Complete lymph node dissection versus no dissection in patients with sentinel lymph node biopsy positive melanoma (DeCOG-SLT): a multicentre, randomised, phase 3 trial
Complete lymph node dissection versus no dissection in patients with sentinel lymph node biopsy positive melanoma (DeCOG-SLT): a multicentre, randomised, phase 3 trial
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DOI：
10.1016/s1470-2045(16)00141-8
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发表时间：
2016-06-01
期刊：
影响因子：
51.1
通讯作者：
Garbe, Claus
中科院分区：
文献类型：
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作者：
Leiter, Ulrike;Stadler, Rudolf;Garbe, Claus
背景 对于前哨淋巴结活检结果呈阳性的患者，建议进行彻底的淋巴结清扫。迄今为止，完整淋巴结清扫对预后的影响仍存在争议。在 DeCOG-SLT 试验中，我们评估了与观察相比，完全淋巴结清扫是否会提高生存率。 方法 在这项多中心、随机、3 期试验中，我们招募了来自 41 个德国皮肤癌中心的躯干、手臂或腿部皮肤黑色素瘤患者。前哨淋巴结活检结果呈阳性的患者符合资格。患者被随机分配（1：1）接受完整的淋巴结清扫或观察不同大小的排列块，并根据原发肿瘤厚度、原发肿瘤溃疡和预期的辅助干扰素治疗进行分层。治疗分配没有被掩盖。主要终点是无远处转移生存期，并按意向治疗进行分析。完全淋巴结清扫组意向治疗人群的所有患者均纳入安全性分析。该试验已在 ClinicalTrials.gov 注册，编号为 NCT02434107。随访仍在进行中，但该试验不再招募患者。 结果在2006年1月1日至2014年12月1日期间，对5547名患者进行了前哨淋巴结活检筛查，其中1269名（23%）患者微转移呈阳性。其中，483 名 (39%) 同意随机进入临床试验；由于入组困难和事件发生率低，该试验于 2014 年 12 月 1 日提前结束。241 名患者被随机分配到观察组，242 名患者被分配到完全淋巴结清扫组。 10例患者不符合纳入标准，因此观察组分析233例患者，彻底淋巴结清扫组分析240例患者，作为意向治疗人群。 311 例（66%）患者（观察组 158 例，清扫组 153 例）的前哨淋巴结转移小于 1 mm。中位随访时间为 35 个月（IQR 20-54）。观察组3年无远处转移生存率为77.0%（90% CI 71.9-82.1；55个事件），而完全淋巴结清扫组为74.9%（69.5-80.3；54个事件）。在完全淋巴结清扫组中，分别有 15 名患者（6%）和 19 名患者（8%）发生 3 级和 4 级事件。不良事件包括淋巴水肿（7名患者为3级，13名患者为4级）、淋巴瘘（1名患者为3级，2名患者为4级）、血清肿（3名患者为3级，无4级）、感染（3名患者为3级，无4级）和伤口愈合延迟（1名患者为3级，4名患者为4级）；没有报告严重的不良事件。 解释 尽管我们没有达到所需的事件数量，导致试验动力不足，但我们的结果显示，与仅观察相比，接受完全淋巴结清扫治疗的患者的生存率没有差异。因此，对于淋巴结微转移直径至少为 1 毫米或更小的黑色素瘤患者，不建议进行完全淋巴结清扫。
Background Complete lymph node dissection is recommended in patients with positive sentinel lymph node biopsy results. To date, the effect of complete lymph node dissection on prognosis is controversial. In the DeCOG-SLT trial, we assessed whether complete lymph node dissection resulted in increased survival compared with observation.Methods In this multicentre, randomised, phase 3 trial, we enrolled patients with cutaneous melanoma of the torso, arms, or legs from 41 German skin cancer centres. Patients with positive sentinel lymph node biopsy results were eligible. Patients were randomly assigned (1: 1) to undergo complete lymph node dissection or observation with permuted blocks of variable size and stratified by primary tumour thickness, ulceration of primary tumour, and intended adjuvant interferon therapy. Treatment assignment was not masked. The primary endpoint was distant metastasis-free survival and analysed by intention to treat. All patients in the intention-to-treat population of the complete lymph node dissection group were included in the safety analysis. This trial is registered with ClinicalTrials.gov, number NCT02434107. Follow-up is ongoing, but the trial no longer recruiting patients.Findings Between Jan 1, 2006, and Dec 1, 2014, 5547 patients were screened with sentinel lymph node biopsy and 1269 (23%) patients were positive for micrometastasis. Of these, 483 (39%) agreed to randomisation into the clinical trial; due to difficulties enrolling and a low event rate the trial closed early on Dec 1, 2014. 241 patients were randomly assigned to the observation group and 242 to the complete lymph node dissection group. Ten patients did not meet the inclusion criteria, so 233 patients were analysed in the observation group and 240 patients were analysed in the complete lymph node dissection group, as the intention-to-treat population. 311 (66%) patients (158 in the observation group and 153 in the dissection group) had sentinel lymph node metastases of 1 mm or less. Median follow-up was 35 months (IQR 20-54). Distant metastasis-free survival at 3 years was 77.0% (90% CI 71.9-82.1; 55 events) in the observation group and 74.9% (69.5-80.3; 54 events) in the complete lymph node dissection group. In the complete lymph node dissection group, grade 3 and 4 events occurred in 15 patients (6%) and 19 patients (8%) patients, respectively. Adverse events included lymph oedema (grade 3 in seven patients, grade 4 in 13 patients), lymph fistula (grade 3 in one patient, grade 4 in two patients), seroma (grade 3 in three patients, no grade 4), infection (grade 3 in three patients, no grade 4), and delayed wound healing (grade 3 in one patient, grade 4 in four patients); no serious adverse events were reported.Interpretation Although we did not achieve the required number of events, leading to the trial being underpowered, our results showed no difference in survival in patients treated with complete lymph node dissection compared with observation only. Consequently, complete lymph node dissection should not be recommended in patients with melanoma with lymph node micrometastases of at least a diameter of 1 mm or smaller.