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前哨淋巴结阳性黑色素瘤患者的主动监测:多中心选择性淋巴结清扫试验 II (MSLT-2) 后采用和早期结果的国际多机构评估。

Active surveillance of patients who have sentinel node positive melanoma: An international, multi-institution evaluation of adoption and early outcomes after the Multicenter Selective Lymphadenectomy Trial II (MSLT-2).

机构信息

Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida.

Department of Oncologic Sciences, University of South Florida Morsani School of Medicine, Tampa, Florida.

出版信息

Cancer. 2021 Jul 1;127(13):2251-2261. doi: 10.1002/cncr.33483. Epub 2021 Apr 7.

Abstract

BACKGROUND

For patients with sentinel lymph node (SLN)-positive cutaneous melanoma, the Second Multicenter Selective Lymphadenectomy trial demonstrated equivalent disease-specific survival (DSS) with active surveillance using nodal ultrasound versus completion lymph node dissection (CLND). Adoption and outcomes of active surveillance in clinical practice and in adjuvant therapy recipients are unknown.

METHODS

In a retrospective cohort of SLN-positive adults treated at 21 institutions in Australia, Europe, and the United States from June 2017 to November 2019, the authors evaluated the impact of active surveillance and adjuvant therapy on all-site recurrence-free survival (RFS), isolated nodal RFS, distant metastasis-free survival (DMFS), and DSS using Kaplan-Meier curves and Cox proportional hazard models.

RESULTS

Among 6347 SLN biopsies, 1154 (18%) were positive and had initial negative distant staging. In total, 965 patients (84%) received active surveillance, 189 (16%) underwent CLND. Four hundred thirty-nine patients received adjuvant therapy (surveillance, 38%; CLND, 39%), with the majority (83%) receiving anti-PD-1 immunotherapy. After a median follow-up of 11 months, 220 patients developed recurrent disease (surveillance, 19%; CLND, 22%), and 24 died of melanoma (surveillance, 2%; CLND, 4%). Sixty-eight patients had an isolated nodal recurrence (surveillance, 6%; CLND, 4%). In patients who received adjuvant treatment without undergoing prior CLND, all isolated nodal recurrences were resectable. On risk-adjusted multivariable analyses, CLND was associated with improved isolated nodal RFS (hazard ratio [HR], 0.36; 95% CI, 0.15-0.88), but not all-site RFS (HR, 0.68; 95% CI, 0.45-1.02). Adjuvant therapy improved all-site RFS (HR, 0.52; 95% CI, 0.47-0.57). DSS and DMFS did not differ by nodal management or adjuvant treatment.

CONCLUSIONS

Active surveillance has been adopted for most SLN-positive patients. At initial assessment, real-world outcomes align with randomized trial findings, including in adjuvant therapy recipients.

LAY SUMMARY

For patients with melanoma of the skin and microscopic spread to lymph nodes, monitoring with ultrasound is an alternative to surgically removing the remaining lymph nodes. The authors studied adoption and real-world outcomes of ultrasound monitoring in over 1000 patients treated at 21 centers worldwide, finding that most patients now have ultrasounds instead of surgery. Although slightly more patients have cancer return in the lymph nodes with this strategy, typically, it can be removed with delayed surgery. Compared with up-front surgery, ultrasound monitoring results in the same overall risk of melanoma coming back at any location or of dying from melanoma.

摘要

背景

对于 SLN 阳性皮肤黑色素瘤患者,第二多中心选择性淋巴结清扫试验表明,主动监测与淋巴结超声联合使用与完成淋巴结清扫术(CLND)相比,具有同等的疾病特异性生存(DSS)。主动监测在临床实践中的采用和辅助治疗接受者的结果尚不清楚。

方法

在 2017 年 6 月至 2019 年 11 月期间,在澳大利亚、欧洲和美国的 21 个机构中治疗的 SLN 阳性成年人的回顾性队列中,作者使用 Kaplan-Meier 曲线和 Cox 比例风险模型评估了主动监测和辅助治疗对所有部位无复发生存(RFS)、孤立淋巴结 RFS、远处转移无复发生存(DMFS)和 DSS 的影响。

结果

在 6347 例 SLN 活检中,1154 例(18%)呈阳性且初始远处分期阴性。共有 965 名患者(84%)接受了主动监测,189 名患者(16%)接受了 CLND。439 名患者接受了辅助治疗(监测,38%;CLND,39%),其中大多数(83%)接受了抗 PD-1 免疫治疗。中位随访 11 个月后,220 名患者出现复发性疾病(监测,19%;CLND,22%),24 名患者死于黑色素瘤(监测,2%;CLND,4%)。68 名患者出现孤立性淋巴结复发(监测,6%;CLND,4%)。在未接受 CLND 治疗的接受辅助治疗的患者中,所有孤立性淋巴结复发均可切除。在风险调整后的多变量分析中,CLND 与改善的孤立淋巴结 RFS 相关(HR,0.36;95%CI,0.15-0.88),但与所有部位 RFS 无关(HR,0.68;95%CI,0.45-1.02)。辅助治疗改善了所有部位的 RFS(HR,0.52;95%CI,0.47-0.57)。DSS 和 DMFS 不受淋巴结管理或辅助治疗的影响。

结论

主动监测已被大多数 SLN 阳性患者采用。在初始评估时,真实世界的结果与随机试验结果一致,包括在辅助治疗接受者中。

医生解读

对于皮肤黑色素瘤且有淋巴结微转移的患者,通过超声监测是替代手术切除剩余淋巴结的一种选择。作者研究了全球 21 个中心的 1000 多名患者接受超声监测的采用情况和真实世界结果,发现大多数患者现在都接受了超声检查而不是手术。尽管这种策略会导致更多的患者淋巴结内癌症复发,但通常可以通过延迟手术切除。与 upfront 手术相比,超声监测在任何部位黑色素瘤复发或死于黑色素瘤的总体风险上没有差异。

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