Longitudinal ctDNA monitoring for post-surgical molecular residual disease in patients with stage I-IIIb melanoma.

Circulating tumor DNA (ctDNA) has emerged as an important biomarker for early recurrence detection and monitoring disease status in patients with cancer, including melanoma. Here, we evaluate the prognostic value and utility of post-operative ctDNA detection in patients with stage I-IIIb melanoma using a clinically validated, personalized, tumor-informed ctDNA assay. We conducted a retrospective analysis of real-world data of patients with stage I-IIIb melanoma (N=197), including ctDNA results using a personalized, tumor-informed, 16-plex mPCR-NGS assay (Signatera, Natera, Inc.). Adjuvant treatment decision and post-surgical plasma (N=1,718) sample collection during treatment for ctDNA analysis was at the provider’s discretion. ctDNA results were correlated with clinical outcomes. Across 197 patients analyzed for ctDNA, a median of 7 tests (range: 2-44) per patient were performed over a median period of 24.7 months (range: 3.7-74.7).ctDNA-positivity at any postoperative timepoint was significantly associated with shorter relapse-free survival (RFS; hazard ratio [HR]: 15.0, 95% CI: 7.3–31.0, < 0.0001). This finding was pronounced for patients with distant/regional recurrence (HR: 27.0, 95% CI: 10.0–71.0, < 0.0001). Multivariate analysis confirmed ctDNA-positivity to be the most significant prognostic factor associated with RFS when compared with other clinicopathologic factors such as adjuvant treatment, stage, sex, and mitotic rate (N=163, HR: 10.50, 95% CI: 3.891–28.32 < 0.001). Finally, we explored the utility of ctDNA-positivity and its impact on clinical decision-making and observed that ctDNA-positivity influenced changes in treatment management in 73.7% (N=28/38) of patients, ranging from imaging escalation to treatment initiation, switch, or escalation. Our findings highlight the prognostic value of post-surgical, personalized ctDNA detection and monitoring of molecular residual disease in stage I-IIIb melanoma and provide information on real-world clinical decision practices based on ctDNA changes.

Duke Scholars

Author Georgia Marie Beasley Surgical Oncology