Long-term Follow-up of Survival in Surgical Resected Invasive Cutaneous Melanomas: Comparing 2-cm Versus 4 -cm Resection Margins - a Randomized, Multicenter Trial

Historically, CMMs have been excised with wide resection margins of 5-cm or more with the radical removal of lymph nodes. This treatment emerged from a recommendation from Handley in 1907 based on a single pathological specimen. This "radical" surgical management resulted in bad cosmetic results, lymphedema, long hospital inpatient stay, frequent skin grafting and/or complicated skin flap reconstructions. Not until some 60-plus years later did questions arise in clinical practices whether the need for this extensive surgery was mandated and clinical practice was not substantially changed until the late 1980's. Retrospective studies published in the 1980s suggested that narrower excision margins may be appropriate for treatment of some CMMs, especially thinner lesions.

Nowadays, the recommendations for surgical treatment are based on the Breslow thickness of the CMM, since it is considered the most important prognostic indicator of localized disease and is therefore the information upon which today's surgical strategies are founded. However, recommendations vary over the world, especially for thicker tumors which is clearly presented by Ethun et al. (2016). For CMM of ≤ 1 mm thickness most centers use a 1 cm margin, but for tumors 1.01 - 4 mm the margins of resection are 1-3 cm depending on the country. Most patients with primary CMM > 4 mm are operated on with a margin of 2-cm today. The different national guidelines are thus, somewhat confusing and in a report from 2004 Thomas JM et al. showed that a 1-cm margin for CMM with a poor prognosis (≥2 mm) is associated with a greater risk of regional recurrence than in a 3-cm margin, but with a similar survival rate.

Today, according to Sladden et al. (2018), there have been published six randomized controlled trials (RCTs) assessing outcomes for surgical excision margins based upon Breslow thickness of invasive tumors. Three out of those six RCTs have included patients with CMMs 2-4 cm thick. Still, there are controversies and this report points out gaps of knowledge, e.g. lack of evidence about the optimal depth of excision and the optimal and minimal excision margins, since 1-cm versus 2-cm resection margins of invasive CMMs have not been directly compared yet.

Interestingly, out of one of the three RCTs analyzing melanomas with 2-4 mm thickness, long-term follow up data has recently been published by Hayes et al. 2016. They report an extended follow-up with a median follow-up of almost 9 years, concluding that 1-cm margin is not safe for high-risk CMMs compared to 3-cm margin.

From this point, based up on those interesting results, the investigators now present long-term follow-up of survival in patients included in the RCT published 2011 by Gillgren et al.