title: The impact of surgery on survival of patients with cutaneous melanoma: revisiting the role of primary tumor excision margins.
abstract: OBJECTIVE
  To quantify the impact of excision margins on disease-specific survival of patients with primary cutaneous melanoma.
  
  
  BACKGROUND
  Current guidelines recommend narrow margins for the treatment of primary melanoma, although available evidence on this subject is not unequivocal and not always appropriately analyzed.
  
  
  METHODS
  A systematic review of randomized controlled trials (RCT) addressing the issue of wide versus narrow excision margins was performed. Meta-analysis methods for time-to-event data were used to extract hazard ratios(HR) and their 95% confidence intervals (CI) from eligible studies, and ultimately to estimate the summary effect of excision margins on patients' survival.
  
  
  RESULTS
  The 5 eligible RCT enrolled a total of 3295 patients who were allocated to wide (3-5 cm) or narrow (1-2 cm) excision of their primary tumor. The data of locoregional disease-free (LDFS), disease-free (DFS),disease-specific (DSS), and overall (OS) survival were available for 3, 5, 3, and 5 RCT, respectively. The meta-analysis suggested that narrow margins might be associated with an increased risk of both locoregional disease recurrence (HR: 1.30, CI: 1.07-1.57; P = 0.01) and death by disease (HR: 1.28, CI:1.07-1.53, P = 0.01). As regards DFS, the borderline disadvantage (HR:1.13, CI: 0.995-1.28; P = 0.06) becomes significant when considering RCT that enrolled patients with thicker melanoma (HR: 1.19, CI: 1.02-1.39, P =0.03). When death by any cause (OS) was analyzed, no risk difference was found.
  
  
  CONCLUSIONS
  The lack of DSS data from all the available RCT does not allow to draw definitive conclusions. However, current evidence appears sufficient to question the common belief that narrow excision margins are as safe as wide margins in the management of primary melanoma, that calls for further investigation in this field.
authors.affiliation: Department of Oncological and Surgical Sciences, Meta-analysis Unit, University of Padova, via Giustiniani 2, Padua, Italy. simone.mocellin@unipd.it
authors.forename: Simone
authors.initials: S
authors.lastname: Mocellin
authors.forename: Sandro
authors.initials: S
authors.lastname: Pasquali
authors.forename: Donato
authors.initials: D
authors.lastname: Nitti
mesh_terms: D018572:Disease-Free Survival; D006801:Humans; D008545:Melanoma / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D012878:Skin Neoplasms / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D016019:Survival Analysis; D015996:Survival Rate