Sentinel lymph node biopsy in melanoma: Redundant in the neoadjuvant era.

BACKGROUND: Neoadjuvant immunotherapy has emerged as a superior strategy to adjuvant immunotherapy for patients with resectable, clinically detectable stage III melanoma, significantly improving event-free survival. In microscopic stage III disease, adjuvant immunotherapy is generally considered standard of care, although lack of survival benefit prompts re-evaluation of this sentinel lymph node biopsy (SLND) plus adjuvant therapy approach. Specifically, omission of SLNB may not only spare patients from surgery but also facilitate more effective systemic therapy, reduce the required number of immunotherapy doses, and potentially improve long-term oncological outcomes. METHODS: Data from pivotal melanoma immunotherapy trials and MSLT-1 trail were used to model two clinical scenarios: (1) SLNB followed by adjuvant immunotherapy in patients with a positive sentinel lymph node, and (2) omission of SLNB and clinical observation. A subsequent nodal recurrence then treated using neoadjuvant anti-PD-1 plus anti-CTLA-4 immunotherapy. Distant metastasis-free survival (DMFS) was simulated using a Markov model. FINDINGS: Omission of SLNB with treatment of nodal recurrence using neoadjuvant combination immunotherapy resulted in a 8-19 percentage point improvement in DMFS compared with the SLNB strategy followed by adjuvant immunotherapy in patients with a positive sentinel lymph node. The magnitude of benefit varied according to Breslow thickness. INTERPRETATION: Omitting SLNB may improve oncological outcomes in patients with melanoma in the era of neoadjuvant immunotherapy. These findings provide a compelling rationale for an international randomized controlled trial to re-evaluate the role of SLNB within contemporary melanoma treatments.