials: JN
authors.lastname: Vauthey
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Lee
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Evans
authors.forename: Peter W T
authors.initials: PW
authors.lastname: Pisters
mesh_terms: D000230:Adenocarcinoma / Q000601:surgery*; D004386:Duodenum / Q000601:surgery; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008197:Lymph Node Excision; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000601:surgery*; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D018401:Sample Size