title: Preoperative chemotherapy is effective for stage III resectable non--small-cell lung cancer: metaanalysis of 16 trials.
abstract: BACKGROUND
  The benefit of preoperative chemotherapy for resectable non-small-cell lung cancer is still controversial.
  
  
  METHODS
  We conducted fixed-model metaanalysis including randomized controlled trials comparing 'preoperative chemotherapy plus surgery' and 'surgery alone' as a primary study with sufficient data to provide a hazard ratio for overall survival. MEDLINE and Cochrane databases were used for the study search.
  
  
  RESULTS
  We found 16 studies. Seven included only stage III disease cases, and 9 were conducted without stage limitation. Sixteen trials involving 3728 samples observing 2326 deaths yielded a pooled hazard ratio for overall survival of 0.84 (95% confidence interval [CI], 0.77-0.91; P < .001) with moderate heterogeneity (I(2) = 40%). In sensitivity analysis, strong heterogeneity (I(2) = 69%) was found between the 7 trials covering only stage III disease and 9 trials without stage limitation. The 7 studies evaluating only stage III disease involving 1447 samples and 1068 deaths yielded a pooled hazard ratio of 0.77 (95% CI, 0.68-0.87; P < .001) with nonsignificant low heterogeneity (I(2) = 17%). No publication bias was observed throughout this study. The effect of preoperative chemotherapy differs among stages. The pooled hazard ratio comparing 'preoperative chemotherapy plus surgery' and 'surgery alone' for patients with stage III disease in our study was 0.77, which is slightly better than the pooled hazard ratio of 0.83 in the Lung Adjuvant Cisplatin Evaluation study that compared 'surgery plus postoperative chemotherapy' and 'surgery alone.'
  
  
  CONCLUSIONS
  Preoperative chemotherapy plus surgery for stage III disease is more effective than previously considered.
authors.affiliation: Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, Yokohama, Japan. nobuyuki_horita@yahoo.co.jp
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Horita
authors.forename: Naoki
authors.initials: N
authors.lastname: Miyazawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morita
authors.forename: Ryota
authors.initials: R
authors.lastname: Kojima
authors.forename: Naoko
authors.initials: N
authors.lastname: Kimura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kaneko
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ishigatsubo
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D009367:Neoplasm Staging; D011300:Preoperative Care; D011379:Prognosis
keywords: Neoadjuvant chemotherapy; Overall survival; Randomized controlled trial; Surgery; Systematic review