title: Lymphovascular invasion as a prognostic indicator in stage I non-small cell lung cancer: a systematic review and meta-analysis.
abstract: BACKGROUND
  Lymphovascular invasion (LVI) is considered a high-risk pathologic feature in resected non-small cell carcinoma (NSCLC). The ability to stratify stage I patients into risk groups may permit refinement of adjuvant treatment recommendations. We performed a systematic review and meta-analysis to evaluate whether the presence of LVI is associated with disease outcome in stage I NSCLC patients.
  
  
  METHODS
  A systematic search of the literature was performed (1990 to December 2012 in MEDLINE/EMBASE). Two reviewers independently assessed the quality of the articles and extracted data. Pooled hazard ratios (HRs) and 95% confidence intervals (CI) were estimated with a random effects model. Two end points were independently analyzed: recurrence-free survival (RFS) and overall survival (OS). We analyzed unadjusted and adjusted effect estimates, resulting in four separate meta-analyses.
  
  
  RESULTS
  We identified 20 published studies that reported the comparative survival of stage I patients with and without LVI. The unadjusted pooled effect of LVI was significantly associated with worse RFS (HR, 3.63; 95% CI, 1.62 to 8.14) and OS (HR, 2.38; 95% CI, 1.72 to 3.30). Adjusting for potential confounders yielded similar results, with RFS (HR, 2.52; 95% CI, 1.73 to 3.65) and OS (HR, 1.81; 95% CI, 1.53 to 2.14) both significantly worse for patients exhibiting LVI.
  
  
  CONCLUSIONS
  The present study indicates that LVI is a strong prognostic indicator for poor outcome for patients with surgically managed stage I lung cancer. Future prospective lung cancer trials with well-defined methods for evaluating LVI are necessary to validate these results.
authors.affiliation: Department of Cardiothoracic Surgery, University of Washington, Seattle, Washington. Electronic address: nathan.mollberg@gmail.com.
authors.forename: Nathan M
authors.initials: NM
authors.lastname: Mollberg
authors.affiliation: Pharmaceutical Outcomes Research and Policy Program, University of Washington, Seattle, Washington.
authors.forename: Carrie
authors.initials: C
authors.lastname: Bennette
authors.affiliation: Department of Cardiothoracic Surgery, University of Washington, Seattle, Washington.
authors.forename: Eric
authors.initials: E
authors.lastname: Howell
authors.affiliation: Department of Cardiothoracic Surgery, University of Washington, Seattle, Washington.
authors.forename: Leah
authors.initials: L
authors.lastname: Backhus
authors.affiliation: Pharmaceutical Outcomes Research and Policy Program, University of Washington, Seattle, Washington.
authors.forename: Beth
authors.initials: B
authors.lastname: Devine
authors.affiliation: Department of Surgery, University of Chicago, Chicago, Illinois.
authors.forename: Mark K
authors.initials: MK
authors.lastname: Ferguson
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008198:Lymph Nodes / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D019043:Vascular Neoplasms / Q000473:pathology*