Melanoma surgery in the era of modern immunotherapy

Abstract

Recent advances in immuno-oncology have led to a paradigm shift in the treatment of advanced cutaneous melanoma. The aim of this thesis is to investigate the role of surgery in the management of melanoma in this modern era of effective systemic treatments. This is done using a comprehensive approach of both retrospective and prospective study designs. In Paper I, we gathered international data from a large number of melanoma centers to examine the efficacy of immunotherapy on melanoma in-transit metastases and found immunotherapy to be effective in this patient group. In Paper II, we investigated the effect of isolated limb perfusion in patients that had received previous systemic immunotherapy and found it remains an effective treatment option. In Paper III, we used data from the Swedish national melanoma registry to show the prognostic value of sentinel lymph node status also in thick (>4.0 mm) melanomas, and our study supports a recommendation for sentinel lymph node biopsy also for thick tumors. In Paper IV, we performed a randomized controlled trial investigating the safety and preliminary efficacy of a single dose of the PD-1 inhibitor nivolumab prior to isolated limb perfusion for in-transit metastases, and found it to be safe and with promising efficacy. This thesis shows a strong continued role for surgery and locoregional treatments for patients with advanced melanoma, and underscores the evolving and dynamic nature of melanoma management, where a multidimensional approach holds the key to optimizing patient outcomes.