Kristy Kummerow Broman1,2, Tasha Hughes3, Lesly Dossett3, James Sun1, Dennis Kirichenko2, Michael J Carr1, Avinash Sharma4, Edmund K Bartlett4, Amanda A G Nijhuis5, John F Thompson5, Tina J Hieken6, Lisa Kottschade6, Jennifer Downs7, David E Gyorki7, Emma Stahlie8, Alexander van Akkooi8, David W Ollila9, Jill Frank9, Yun Song10, Giorgos Karakousis10, Marc Moncrieff11, Jenny Nobes11, John Vetto12, Dale Han12, Jeffrey M Farma13, Jeremiah L Deneve14, Martin D Fleming14, Matthew C Perez15, Michael C Lowe15, Roger Olofsson Bagge16, Jan Mattsson16, Ann Y Lee17, Russell S Berman17, Harvey Chai18, Hidde M Kroon18, Juri Teras19, Roland M Teras19, Norma E Farrow20, Georgia Beasley20, Jane Yuet Ching Hui21, Lukas Been22, Schelto Kruijff22, Youngchul Kim1, Syeda Mahrukh Hussnain Naqvi1, Amod A Sarnaik1,2, Vernon K Sondak1,2, Jonathan S Zager1,2. 1. Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida. 2. Department of Oncologic Sciences, University of South Florida Morsani School of Medicine, Tampa, Florida. 3. Department of Surgery, University of Michigan, Ann Arbor, Michigan. 4. Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York. 5. Department of Surgery, Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia. 6. Department of Surgery, Department of Oncology, Mayo Clinic, Rochester, Minnesota. 7. Division of Cancer Surgery, Peter MacCallum Cancer Center, Melbourne, Australia. 8. Division of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands. 9. Department of Surgery, University of North Carolina, Chapel Hill, North Carolina. 10. Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania. 11. Department of Plastic Surgery, Norfolk and Norwich University Hospital, Norwich, United Kingdom. 12. Department of Surgery, Oregon Health & Science University, Portland, Oregon. 13. Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania. 14. Department of Surgery, University of Tennessee, Memphis, Tennessee. 15. Department of Surgery, Emory University, Atlanta, Georgia. 16. Department of Surgery, Sahlgrenska Center for Cancer Research, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. 17. Department of Surgery, NYU Langone Health, New York, New York. 18. Discipline of Surgery, Faculty of Health and Medical Sciences, School of Medicine, University of Adelaide, Royal Adelaide Hospital, Adelaide, Australia. 19. Surgery Clinic, North Estonia Medical Center Foundation, Tallinn, Estonia. 20. Department of Surgery, Duke University, Durham, North Carolina. 21. Department of Surgery, University of Minnesota, Minneapolis, Minnesota. 22. Department of Surgical Oncology, University Medical Center, Groningen, the Netherlands.
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.
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.
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