International Center-Level Variation in Utilization of Completion Lymph Node Dissection and Adjuvant Systemic Therapy for Sentinel Lymph Node-Positive Melanoma at Major Referral Centers

Abstract

Objective: The aim of this study was to determine overall trends and center-level variation in utilization of completion lymph node dissection (CLND) and adjuvant systemic therapy for sentinel lymph node (SLN)-positive melanoma.

Summary background data: Based on recent clinical trials, management options for SLN-positive melanoma now include effective adjuvant systemic therapy and nodal observation instead of CLND. It is unknown how these findings have shaped practice or how these contemporaneous developments have influenced their respective utilization.

Methods: We performed an international cohort study at 21 melanoma referral centers in Australia, Europe, and the United States that treated adults with SLN-positive melanoma and negative distant staging from July 2017 to June 2019. We used generalized linear and multinomial logistic regression models with random intercepts for each center to assess center-level variation in CLND and adjuvant systemic treatment, adjusting for patient and disease-specific characteristics.

Results: Among 1109 patients, performance of CLND decreased from 28% to 8% and adjuvant systemic therapy use increased from 29 to 60%. For both CLND and adjuvant systemic treatment, the most influential factors were nodal tumor size, stage, and location of treating center. There was notable variation among treating centers in management of stage IIIA patients and use of CLND with adjuvant systemic therapy versus nodal observation alone for similar risk patients.

Conclusions: There has been an overall decline in CLND and simultaneous adoption of adjuvant systemic therapy for patients with SLN-positive melanoma though wide variation in practice remains. Accounting for differences in patient mix, location of care contributed significantly to the observed variation.

Figure 1.. Proportion of patients who underwent completion lymph node dissection and received adjuvant systemic therapy before and after DeCOG-SLT and MSLT-2 publication and region-specific regulatory approvals of adjuvant immunotherapies and BRAF/MEK inhibitor therapy

*Historical rates of CLND for years 2012 and 2016 and of adjuvant systemic therapy for 2016 for resected stage III melanoma were obtained from the National Cancer Database; historical rate of adjuvant systemic therapy from 2012 derived from MSLT-II and DeCOG-SLT publications Abbreviations: DeCOG-SLT = German Dermatologic Oncology Group Trial; MSLT-II = Second Multicenter Selective Lymphadenectomy Trial; FDA = United States Food and Drug Administration; EMA = European Medicines Agency (Europe); NICE = National Institute for Healthcare Excellence (United Kingdom); PBAC = Pharmaceutical Benefits Advisory Committee (Australia); Dab/tram = dabrafenib/trametinib

Figure 2.. Nodal management with observation versus completion lymph node dissection (CLND) and adjuvant systemic therapy use for patients with melanoma treated at twenty-one participating institutions in Australia, Europe, and the United States

Figure 3:. Probability of completion lymph node dissection (CLND) and adjuvant systemic treatment by treating center^a

^aAdjusted for primary tumor site, ulceration, AJCC 8^th edition stage, size of largest nodal tumor deposit, microsatellitosis, and extranodal tumor extension; models contained random intercept to account for clustering of patients within facility.

Figure 4.. Nodal management and adjuvant systemic therapy for AJCC 8^th Edition Stage IIIA (A) versus Stage IIIB-D (B) melanoma patients based on region of treating center

AJCC = American Joint Committee on Cancer; CLND=completion lymph node dissection; USA =United States of America