近日，瑞典卡罗林斯卡医学院教授Peter Gillgren及其研究团队对2厘米手术切缘与4厘米手术切缘治疗原发性皮肤黑色素瘤进行了一项多中心、随机试验的长期随访。 相关论文于2019年8月10日发表在《柳叶刀》杂志上。
在他们之前的一项多中心随机对照试验报告中，中位随访6.7年后发现较小的切除范围（2厘米对4厘米）并不影响黑色素瘤特异性生存率和总体生存率。之后该课题组对这项试验延长了随访时间。
在这项开放标签、多中心随机对照试验中，该课题组从瑞典、丹麦、爱沙尼亚和挪威的53家医院招募患者。这些临床分期患者的年龄均在75岁及以下，被诊断为局部皮肤黑色素瘤，且厚度大于2毫米，原发部位位于躯干、上肢或下肢。患者被随机分组(1:1)接受2厘米切缘或4厘米切缘的手术治疗。医生在对皮肤黑色素瘤厚度大于2毫米进行组织病理学确定后将这些患者登记入组，并负责患者的临床护理和试验研究（随访、数据收集和撰写论文）。在其他情况下，医生不接触患者。随机分组方法采用致电随机化办公室，密封信封，或使用排列区块生成列表来完成。患者按地理区域进行分类，试验的所有部分均公开透明。这项长期随访的主要研究指标是总体生存率和黑色素瘤特异性生存率。所有分析均基于意向治疗原则。
从1992年1月22日至2004年5月19日，该课题组共招募了936例临床分期患者，随机分为4厘米切缘组(465例)和2厘米切缘组(471例)。中位总体随访19.6年后，共有621例患者死亡，其中2厘米切缘组304例(49%)，4厘米切缘组317例(51%)。共有397例患者死于皮肤黑色素瘤，其中2厘米切缘组192例(48%)，4厘米切缘组205例(52%)，差异无统计学意义。该结果表明，对于局部皮肤黑色素瘤厚度超过2毫米的患者，2厘米手术切缘是安全的，值得临床推广。
据了解，对于局部皮肤黑色素瘤厚度超过2毫米的患者，最佳手术切除范围尚不确定。
附：英文原文
Title: 2-cm versus 4-cm surgical excision margins for primary cutaneous melanoma thicker than 2 mm: long-term follow-up of a multicentre, randomised trial
Author: Deborah Utjés, Jonas Malmstedt, Jüri Teras, Prof Krzysztof Drzewiecki, Hans Petter Gullestad, Prof Christian Ingvar, Hanna Eriksson, Peter Gillgren
Issue&Volume: VOLUME 394, ISSUE 10197, P471-477, AUGUST 10, 2019
Summary:
Background
The optimal surgical excision margins are uncertain for patients with thick (>2 mm) localised cutaneous melanomas. In our previous report of this multicentre, randomised controlled trial, with a median follow-up of 6·7 years, we showed that a narrow excision margin (2 cm vs 4 cm) did not affect melanoma-specific nor overall survival. Here, we present extended follow-up of this cohort.
Methods
In this open-label, multicentre randomised controlled trial, we recruited patients from 53 hospitals in Sweden, Denmark, Estonia, and Norway. We enrolled clinically staged patients aged 75 years or younger diagnosed with localised cutaneous melanoma thicker than 2 mm, and with primary site on the trunk or upper or lower extremities. Patients were randomly allocated (1:1) to treatment either with a 2-cm or a 4-cm excision margin. A physician enrolled the patients after histological confirmation of a cutaneous melanoma thicker than 2 mm. Some patients were enrolled by a physician acting as responsible for clinical care and as a trial investigator (follow-up, data collection, and manuscript writing). In other cases physicians not involved in running the trial enrolled patients. Randomisation was done by telephone call to a randomisation office, by sealed envelope, or by computer generated lists using permuted blocks. Patients were stratified according to geographical region. No part of the trial was masked. The primary outcome in this extended follow-up study was overall survival and the co-primary outcome was melanoma-specific survival. All analyses were done on an intention-to-treat basis. The study is registered with ClinicalTrials.gov, number NCT03638492.
Findings
Between Jan 22, 1992, and May 19, 2004, 936 clinically staged patients were recruited and randomly assigned to a 4-cm excision margin (n=465) or a 2-cm excision margin (n=471). At a median overall follow-up of 19·6 years (235 months, IQR 200–260), 621 deaths were reported—304 (49%) in the 2-cm group and 317 (51%) in the 4-cm group (unadjusted HR 0·98, 95% CI 0·83–1·14; p=0·75). 397 deaths were attributed to cutaneous melanoma—192 (48%) in the 2-cm excision margin group and 205 (52%) in the 4-cm excision margin group (unadjusted HR 0·95, 95% CI 0·78–1·16, p=0·61).
Interpretation
A 2-cm excision margin was safe for patients with thick (>2 mm) localised cutaneous melanoma at a follow-up of median 19·6 years. These findings support the use of 2-cm excision margins in current clinical practice.
DOI: https://doi.org/10.1016/S0140-6736(19)31132-8
Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31132-8/fulltext#
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