TY - JOUR
T1 - Therapeutic Value of Sentinel Lymph Node Biopsy in Patients with Melanoma
T2 - A Randomized Clinical Trial
AU - Crystal, Jessica S.
AU - Thompson, John F.
AU - Hyngstrom, John
AU - Caracò, Corrado
AU - Zager, Jonathan S.
AU - Jahkola, Tiina
AU - Bowles, Tawnya L.
AU - Pennacchioli, Elisabetta
AU - Beitsch, Peter D.
AU - Hoekstra, Harald J.
AU - Moncrieff, Marc
AU - Ingvar, Christian
AU - Van Akkooi, Alexander
AU - Sabel, Michael S.
AU - Levine, Edward A.
AU - Agnese, Doreen
AU - Henderson, Michael
AU - Dummer, Reinhard
AU - Neves, Rogerio I.
AU - Rossi, Carlo Riccardo
AU - Kane, John M.
AU - Trocha, Steven
AU - Wright, Frances
AU - Byrd, David R.
AU - Matter, Maurice
AU - Hsueh, Eddy C.
AU - Mackenzie-Ross, Alastair
AU - Kelley, Mark
AU - Terheyden, Patrick
AU - Huston, Tara L.
AU - Wayne, Jeffrey D.
AU - Neuman, Heather
AU - Smithers, B. Mark
AU - Ariyan, Charlotte E.
AU - Desai, Darius
AU - Gershenwald, Jeffrey E.
AU - Schneebaum, Shlomo
AU - Gesierich, Anja
AU - Jacobs, Lisa K.
AU - Lewis, James M.
AU - McMasters, Kelly M.
AU - O'Donoghue, Cristina
AU - Van Der Westhuizen, Andre
AU - Sardi, Armando
AU - Barth, Richard
AU - Barone, Robert
AU - McKinnon, J. Greg
AU - Slingluff, Craig L.
AU - Farma, Jeffrey M.
AU - Schultz, Erwin
AU - Scheri, Randall P.
AU - Vidal-Sicart, Sergi
AU - Molina, Manuel
AU - Testori, Alessandro A.E.
AU - Foshag, Leland J.
AU - Van Kreuningen, Lisa
AU - Wang, He Jing
AU - Sim, Myung Shin
AU - Scolyer, Richard A.
AU - Elashoff, David E.
AU - Cochran, Alistair J.
AU - Faries, Mark B.
N1 - Publisher Copyright:
© 2022 American Medical Association. All rights reserved.
PY - 2022/9
Y1 - 2022/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85135892974&partnerID=8YFLogxK
U2 - 10.1001/jamasurg.2022.2055
DO - 10.1001/jamasurg.2022.2055
M3 - Article
C2 - 35921122
AN - SCOPUS:85135892974
SN - 2168-6254
VL - 157
SP - 835
EP - 842
JO - JAMA Surgery
JF - JAMA Surgery
IS - 9
ER -