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.

Keywords: Bayesian; Margin; Melanoma; Meta-analysis; Survival; Systematic review.