Impact of Effective Systemic Therapy on Metastasectomy in Stage IV Melanoma: A Matched-Pair Analysis

Although resection historically played a prominent role in the treatment of metastatic melanoma, recent advances have altered the therapeutic landscape, and potentially the role of surgery. We examined surgical selection and metastasectomy outcomes before and after the onset of the effective drug therapy era.

Patients with stage IV melanoma were identified and characterized by treatment era (either 1965-2007 or 2008-2015) and by systemic therapy agents. BRAF and/or MEK inhibitors, as well as checkpoint inhibitors, were included as modern agents. Selection factors for metastasectomy were examined by era. A matched-pair analysis of outcomes of surgical and non-surgical patients receiving modern systemic agents was performed.

Among 2353 eligible patients, 1065 (45.2%) underwent surgical treatment. Factors associated with selection for metastasectomy in the early era included female sex, no prior stage III disease, single-organ involvement, and M1a (vs. M1c) disease (all p < 0.007). In the current era, the proportion of surgically treated patients increased modestly (54.5% vs. 44.7%, p = 0.02) and age was the only independent selection factor (p < 0.01). Surgery followed by modern therapy in 47 matched pairs was associated with higher 5-year melanoma-specific survival (MSS) versus modern therapy alone (58.8% vs. 38.9%, p = 0.049). Multivariable regression showed single-organ involvement (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.21-0.90, p = 0.02) and first-line surgery (HR 0.47, 95% CI 0.23-0.98, p = 0.04), as well as use of modern agents (HR 0.29, 95% CI 0.21-0.40, p < 0.001), were independently associated with improved MSS.

While modern systemic agents have improved outcomes in stage IV melanoma, metastasectomy remains associated with favorable survival. Resection remains a viable therapeutic approach, possibly worthy of prospective evaluation.