The Surgeons’ Role When Systemic Therapies Fail in Metastatic Melanoma: The Salvage Metastasectomy

Abstract

The past decade has seen a tremendous improvement in the advent of newer, much more effective, and less toxic systemic therapies for melanoma including immunotherapies such as CTLA-4, and anti-PD-1 inhibitors as well as targeted therapies (BRAF and MEK inhibition). How many times have we heard that phrase? There are numerous published articles and podium talks where we start out with the same statement or a close version of it. But what do we do when these new, powerful, and effective therapies fail? The current article in this issue of Annals of Surgical Oncology by Li, Ch’ng, and colleagues attempts to answer this therapeutic challenge in a patient with metastatic melanoma. There have been numerous articles published on the surgeons’ instrumental role in the management of patients with advanced melanoma, how resection of progressive and isolated disease has led to improved survival in select patients, and how a multidisciplinary team approach combining systemic therapies (systemic, adjuvant, or neoadjuvant) with surgery has many advantages in terms of prolonging survival. Nelson et al. looked at patients with stage IV melanoma and characterized them by treatment era (prior to 2007 and 2007–2015). In their paper, they discuss a matched-pair analysis of outcomes in surgical and nonsurgical patients receiving modern-day systemic therapies for metastatic melanoma. Among over 2000 patients analyzed, just under half underwent surgical treatment, with the only independent selection factor associated with surgical metastectomy in the current era (2007–2015) being age of the patient. Surgery followed by modern therapy in 47 matched pairs was associated with higher melanoma-specific survival (MSS), with single-organ involvement (p = 0.02), first-line surgery (p = 0.04), and use of modern-day systemic therapies (p \\ 0.001) independently associated with improved MSS on multivariate analysis when compared with older-era patients with stage IV disease. This clearly shows that the multidisciplinary approach of combining systemic therapies with upfront surgery for stage IV disease in selected patients leads to better outcomes. In that same issue of Annals of Surgical Oncology, Song and colleagues also discussed a retrospective analysis looking at patients with clinical stage III melanoma and came to a similar conclusion looking at over 3700 patients; those treated in the modern era for their clinically evident metastatic stage III melanoma followed by modern-day adjuvant therapy did better in terms of overall survival (OS). These two papers clearly show that, in selected patients, surgery followed by modern-day systemic therapies can lead to improved survival. But what do we do when we treat patients with upfront systemic immunoor targeted therapies, and they fail or progress? It is apparent that we will be presented with these types of patients more commonly, as systemic therapies are obviously not 100% effective. Bello et al. previously described favorable survival outcomes after metastasectomy for isolated progressive disease in patients with prior checkpoint blockade. The current article’s authors, Li, Ch’ng, and colleagues, further attempt to characterize the outcomes of 190 patients who failed systemic therapy for extracranial metastatic disease (2009–2020) and then went on to have salvage surgery/ Society of Surgical Oncology 2021