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)

Kristy Kummerow Broman, Tasha Hughes, Lesly Dossett, James Sun, Dennis Kirichenko, Michael J. Carr, Avinash Sharma, Edmund K. Bartlett, Amanda A.G. Nijhuis, John F. Thompson, Tina J. Hieken, Lisa Kottschade, Jennifer Downs, David E. Gyorki, Emma Stahlie, Alexander van Akkooi, David W. Ollila, Jill Frank, Yun Song, Giorgos KarakousisMarc Moncrieff, Jenny Nobes, John Vetto, Dale Han, Jeffrey M. Farma, Jeremiah L. Deneve, Martin D. Fleming, Matthew C. Perez, Michael C. Lowe, Roger Olofsson Bagge, Jan Mattsson, Ann Y. Lee, Russell S. Berman, Harvey Chai, Hidde M. Kroon, Juri Teras, Roland M. Teras, Norma E. Farrow, Georgia Beasley, Jane Yuet Ching Hui, Lukas Been, Schelto Kruijff, Youngchul Kim, Syeda Mahrukh Hussnain Naqvi, Amod A. Sarnaik, Vernon K. Sondak, Jonathan S. Zager

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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.

Original languageEnglish (US)
Number of pages11
JournalCancer
Volume127
Issue number13
Early online dateApr 7 2021
DOIs
StateE-pub ahead of print - Apr 7 2021

Bibliographical note

Funding Information:
John F. Thompson reports personal fees from Bristol‐Meyers Squibb Australia and Merck Sharp & Dohme Australia and personal fees and travel support from GlaxoSmithKline and Provectus Inc, outside the submitted work. Tina J. Hieken reports grants from Genentech, outside the submitted work. David E. Gyorki reports personal fees from Amgen, outside the submitted work. Alexander van Akkooi reports grants and personal fees from Amgen, Bristol‐Myers Squibb, and Novartis; and personal fees from 4SC, Merck‐Pfizer, MSD‐Merck, and Sanofi, outside the submitted work. Jeffrey M. Farma reports personal fees from Novartis and Delcath, outside the submitted work. Roger Olofsson Bagge reports grants from Astra Zeneca and personal fees from Amgen, BD/Bard, Bristol‐Myers Squibb, Merck Sharp & Dohme, Novartis, Roche, and Sanofi Genzyme, outside the submitted work. Georgia Beasley reports grants form Istari Oncology and personal fees from Sanofi‐Regeneron, outside the submitted work. Amod A. Sarnaik reports grants from Provectus Inc and grants and personal fees from Iovance Biotherapeutics, outside the submitted work. Vernon K. Sondak reports personal fees from Array, Bristol‐Myers Squibb, Genentech/Roche, Merck, Novartis, Regeneron, Replimune, Pfizer, and Polynoma, outside the submitted work. Jonathan S. Zager reports grants from Amgen, Delcath Systems, Philogen, and Provectus; grants and personal fees from Castle Biosciences and Novartis, and personal fees from Array Biopharma, Merck, and Sun Pharma, outside the submitted work. The remaining authors made no disclosures.

Funding Information:
This work was supported in part by the Biostatistics and Bioinformatics Shared Resource at the H. Lee Moffitt Cancer Center and Research Institute, a National Cancer Institute‐designated comprehensive cancer center (P30‐CA076292).

Publisher Copyright:
© 2021 American Cancer Society

Keywords

  • active surveillance
  • cohort studies
  • cutaneous malignant melanoma
  • follow-up studies
  • immunotherapy
  • lymph node excision
  • metastatic melanoma
  • sentinel lymph node

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