ASCO/SSO支持黑色素瘤前哨淋巴结活检

7月9日，美国临床肿瘤学会(ASCO)和美国肿瘤外科学会(SSO)联合发布的一份新指南建议，所有新近确诊为黑色素瘤且肿瘤为中等厚度(定义为Breslow厚度介于1~4 mm)的患者都应接受前哨淋巴结活检(SLNB)。对于肿瘤更厚或更薄的黑色素瘤患者而言，虽然SLNB的价值目前尚存争议，但在某些情况下这两类患者都会受益于SLNB。

指南称，SLNB呈阳性的所有黑色素瘤患者都应该接受完全淋巴结清扫术(CLND)，这是目前的标准处理办法，尽管尚不清楚这样做是否能改善患者的10年总生存率。正在进行中的大规模随机试验“多中心选择性淋巴结清扫术试验II (MSLT-Ⅱ)”将会解答这一问题。

在密歇根大学Sandra L. Wong博士和杜克大学Gary H. Lyman博士的带领下，这份指南的作者希望利用最新的研究证据来确定前哨淋巴结活检用于黑色素瘤患者的适应证以及完全活检的作用。他们认为：“非常有必要确定，对于哪些患者而言切除局部淋巴结的预期效益大于潜在的手术风险。”

为此，Wong博士、Lyman博士以及另外12名专家组成员进行了全面的文献检索，最终符合Meta分析纳入标准的研究有73项(大部分为观察性研究)，共涉及患者约25,000例。

作者发现，虽然有充分的证据支持中等厚度的黑色素瘤患者常规使用SLNB，但也有一些证据支持当存在其他某些危险因素时，肿瘤厚度＜1 mm以及＞4 mm的患者也接受SLNB。

对于Breslow厚度＜1 mm的黑色素瘤患者，如果存在≥1个危险因素，比如肿瘤溃疡形成或有丝分裂率≥1/mm²，那么“病理分期的获益可能超过潜在的手术风险”，尤其是对于肿瘤厚度介于0.75~0.99 mm的黑色素瘤患者亚组。

Breslow厚度≥4 mm的黑色素瘤患者也可能受益于SLNB。作者写道：“传统观点认为黑色素瘤偏厚的患者在确诊时已经存在全身性疾病的风险较高，因此清扫局部淋巴结的生存获益不大。”“然而，对于没有远处转移的患者而言，即便黑色素瘤偏厚也应和中等厚度的黑色素瘤患者一样行SLNB，对于这类患者SLNB作为一项病理分期操作也能发挥同样的效果。黑色素瘤偏厚的患者接受SLNB的主要优势之一是可以更好地控制局部疾病。”

这份指南重申CLND仍应该视为SLNB肿瘤阳性患者的标准治疗，即便正在进行中的MSLT-Ⅱ试验尚未得出生存率方面的数据。作者还引用了支持这一结论的研究证据，CLND后淋巴结复发率约为4.2%~4.9%，而Wong博士及其同事在先前一项研究中报告称，在没有行CLND的患者中，局部淋巴结复发作为首个转移部位的患者比例达到了15%，局部淋巴结总复发率则高达41%(Ann Surg Oncol 2006 13:302-309)。

作者写道：“在MSLT-Ⅱ试验得出最终结果之前，我们还没有高级别的证据来确定CLND对于局部疾病控制的价值。现有最佳证据表明，对于大部分SLNB阳性患者，CLND可以有效地控制局部疾病。”

这份指南由ASCO和SSO委托制定。作者声明无相关利益冲突。

爱思唯尔  版权所有

By: JENNIE SMITH,  Oncology Report Digital Network

All newly diagnosed melanoma patients with tumors of intermediate thickness – defined as those with a Breslow thickness of between 1 and 4 mm – should undergo sentinel lymph node biopsy, according to a new guideline from two professional societies.

The guideline, issued jointly July 9 by the American Society of Clinical Oncology and the Society of Surgical Oncology, also advises that while the use of sentinel lymph node biopsy (SLNB) in people with thicker or thinner melanomas remains contentious, both categories of patients could benefit from SLNB in some circumstances.

All melanoma patients with a positive SLNB, the guideline says, should be treated with completion lymph node dissection (CLND), the current standard of care, although, the authors noted, it is not yet known whether CLND after a positive SLN biopsy improves 10-year overall survival. This is the subject of a large, ongoing randomized trial, the Multicenter Selective Lymphadenectomy Trial II (MSLT-11).

The guideline’s authors, led by Dr. Sandra L. Wong of the University of Michigan, Ann Arbor, and Dr. Gary H. Lyman of Duke University, Durham, N.C., aimed to use the most current evidence to clarify both the indications for sentinel node biopsy and the role of completion biopsy in people with melanomas.

"It is critically important to identify those patients for whom the expected benefits of resecting regional lymph nodes outweigh the risks of surgical morbidity," they wrote in their analysis.

To this end, Dr. Wong, Dr. Lyman, and 12 other expert panel members undertook a broad literature search and identified 73 studies (most of them observational in design) that met the criteria for inclusion in their meta-analysis. Some 25,000 patients were enrolled in the included studies.

The authors found that while robust evidence supports routine use of sentinel lymph node biopsy (SLNB) in intermediate melanomas, there is also some evidence to support the procedure in patients with thin melanomas (less than 1 mm) when certain other risk factors are present, and in patients with thick melanomas (greater than 4 mm).

For people with melanomas of less than 1 mm Breslow thickness and one or more risk factors such as tumor ulceration or a mitotic rate of 1/mm2 or greater, they wrote, "the benefits of pathologic staging may outweigh the potential risks of the procedure," particularly in the subgroup of patients with melanomas ranging from 0.75 mm to 0.99 mm.

Patients with melanomas of 4 mm or greater may also benefit, the guideline says. "Conventional wisdom asserts that patients with thick melanomas have a high risk of systemic disease at the time of diagnosis and that no survival benefit can be derived from removal of regional lymph nodes," the authors wrote.

"However, among patients without distant disease, it can be argued that those with thick melanomas have indications for SLN biopsy similar to those of patients with intermediate-thickness melanomas and derive the same benefits from SLN biopsy as a pathologic staging procedure. One of the main advantages of SLN biopsy in patients with thick melanomas is better regional disease control."

The guideline reiterates that CLND should remain the standard of care for patients with tumor-positive SLNs, even absent survival data from the ongoing MSLT-II trial. The authors cited in support of this evidence from studies that saw nodal recurrence after CLND of between 4.2% and 4.9%. By contrast, as Dr. Wong and colleagues reported in an earlier study, patients in whom CLND was not performed saw a 15% rate of regional nodal recurrence as a site of first metastasis and 41% overall regional nodal recurrence rate (Ann Surg Oncol 2006 13:302-309).

"Until final results of MSLT-II are available, we will not be able to determine, with higher-level evidence, the impact of CLND on regional disease control. Until that time, the best available evidence suggests that CLND is effective at achieving regional disease control in the majority of patients with positive SLNs," the authors wrote.

The guideline was commissioned by ASCO and SSO. The authors disclosed no conflicts of interest.