Longitudinal ctDNA monitoring for post-surgical disease surveillance in patients with stage I-IIIB melanoma

Abstract Purpose: Circulating tumor DNA (ctDNA) has emerged as an important biomarker for early recurrence detection and monitoring disease status during treatment in patients with cancer, including melanoma. We evaluate the prognostic value and impact of post-operative ctDNA detection in patients with stage I-IIIB melanoma using a clinically validated ctDNA assay. Experimental Design: We conducted a retrospective analysis of real-world data of patients with stage I-IIIB melanoma, including ctDNA results using a personalized, tumor-informed, 16-plex mPCR-NGS assay. Adjuvant treatment decisions and post-surgical plasma sample collection timepoints were at the physician’s discretion. ctDNA results were correlated with clinical outcomes. Results: Across 190 patients and a total of 1,578 samples, a median of 7 ctDNA tests (range: 1–33) per patient were performed over a median period of 24.6 months (range: 3.7 – 74.7). ctDNA-positivity at any postoperative timepoint was significantly associated with shorter recurrence-free survival (RFS; hazard ratio HR: 40.63, 95% CI: 19.9 – 82.96, P0.0001). This finding was also observed in patients specifically with regional or distant recurrence (HR: 39.55, 95% CI: 18.08 – 86.51, P0.0001). In multivariate analysis, ctDNA-positivity was the most significant prognostic factor associated with RFS when compared with other clinicopathologic factors, including stage, sex, and mitotic rate (HR: 25.36, 95% CI: 9.16–70.3, P0.001). Conclusions: Our findings highlight the prognostic value of post-surgical, personalized ctDNA detection of recurrence and longitudinal disease surveillance in stage I-IIIB melanoma. The impact of ctDNA on real-world clinical decision-making highlights the need to assess outcomes when cancer management is influenced by ctDNA dynamics.