International Survey on Evidence for Index Lymph Node Surgery After Neoadjuvant Systemic Therapy for Stage III Melanoma.

Background: Neoadjuvant immunotherapy for resectable stage III melanoma has demonstrated promising outcomes in recent trials, prompting a change in clinical practice in many countries. Although therapeutic lymph node dissection (TLND) remains the standard of care after neoadjuvant treatment, a less invasive index lymph node (ILN)-guided approach has been proposed. The global melanoma community's acceptance of neoadjuvant immunotherapy and the need for TLND or ILN after this remains unclear.

Methods: A two-stage international survey was conducted among melanoma experts between May 2023 and January 2025. Respondents were asked about their familiarity with neoadjuvant trials, current practices, and opinions on ILN versus TLND before and after publication of the NADINA trial.

Results: The response rates were 50% (118/237) in the first survey and 62% (148/237) in the second survey. In the second survey, 74% of the respondents considered neoadjuvant therapy the standard of care, and support for ILN-guided surgery rose from 27 to 40% between the surveys. However, 54% still favored a phase 3 randomized controlled trial before changing the clinical practice guidelines, and only 27% believed the current data were sufficient for adoption of ILN as standard. Key barriers included concerns about oncologic safety, pathologic standardization, and patient selection.

Conclusion: The current evidence supports the use of neoadjuvant immunotherapy as the standard of care for stage III melanoma. However, widespread clinical adoption of ILN-guided surgical de-escalation remains limited. A multicenter phase 3 trial (MSLT-3), launching in 2025, is expected to provide important data to guide future practice.