title: A meta-analysis of randomized controlled trials that compared neoadjuvant chemotherapy and surgery to surgery alone for resectable esophageal cancer.
abstract: BACKGROUND
  Esophagectomy is often considered the standard treatment for resectable esophageal cancer but the rate of cure is low. Combining neoadjuvant chemotherapy with surgery has theoretical appeal and some clinical evidence suggests a benefit. We performed a meta-analysis of randomized controlled trials (RCTs) that compared neoadjuvant chemotherapy and surgery with surgery alone for esophageal cancer.
  
  
  METHODS
  Medline and manual searches were done to identify all published RCTs that compared neoadjuvant chemotherapy and surgery to surgery alone for esophageal cancer. The selection process was inclusive; no trials were excluded. Trial validity assessment was done and a trial quality score was assigned. Outcomes assessed by meta-analysis included 1-, 2-, and 3-year survival, rate of resection, rate of complete resection, operative mortality, anastomotic leaks, postoperative pulmonary complications, all treatment mortality, local-regional cancer recurrence, distant cancer recurrence, and all cancer recurrence. A random-effects model was used and odds ratio was the principal measure of effect. Systematic quantitative review was done for outcomes unique to the neoadjuvant chemotherapy treatment group (clinical response, pathological complete response, and chemotherapy mortality).
  
  
  RESULTS
  Eleven RCTs, which included 1,976 patients, were selected with quality scores ranging from 1 to 3 (5-point Jadad scale). Odds ratio (95% confidence interval [CI]; P value), expressed as chemotherapy and surgery versus surgery alone (treatment versus control; values <1 favor chemotherapy-surgery arm), was 1.00 (0.76, 1.30; P = 0.98) for 1-year survival, 0.88 (0.62, 1.24; P = 0.45) for 2-year survival, 0.77 (0.37, 1.59; P = 0.48) for 3-year survival, 1.71 (1.22, 2.40; P = 0.002) for rate of resection, 0.71 (0.58, 0.87; P = 0.001) for rate of complete resection, 0.94 (0.66, 1.35; P = 0.76) for operative mortality, 1.08 (0.45, 2.60; P = 0.87) for anastomotic leaks, 1.31 (0.77, 2.23; P = 0.32) for postoperative pulmonary complications, 1.36 (0.83, 2.25; P = 0.22) for all treatment mortality, 0.71 (0.36, 1.42; P = 0.33) for local-regional cancer recurrence, 0.79 (0.57, 1.10; P = 0.16) for distant cancer recurrence, and 0.63 (0.28, 1.41; P = 0.26) for all cancer recurrence. A clinical response to chemotherapy was observed in 31% of patients and 5% had a complete pathological response. Chemotherapy mortality (before surgery) was 1.6%.
  
  
  CONCLUSIONS
  Compared with surgery alone, neoadjuvant chemotherapy and surgery is associated with a lower rate of esophageal resection but a higher rate of complete (R0) resection. It does not increase treatment related mortality. This meta-analysis did not demonstrate a survival benefit for the combination of neoadjuvant chemotherapy and surgery.
authors.affiliation: Department of Surgery, McMaster University, Hamilton, Ontario, Canada. urschelj@mcmaster.ca
authors.forename: John D
authors.initials: JD
authors.lastname: Urschel
authors.forename: Hari
authors.initials: H
authors.lastname: Vasan
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Blewett
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D016629:Esophagectomy / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012016:Reference Values; D016019:Survival Analysis; D016896:Treatment Outcome