The Landmark Series: Neoadjuvant Systemic Therapy (NAST) for Stage 3 Melanoma Patients - A Potential Paradigm Shift...

Area of Science:

• Oncology
• Immunotherapy
• Dermatology

Background:

• Systemic therapies have transformed melanoma management for stages 3 and 4.
• Neoadjuvant therapies are emerging as a novel strategy for high-risk stage 3 melanoma.

Purpose of the Study:

• To evaluate the efficacy and predictive value of neoadjuvant immune checkpoint blockade (ICB) and targeted therapies in advanced melanoma.
• To explore the potential for reducing lymph node dissection and adjuvant therapy in patients achieving complete pathologic response.

Main Methods:

• Review of neoadjuvant treatment strategies including ICB and targeted therapies (dabrafenib plus trametinib).
• Analysis of patient responses, focusing on pathologic complete response (pCR) and near-pCR.
• Assessment of treatment-related toxicities and their impact on quality of life.

Main Results:

• Neoadjuvant ICB responders demonstrate an excellent prognosis, with pCR or near-pCR being strong predictors of improved outcomes.
• Neoadjuvant targeted therapy (dabrafenib plus trametinib) generally yields clinical and pathologic responses, but pCR is less predictive than with ICB.
• Treatment-related toxicities are currently manageable but can affect quality of life.

Conclusions:

• Neoadjuvant ICB is a promising approach for stage 3 melanoma, offering survival benefits.
• Pathologic complete response after neoadjuvant ICB is a reliable indicator of favorable prognosis.
• Further research, ideally coordinated through the International Neoadjuvant Melanoma Consortium, is needed to optimize neoadjuvant treatment strategies and minimize patient burden.