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. 2022 Sep 1;157(9):835-842.
doi: 10.1001/jamasurg.2022.2055.

Therapeutic Value of Sentinel Lymph Node Biopsy in Patients With Melanoma: A Randomized Clinical Trial

Multicenter Selective Lymphadenectomy Trials Study Group; Jessica S Crystal  1 , John F Thompson  2 , John Hyngstrom  3 , Corrado Caracò  4 , Jonathan S Zager  5 , Tiina Jahkola  6 , Tawnya L Bowles  7 , Elisabetta Pennacchioli  8 , Peter D Beitsch  9 , Harald J Hoekstra  10 , Marc Moncrieff  11 , Christian Ingvar  12 , Alexander van Akkooi  13 , Michael S Sabel  14 , Edward A Levine  15 , Doreen Agnese  16 , Michael Henderson  17 , Reinhard Dummer  18 , Rogerio I Neves  19   20 , Carlo Riccardo Rossi  21 , John M Kane 3rd  22 , Steven Trocha  23 , Frances Wright  24 , David R Byrd  25 , Maurice Matter  26 , Eddy C Hsueh  27 , Alastair MacKenzie-Ross  28 , Mark Kelley  29 , Patrick Terheyden  30 , Tara L Huston  31 , Jeffrey D Wayne  32 , Heather Neuman  33 , B Mark Smithers  34 , Charlotte E Ariyan  35 , Darius Desai  36 , Jeffrey E Gershenwald  37 , Shlomo Schneebaum  38 , Anja Gesierich  39 , Lisa K Jacobs  40 , James M Lewis  41 , Kelly M McMasters  42 , Cristina O'Donoghue  43 , Andre van der Westhuizen  44 , Armando Sardi  45 , Richard Barth  46 , Robert Barone  47 , J Greg McKinnon  48 , Craig L Slingluff  49 , Jeffrey M Farma  50 , Erwin Schultz  51 , Randall P Scheri  52 , Sergi Vidal-Sicart  53 , Manuel Molina  54 , Alessandro A E Testori  55 , Leland J Foshag  56 , Lisa Van Kreuningen  57 , He-Jing Wang  58 , Myung-Shin Sim  59 , Richard A Scolyer  60 , David E Elashoff  58 , Alistair J Cochran  61 , Mark B Faries  62
Affiliations

Therapeutic Value of Sentinel Lymph Node Biopsy in Patients With Melanoma: A Randomized Clinical Trial

Multicenter Selective Lymphadenectomy Trials Study Group et al. JAMA Surg. .

Erratum in

  • Errors in Byline.
    [No authors listed] [No authors listed] JAMA Surg. 2022 Sep 1;157(9):859. doi: 10.1001/jamasurg.2022.4558. JAMA Surg. 2022. PMID: 36102914 Free PMC article. No abstract available.

Abstract

Importance: Sentinel lymph node (SLN) biopsy is a standard staging procedure for cutaneous melanoma. Regional disease control is a clinically important therapeutic goal of surgical intervention, including nodal surgery.

Objective: To determine how frequently SLN biopsy without completion lymph node dissection (CLND) results in long-term regional nodal disease control in patients with SLN metastases.

Design, setting, and participants: The second Multicenter Selective Lymphadenectomy Trial (MSLT-II), a prospective multicenter randomized clinical trial, randomized participants with SLN metastases to either CLND or nodal observation. The current analysis examines observation patients with regard to regional nodal recurrence. Trial patients were aged 18 to 75 years with melanoma metastatic to SLN(s). Data were collected from December 2004 to April 2019, and data were analyzed from July 2020 to January 2022.

Interventions: Nodal observation with ultrasonography rather than CLND.

Main outcomes and measures: In-basin nodal recurrence.

Results: Of 823 included patients, 479 (58.2%) were male, and the mean (SD) age was 52.8 (13.8) years. Among 855 observed basins, at 10 years, 80.2% (actuarial; 95% CI, 77-83) of basins were free of nodal recurrence. By univariable analysis, freedom from regional nodal recurrence was associated with age younger than 50 years (hazard ratio [HR], 0.49; 95% CI, 0.34-0.70; P < .001), nonulcerated melanoma (HR, 0.36; 95% CI, 0.36-0.49; P < .001), thinner primary melanoma (less than 1.5 mm; HR, 0.46; 95% CI, 0.27-0.78; P = .004), axillary basin (HR, 0.61; 95% CI, 0.44-0.86; P = .005), fewer positive SLNs (1 vs 3 or more; HR, 0.32; 95% CI, 0.14-0.75; P = .008), and SLN tumor burden (measured by diameter less than 1 mm [HR, 0.39; 95% CI, 0.26-0.60; P = .001] or less than 5% area [HR, 0.36; 95% CI, 0.24-0.54; P < .001]). By multivariable analysis, younger age (HR, 0.57; 95% CI, 0.39-0.84; P = .004), thinner primary melanoma (HR, 0.40; 95% CI, 0.22-0.70; P = .002), axillary basin (HR, 0.55; 95% CI, 0.31-0.96; P = .03), SLN metastasis diameter less than 1 mm (HR, 0.52; 95% CI, 0.33-0.81; P = .007), and area less than 5% (HR, 0.58; 95% CI, 0.38-0.88; P = .01) were associated with basin control. When looking at the identified risk factors of age (50 years or older), ulceration, Breslow thickness greater than 3.5 mm, nonaxillary basin, and tumor burden of maximum diameter of 1 mm or greater and/or metastasis area of 5% or greater and excluding missing value cases, basin disease-free rates at 5 years were 96% (95% CI, 88-100) for patients with 0 risk factors, 89% (95% CI, 82-96) for 1 risk factor, 86% (95% CI, 80-93) for 2 risk factors, 80% (95% CI, 71-89) for 3 risk factors, 61% (95% CI, 48-74) for 4 risk factors, and 54% (95% CI, 36-72) for 5 or 6 risk factors.

Conclusions and relevance: This randomized clinical trial was the largest prospective evaluation of long-term regional basin control in patients with melanoma who had nodal observation after removal of a positive SLN. SLN biopsy without CLND cleared disease in the affected nodal basin in most patients, even those with multiple risk factors for in-basin recurrence. In addition to its well-validated value in staging, SLN biopsy may also be regarded as therapeutic in some patients.

Trial registration: ClinicalTrials.gov Identifier: NCT00297895.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Thompson has received grants from the Australian National Health and Medical Research Council during the conduct of the study as well as personal fees from Bristol Myers Squibb, Merck Sharp & Dohme, GlaxoSmithKline, and Provectus and nonfinancial support from Novartis outside the submitted work. Dr Hyngstrom has received personal fees from Nektar/Bristol Myers Squibb outside the submitted work. Dr Zager has received personal fees for Castle Biosciences, Merck, Novartis, Philogen, and Delcath Systems outside the submitted work. Dr Bowles has received grants from Genentech and is principal investigator of clinical trials conducted by Genentech, Amgen, and Replimune outside the submitted work. Dr van Akkooi has received grants and personal fees from Amgen, Bristol Myers Squibb, Novartis, Merck Sharp & Dohme, Merck-Pfizer, Pierre Fabre, Sanofi, Sirius Medical, and 4SC paid to his institution outside the submitted work. Dr Dummer has received personal fees from Novartis, Merck Sharp & Dohme, Bristol Myers Squibb, Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome, Regeneron, Alligator, T3 Pharma, MaxiVAX SA, Pfizer, and touchIME outside the submitted work. Dr Neves reports personal fees from Novartis Advisory Board, personal fees from Castle Biosciences Advisory Board, and personal fees from Sanofi-Genzyme Advisory Board outside the submitted work. Dr Hsueh has received personal fees from Castle Biosciences outside the submitted work. Dr MacKenzie-Ross has received fees from John Wayne Cancer Institute paid to his institution during the conduct of the study. Dr Kelley has received fees from John Wayne Cancer Institute paid to his institution during the conduct of the study. Dr Terheyden has received personal fees from Bristol Myers Squibb, Novartis, Merck Sharp & Dohme, Pierre Fabre, CureVac, Merck Serono, Sanofi, Roche, Kyowa Kirin, Biofrontera, and Almirall outside the submitted work. Dr Gershenwald has received personal fees from Merck, Syndax, Regeneron, and Bristol Myers Squibb outside the submitted work. Dr Gesierich has received personal fees from Amgen, Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Pfizer, Roche, and Sanofi outside the submitted work. Dr Sardi has received grants from the John Wayne Cancer Institute during the conduct of the study. Dr Barth has received grants from the National Institutes of Health during the conduct of the study. Dr Slingluff has received grants from Celldex and Merck; nonfinancial support from Theraclion; personal fees from Curevac paid to his institution; and fees from Polynoma for serving as principal investigator of a multicenter trial paid to his institution; and has a patent for peptides for use in melanoma vaccines licensed. Dr Van Kreuningen has received grants from John Wayne Cancer Institute during the conduct of the study. Dr Scolyer has received grants from the National Health and Medical Research Council of Australia during the conduct of the study as well as personal fees from Qbiotics, Novartis, Merck Sharp & Dohme, NeraCare, Amgen, Bristol Myers Squibb, Myriad Genetics, and GlaxoSmithKline outside the submitted work. Dr Cochran has received grants from National Cancer Institute during the conduct of the study. Dr Faries has received grants from the National Institutes of Health during the conduct of the study as well as personal fees from Merck, Bristol Myers Squibb, Novartis, Array Bioscience, Sanofi, and Nektar outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. Sentinel Lymph Node (SLN) Basin Disease-Free Survival
A, Kaplan-Meier plot of nodal recurrence–free survival. B, Nodal recurrence–free survival among risk-stratified groups. + indicates censored patients.
See this image and copyright information in PMC

Comment in

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