Surgery for Unresectable Stage IIIC and IV Melanoma in the Era of New Systemic Therapy

Abstract

Opportunities for surgical treatment in metastatic melanoma patients have re-emerged due to the development of novel systemic therapeutics over the past decade. The aim of this study is to present data on outcomes of surgery in patients with unresectable stage IIIC and IV melanoma, who have previously been treated with immunotherapy or targeted therapy. Data was extracted from the Dutch Melanoma Treatment Registry (DMTR) on 154 patients obtaining disease control to systemic therapy and undergoing subsequent surgery. Disease control was defined as a complete response (CR), which was seen in 3.2% of patients; a partial response (PR), seen in 46.1% of patients; or stable disease (SD), seen in 44.2% of patients. At a median follow-up of 10.0 months (interquartile range 4–22) after surgery, the median overall survival (OS) had not been reached in our cohort and median progression-free survival (PFS) was 9.0 months (95% CI 6.3–11.7). A CR or PR at first follow-up after surgery was associated with both a better OS and PFS compared to stable or progressive disease (p < 0.001). We conclude that selected patients can benefit from surgery after achieving disease control with systemic therapy.

Age-Based Disparities in Metastatic Melanoma Patients Treated in the Immune Checkpoint Inhibitors (ICI) Versus Non-ICI Era: A Population-Based Study

“…This finding holds when the disease progression pattern during ICI treatment regards a few sites, which can be surgically approached or tackled with radiotherapy, resulting in one interpretation of the correlative analysis. Previous studies reported favorable survival when distant melanoma tissues were removed via surgery after checkpoint blockade, especially when they responded to ICI treatment ( 22 , 23 ). Administration of chemotherapy was highly observed in patients in the non-ICI era, mostly because it was the only treatment modality available.…”

Genetic Variants in Immune Related Genes as Predictors of Responsiveness to BCG Immunotherapy in Metastatic Melanoma Patients

“…Adjuvant immunotherapies that have been used in melanoma clinical trials are: Interferon-α-2b (IFN-α-2b), Interleukin (IL)-2, melanoma cell vaccines, BCG (Bacillus Calmette-Guérin), and immune checkpoint inhibitors (ICI) immunotherapy in post-surgical, disease-free AJCC (American Joint Committee on Cancer) stage III and IV patients [ 1 , 2 , 3 , 4 ]. Newer immunotherapies using monoclonal antibodies, such as ICIs, which target against CTLA-4, PD-1, or PD-L1 [ 5 , 6 , 7 ], have improved overall survival time when used as both adjuvant and neo-adjuvant therapies in AJCC stage III/IV melanoma patients [ 8 , 9 , 10 , 11 ]. ICI agents, nivolumab and pembrolizumab therapies, which are less toxic and have better recurrence-free survival rates, are the most effective and current standard of care for the treatment of melanoma patients [ 1 ].…”