Original Articles

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

Broman, Kristy K. MD, MPH^*,†,‡; Hughes, Tasha M. MD, MPH^§; Bredbeck, Brooke C. MD^§; Sun, James MD^*; Kirichenko, Dennis MS^†; Carr, Michael J. MD^*; Sharma, Avinash MD^¶; Bartlett, Edmund K. MD^¶; Nijhuis, Amanda A.G. MD, PhD^||; Thompson, John F. MD^||; Hieken, Tina J. MD^**; Kottschade, Lisa CNP^**; Downs, Jennifer MD^††; Gyorki, David E. MBBS, MD^††; Stahlie, Emma MD^‡‡; van Akkooi, Alexander MD, PhD^‡‡; Ollila, David W. MD^§§; O’shea, Kristin MEd^§§; Song, Yun MD^¶¶¶; Karakousis, Giorgos MD^¶¶; Moncrieff, Marc MD^||||; Nobes, Jenny FRCR^||||; Vetto, John MD^***; Han, Dale MD^***; Hotz, Meghan MD^†††; Farma, Jeffrey M. MD^†††; Deneve, Jeremiah L. DO^‡‡‡; Fleming, Martin D. MD^‡‡‡; Perez, Matthew MD^§§§; Baecher, Kirsten MD^§§§; Lowe, Michael MD^§§§; Bagge, Roger Olofsson MD, PhD^¶¶¶¶; Mattsson, Jan MD, PhD^¶¶¶¶; Lee, Ann Y. MD^||||||; Berman, Russell S. MD^||||||; Chai, Harvey^****; Kroon, Hidde M. MD, PhD^****; Teras, Juri MD, PhD^††††; Teras, Roland M. MD^††††; Farrow, Norma E. MD, MHS^‡‡‡‡; Beasley, Georgia M. MD, MHS^‡‡‡‡; Hui, Jane Yuet Ching MD, MS^§§§§; Been, Lukas MD, PhD^¶¶¶¶¶; Kruijff, Schelto MD, PhD^¶¶¶¶¶; Sinco, Brandy MS^§; Sarnaik, Amod A. MD^*,†; Sondak, Vernon K. MD^*,†; Zager, Jonathan S. MD^*,†; Dossett, Lesly A. MD, MPH^§; for the International High Risk Melanoma Consortium

Author Information

^*Moffitt Cancer Center, Tampa, FL

^†University of South Florida Morsani College of Medicine, Tampa, FL

^‡University of Alabama at Birmingham, Birmingham, AL

^§University of Michigan, Ann Arbor, MI

^¶Memorial Sloan Kettering Cancer Center, New York, NY

^||Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia

^**Mayo Clinic, Rochester, MN

^††Peter MacCallum Cancer Center, Melbourne, Australia

^‡‡Netherlands Cancer institute, Amsterdam, The Netherlands

^§§University of North Carolina, Chapel Hill, NC

^¶¶University of Pennsylvania, Philadelphia, PA

^||||Norfolk and Norwich University Hospital, Norwich, United Kingdom

^***Oregon Health & Science University, Portland, OR

^†††Fox Chase Cancer Center, Philadelphia, PA

^‡‡‡University of Tennessee, Memphis, TN

^§§§Emory University, Atlanta, GA

^¶¶¶University of Gothenburg, Gothenburg, Sweden

^||||||NYU Langone Health, New York, NY

^****Royal Adelaide Hospital, University of Adelaide, Adelaide, Australia

^††††North Estonia Medical Centre Foundation, Tallinn, Estonia

^‡‡‡‡Duke University, Durham, NC

^§§§§University of Minnesota, Minneapolis, MN

^¶¶¶¶University Medical Center, Groningen, Netherlands

[email protected].

L.A.D. and J.S.Z. served as co-senior authors.

Disclosures: G.M.B. is a consultant for Regeneron and receives clinical trial funding from Istari Oncology.

B.C.B. is supported by the Ruth L. Kirschstein Research Service Award from the National Cancer Institute (NCI; T32 CA009672); J.M.F. is a speaker for Novartis and serves on the Data Safety Monitoring Board for Delcath; D.E.G. has received honoraria from Amgen, Bayer, and Qbiotics. He has served on the advisory board for Amgen; T.J.H. has received research funding from Genentech and the Breast Cancer Research Foundation; L.K. was received research funding from Bristol-Meyers Squibb and serves on the advisory board for Novartis; R.O.B. has received institutional research grants from Astra Zeneca, Bristol-Myers Squibb (BMS) and SkyLineDx, speaker honorarium from Roche and Pfizer and has served on advisory boards for Amgen, BD/BARD, Bristol-Myers Squibb (BMS), Merck Sharp & Dohme (MSD), Novartis, Roche and Sanofi Genzyme; A.A.S. is a consultant to Iovance Biotherapeutics, Guidepoint, Defined Health, and Gerson Lehman group. His institution has received research funding from Iovance Biotherapeutics and Provectus Inc. He has received speaker fees from Physicians’ Education Resource and Medscape; V.K.S. is a paid consultant to Merck, Bristol Myers Squibb, Novartis, Regeneron, Array, Replimune, Pfizer, Genentech/Roche, Eisai, Aduro, Amgen, TRM Oncology, and Polynoma; J.F.T. is supported by the National Health and Medical Research Council (Grant #APP1093017). He has received honoraria for advisory board participation from Bristol Meyers Squibb Australia, Glaxo Smith Kline, Merck Sharp & Dohme Australia, Provectus. He has received travel support from Glaxo Smith Kline and Provectus; A.V. had received honoraria and/or served on advisory boards for Amgen, Bristol Myers Squibb, Novartis, MSD-Merck, Merck-Pfizer, Sanofi, and 4SC. He has received research grants from Amgen and Merck-Pfizer; J.V. is a consultant for Castle Biosciences.

J.S.Z. has received research funding from Novartis, Philogen, Delcath Systems, Amgen, Provectus, Novartis and Castle Biosciences. He has served on Advisory Boards for Merck, Novartis and Pfizer and on the Speakers Bureau for Pfizer, Sun Pharma, and Castle Biosciences. He provides expert testimony to McGowan Hood and Bubalo Law.

All other authors reported no disclosures.

Author contributions: K.K.B.—conception and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript, critical revisions, statistical analysis; T.M.H.—acquisition of data, critical revisions; B.C.B.— conception and design, analysis and interpretation of data, drafting of the manuscript, critical revisions; J.S.—conception and design, acquisition of data, analysis and interpretation of data, critical revisions; D.K.—conception and design, acquisition of data, critical revisions; M.J.C.—conception and design, acquisition of data, critical revisions; A.S.—acquisition of data, analysis and interpretation of data, critical revisions; E.K.B.—analysis and interpretation of data, critical revisions, supervision; A.A.G.N.—acquisition of data, analysis and interpretation of data, critical revisions; J.F.T.—conception and design, analysis and interpretation of data, critical revisions, supervision; T.J.H.—conception and design, acquisition of data, analysis and interpretation of data, critical revisions; L.K.—conception and design, acquisition of data, critical revisions; J.D.—conception and design, acquisition of data, critical revisions; D.E.G.—conception and design, acquisition of data, analysis and interpretation of data, critical revisions, supervision; E.S.—conception and design, acquisition of data, critical revisions; A.V.—conception and design, analysis and interpretation of data, critical revisions, supervision; D.W.O.—conception and design, critical revisions, supervision; K.O.—acquisition of data, critical revisions; Y.S.—conception and design, acquisition of data, critical revisions; G.K.—conception and design, critical revisions; M.M.—acquisition of data, critical revisions; J.N.—acquisition of data, critical revisions; J.V.—conception and design, acquisition of data, critical revisions; D.H.—conception and design, acquisition of data, analysis and interpretation of data, critical revisions; J.M.F.—conception and design, acquisition of data, analysis and interpretation of data, critical revisions; M.H.—acquisition of data, critical revisions; J.L.D.—conception and design, acquisition of data, critical revisions; M.D.F.—conception and design, acquisition of data, critical revisions; M.P.—conception and design, acquisition of data, critical revisions; K.B.—conception and design, acquisition of data, critical revisions; M.L.—conception and design, acquisition of data, analysis and interpretation of data, critical revisions; R.O.B.—conception and design, acquisition of data, analysis and interpretation of data, critical revisions; J.M.—conception and design, acquisition of data, critical revisions; A.Y.L.—conception and design, acquisition of data, analysis and interpretation of data, critical revisions; R.S.B.—conception and design, acquisition of data, critical revisions; H.C.—acquisition of data, critical revisions; H.M.K.—conception and design, acquisition of data, analysis and interpretation of data, critical revisions; J.T.—conception and design, acquisition of data, critical revisions; R.M.T.—conception and design, acquisition of data, critical revisions; N.E.F.—conception and design, acquisition of data, critical revisions; G.B.—conception and design, critical revisions, analysis and interpretation of data, supervision; J.Y.C.H.—conception and design, acquisition of data, critical revisions; L.B.—conception and design, acquisition of data, critical revisions; S.K.—conception and design, acquisition of data, critical revisions; B.S.—conception and design, analysis and interpretation of data, statistical analysis; A.S.—conception and design, analysis and interpretation of data, critical revisions; V.K.S.—conception and design, analysis and interpretation of data, critical revisions; J.S.Z.—conception and design, analysis and interpretation of data, critical revisions, supervision; L.A.D.—conception and design, critical revisions, supervision

The authors report no conflicts of interest.

Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website, www.annalsofsurgery.com.

Annals of Surgery 277(5):p e1106-e1115, May 2023. | DOI: 10.1097/SLA.0000000000005370

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.

Article Keywords

Keywords
active surveillance, adjuvant therapy, completion lymph node dissection, de-implementation, implementation science, melanoma, sentinel lymph node

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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