The impact of effective systemic therapies on surgery for stage IV melanoma

Abstract

Introduction: The outcomes of patients with metastatic melanoma have significantly improved with the introduction of effective systemic therapies (ESTs). The role of surgery in the context of ESTs for stage IV melanoma is evolving. We sought to characterise the changing patterns of surgery and oncological outcomes in patients with stage IV melanoma treated before and after the establishment of ESTs.

Methods: Patients undergoing surgical resection of stage IV melanoma were identified from our institutional database from 2003 to 2015. Patients were grouped into two cohorts, those referred before EST (2003-2007) and after EST (2011-2015). Clinicopathological variables, patterns of surgery and oncological outcomes in the two groups were compared.

Results: A total of 138 patients underwent surgery for stage IV melanoma (n = 69 in each cohort). We observed no significant difference in the ratio of operations/patients performed. However, the pattern of operations altered, with a significant decrease in in-transit excisions (0.9% vs. 19.4%, p < 0.001) and an increase in abdominal metastasectomies (21.1% vs. 4.2%, p < 0.001), in the after-EST cohort. Novel indications for surgical intervention were noted in the after-EST cohort, with a significant increase in potentially curative operations for residual oligometastatic disease (15.9% vs. 4.3%, p = 0.045). Survival after surgery was prolonged in the after-EST cohort (median 16 months vs. 6 months, p < 0.001), with the stage at initial metastasectomy (stage 4a, hazard ratio [HR] 0.45 (0.28-0.73), p = 0.001) and treatment with immune checkpoint inhibitors (HR 0.38 (0.25-0.60), p < 0.001) associated with prolonged survival.

Discussion: Surgery remains important in the management of stage IV melanoma, with evolving indications and patterns of intervention after the introduction of ESTs. The combination of judicious surgery and EST may improve oncological outcomes.

Keywords: Immunotherapy; Metastasectomy; Stage IV melanoma; Surgery.