Keith Wheatley1, Jayne S Wilson1, Piers Gaunt1, Jerry R Marsden2. 1. 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. 2. Skin Oncology Service, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Edgbaston, Birmingham B15 2WB, United Kingdom.
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.
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: F C Wright; L H Souter; S Kellett; A Easson; C Murray; J Toye; D McCready; C Nessim; D Ghazarian; N J Look Hong; S Johnson; D P Goldstein; T Petrella Journal: Curr Oncol Date: 2019-08-01 Impact factor: 3.677
Authors: Jacqueline Dinnes; Lavinia Ferrante di Ruffano; Yemisi Takwoingi; Seau Tak Cheung; Paul Nathan; Rubeta N Matin; Naomi Chuchu; Sue Ann Chan; Alana Durack; Susan E Bayliss; Abha Gulati; Lopa Patel; Clare Davenport; Kathie Godfrey; Manil Subesinghe; Zoe Traill; Jonathan J Deeks; Hywel C Williams Journal: Cochrane Database Syst Rev Date: 2019-07-01
Authors: Naomi Chuchu; Yemisi Takwoingi; Jacqueline Dinnes; Rubeta N Matin; Oliver Bassett; Jacqueline F Moreau; Susan E Bayliss; Clare Davenport; Kathie Godfrey; Susan O'Connell; Abhilash Jain; Fiona M Walter; Jonathan J Deeks; Hywel C Williams Journal: Cochrane Database Syst Rev Date: 2018-12-04
Authors: Marc D Moncrieff; David Gyorki; Robyn Saw; Andrew J Spillane; John F Thompson; Howard Peach; Deemesh Oudit; Jenny Geh; Peter Dziewulski; Ewan Wilson; Paolo Matteucci; Rowan Pritchard-Jones; Roger Olofsson Bagge; Frances C Wright; Nic Crampton; Oliver Cassell; Navid Jallali; Adam Berger; John Kelly; Stephen Hamilton; Amer Durrani; Serigne Lo; Elizabeth Paton; Michael A Henderson Journal: Ann Surg Oncol Date: 2018-05-30 Impact factor: 5.344