title: Surgical excision margins in primary cutaneous melanoma: A meta-analysis and Bayesian probability evaluation.
abstract: BACKGROUND
  Surgery is the only curative treatment for primary cutaneous melanoma, therefore it is important to determine excision margins that minimise risk of local recurrence, distant recurrence and death.
  
  
  METHODS
  MEDLINE, EMBASE and Cochrane CENTRAL were searched from 2009 to 2015. Inclusion criteria were: population/setting - patients with primary melanoma; comparison - narrow versus wide margins; outcomes - overall survival, melanoma-specific survival, recurrence-free survival, and loco-regional recurrence; design - randomized controlled trials (RCTs). Results were pooled using meta-analysis and data explored using likelihood Bayesian probability plots.
  
  
  RESULTS
  Six RCTs with 4233 patients were included. Narrow margins were defined as 1 or 2 cm of clinically normal skin around the melanoma; wide margins as 3, 4 or 5 cm. Hazard ratios (HR) were as follows (HR>1 indicates wide margin better): overall survival 1.09 (95% CI 0.98-1.22; p=0.1); melanoma-specific survival 1.17 (CI 1.03-1.34; p=0.02); recurrence-free survival 1.08 (CI 0.97-1.20; p=0.2); loco-regional recurrence 1.10 (CI 0.96-1.26; p=0.2), with no evidence of heterogeneity between trials for any end point or within subgroup analyses. There was an 94% probability that overall survival was worse with a narrow margin and a 43% probability that it was more than 10% worse in proportional terms (i.e. HR>1.1). Probabilities that narrow margins were worse were 99%, 92% and 92% for melanoma-specific survival, recurrence-free survival and loco-regional recurrence respectively.
  
  
  CONCLUSIONS
  Contrary to recommendations in several national guidelines that narrow margins are safe, this systematic review and meta-analysis provides evidence that a narrow margin may lead to a worse outcome than a wide margin.
authors.affiliation: Cancer Research UK Clinical Trials Unit, Institute of Cancer & Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, United Kingdom.
authors.forename: Keith
authors.initials: K
authors.lastname: Wheatley
authors.affiliation: Cancer Research UK Clinical Trials Unit, Institute of Cancer & Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, United Kingdom.
authors.forename: Jayne S
authors.initials: JS
authors.lastname: Wilson
authors.affiliation: Cancer Research UK Clinical Trials Unit, Institute of Cancer & Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, United Kingdom.
authors.forename: Piers
authors.initials: P
authors.lastname: Gaunt
authors.affiliation: Skin Oncology Service, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Edgbaston, Birmingham B15 2WB, United Kingdom.
authors.forename: Jerry R
authors.initials: JR
authors.lastname: Marsden
mesh_terms: D001499:Bayes Theorem; D018572:Disease-Free Survival; D023381:Endpoint Determination; D006801:Humans; D008545:Melanoma / Q000473:pathology / Q000601:surgery*; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000517:prevention & control; D018365:Neoplasm, Residual; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D012107:Research Design; D012878:Skin Neoplasms / Q000473:pathology / Q000601:surgery*; D015996:Survival Rate
keywords: Bayesian; Margin; Melanoma; Meta-analysis; Survival; Systematic review