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- Presentation
Neoadjuvant Therapy for High-Risk Melanoma: Pathologic Response, De-escalation, and Evolving Standards of Care
Description
The speaker reviews the evolution of neoadjuvant therapy for high-risk melanoma, especially resectable stage III disease, and emphasizes that accurate pathologic response assessment is central to guiding treatment decisions. He explains the shift from traditional adjuvant therapy to neoadjuvant or perioperative approaches, highlighting the biologic rationale that preoperative treatment exposes the immune system to intact tumor antigens and may improve recurrence-free survival. A major focus is the work of the International Neoadjuvant Melanoma Consortium to standardize pathology reporting by measuring percent residual viable tumor in treated tumor beds and classifying responses as complete, near-complete, partial, or non-response. Pooled analyses showed that pathologic response strongly correlates with recurrence-free survival, with important differences between targeted therapy and immune checkpoint therapy: BRAF-targeted therapy appears to require a complete pathologic response for meaningful benefit, whereas immunotherapy benefits extend across response categories except in non-responders. Large trials such as SWOG 1801 and NADINA established neoadjuvant therapy as a new standard of care, and newer studies are using pathologic response to de-escalate adjuvant therapy. The talk also describes surgical de-escalation strategies, including index-node-only approaches and the planned MSLT3 trial, which may spare patients full lymphadenectomy and its morbidity if they achieve major pathologic response. Looking ahead, the speaker notes expanding neoadjuvant use in high-risk primary melanomas, promising results in desmoplastic melanoma, and the growing role of circulating tumor DNA and other biomarkers to monitor response. The field is presented as a collaborative effort that has materially changed melanoma care.
View moreConclusions
- Neoadjuvant therapy has become a superior and now standard approach for resectable high-risk stage III melanoma because it improves event-free and recurrence-free survival compared with adjuvant-only treatment.
- Pathologic response after neoadjuvant therapy is a clinically valuable biomarker that strongly predicts patient outcomes and should guide post-operative management.
- Standardized, harmonized pathologic assessment is essential because neoadjuvant-treated tumors show mixed, geographically distributed treatment effects that require a different reporting framework than conventional lymphadenectomy specimens.
- The percent residual viable tumor can be reproducibly categorized into complete, near-complete, partial, and non-response groups, enabling meaningful comparison across trials.
- Pooled data from multiple neoadjuvant melanoma trials show that better pathologic response correlates with better recurrence-free survival.
- The prognostic meaning of response differs by treatment type: for targeted therapy, only complete pathologic response appears sufficient, whereas immune checkpoint therapy shows outcome benefit across the broader response spectrum.
- Trials such as SWOG 1801 and NADINA demonstrate that neoadjuvant immunotherapy improves outcomes and support response-adapted treatment decisions after surgery.
- Assessing the index lymph node alone can often approximate the pathology of the whole nodal basin, supporting safe surgical de-escalation in selected responders.
- Response-directed surgery can spare some patients completion lymphadenectomy and adjuvant therapy without compromising favorable outcomes when a major pathologic response is achieved.
- Future melanoma care is likely to expand neoadjuvant strategies to high-risk primary disease and other skin cancers, while incorporating ctDNA and imaging as complementary response-monitoring tools.
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