The extent of surgery for stage III melanoma: how much is appropriate?

Abstract

Since the first documented lymph node dissection in 1892, many trials have investigated the potential effect of this surgical procedure on survival in patients with melanoma. Two randomised controlled trials were unable to demonstrate improved survival with completion lymph node dissection versus nodal observation in patients with sentinel node-positive disease, although patients with larger sentinel node metastases (>1 mm) might benefit more from observation than from dissection, and could potentially be considered for adjuvant systemic therapy instead of complete dissection. Adjuvant immunotherapy with high-dose ipilimumab has led to improvements in overall survival, whereas therapy with nivolumab and pembrolizumab has improved relapse-free survival with greater safety. Furthermore, adjuvant-targeted therapy with dabrafenib and trametinib has improved survival outcomes in BRAFV600E and BRAFV600K-mutated melanomas. Three neoadjuvant trials have all shown high response rates, including complete responses, after short-term combination therapy with ipilimumab and nivolumab with no recurrences so far, although follow-up is still short. Despite the absence of a survival benefit with completion lymph node dissection in patients with sentinel node-positive or negative disease, the use of sentinel node staging will increase because of the introduction of effective adjuvant therapies. However, routine completion lymph node dissection for sentinel node-positive disease should be reconsidered. Accordingly, existing clinical guidelines are currently being revised. For palpable (macroscopic) nodal disease, the type and extent of surgery could be reduced if the index node can accurately predict the response and if studies show that lymph node dissection can be safely foregone in patients with a complete response. Overall, the appropriate type and extent of surgery for stage III melanoma is changing and becoming more personalised.