Comparative genomics provides etiological and biological insights into melanoma subtypes

Newell F, Johansson PA, Wilmott JS, Nones K, Lakis V, Pritchard AL, Lo SN, Rawson RV, Kazakoff SH, Colebatch AJ, Koufariotis LT, Ferguson PM, Wood S, Leonard C, Law MH, Brooks KM, Broit N, Palmer JM, Couts KL, Vergara IA, Long GV, Barbour AP, Nieweg OE, Shivalingam B, Robinson WA, Stretch JR, Spillane AJ, Saw RPM, Shannon KF, Thompson JF, Mann GJ, Pearson JV, Scolyer RA, Waddell N, Hayward NK. Cancer Discov. 2022 Sep 13:CD-22-0603. doi: 10.1158/2159-8290.CD-22-0603. Epub ahead of print. PMID: 36098958.


Background: Metastasectomy for selected patients with melanoma was associated with improved survival in the era before effective systemic therapy. Emerging evidence shows that these benefits persist even in this era of BRAF-targeted therapy and immune checkpoint inhibitor immunotherapy. This study aimed to evaluate the outcomes of salvage metastasectomy after failure of systemic therapy.

Methods: Stage 3 or 4 melanoma patients with extracranial disease progression after at least 4 weeks of systemic treatment between 2009 and 2020 were identified and categorized as resected to no evidence of disease (NED), non-progressive residual disease (NPRD), or progressive residual disease (PRD). Systemic therapy was stratified into BRAF-targeted therapy, immune checkpoint inhibitor immunotherapy, or both. The end points of overall survival (OS), progression-free survival (PFS), and locoregional disease control (LRC) were assessed using Kaplan-Meier curves. Uni- and multivariable Cox regression procedures were used to examine factors associated with OS, PFS and LRC.

Results: The study enrolled 190 patients. Among all the patients, the 5-year OS from metastatectomy was 52%, the 3-year PFS was 21%, and the 5-year LRC was 61%. After resection to NED, NPRD, and PRD, the 5-year OS values were 69%, 62% and 8%, respectively. Fewer lines of preoperative therapy, use of preoperative immunotherapy, and resection to NED were predictors of improved OS. After resection to NED, NPRD, and PRD, the 3-year PFS values were 23%, 24% and 10%, and the 5-year LRC values were 61%, 72% and 34%, respectively.

Conclusions: Salvage metastasectomy was associated with durable survival and disease control, particularly after resection to NED, preoperative immunotherapy, and fewer lines of preoperative systemic therapy.