Plasma total cell-free DNA (cfDNA) is a surrogate biomarker for tumour burden and a prognostic biomarker for survival in metastatic melanoma patients.

•A prospective biomarker cohort study for total circulating cell-free DNA (cfDNA) in plasma was performed in metastatic melanoma patients. Paired blood collections and scan assessments were studied. CfDNA was measured by means of droplet digital Polymerase Chain Reaction and tumour burden was calculated as the sum of volumes from three-dimensional radiological measurements of all metastatic lesions in individual patients.•Baseline plasma cfDNA level correlates to tumour volume.•Plasma cfDNA level and is a surrogate biomarker for tumour burden and tumour burden changes after treatment.•Plasma cfDNA level is a prognostic marker for survival in metastatic melanoma patients.