Circulating Tumor DNA in High-Risk Stage II/III Cutaneous Melanoma: A Feasibility Study.

Abstract

Background: Adjuvant therapies reduce recurrence in patients with clinical stage IIB/IIC/III melanoma; however, better risk stratification and patient selection are needed. Circulating tumor DNA (ctDNA) as a marker of micrometastatic residual disease is being explored for such purposes in other malignancies. We aimed to explore the feasibility of serial ctDNA monitoring in patients with stage II/III melanoma, as well as the association of ctDNA elevation with disease burden and outcomes.

Methods: A single-institution prospective study was conducted on patients with clinical stage IIB/IIC/III melanoma. Primary tumor was sent to Natera for generation of a tumor-informed mPCR-NGS assay (Signatera™). Peripheral blood was collected for analysis at pre-specified timepoints. Patients were stratified by ctDNA elevations both pre- and postoperatively to compare tumor characteristics and recurrence-free survival (RFS).

Results: Overall, 30 patients were enrolled. The median Breslow depth was 4.4 mm and 70% were ulcerated. Signatera™ assays were successfully created for all 30 patients. Median follow-up from the time of surgery was 16 months and 13 patients recurred with median RFS of 19 months. Eight of these 13 patients (62%) had detectable ctDNA levels predating their clinical or radiographic recurrence. Elevated ctDNA at the first post-operative timepoint was associated with worse RFS.

Conclusions: ctDNA monitoring is feasible for patients with high-risk cutaneous melanoma. Our findings suggest that detectable ctDNA post-operatively may be associated with worse outcomes. Elevations during surveillance may predict subsequent clinical recurrence; however, the role of ctDNA in adjuvant therapy decision-making and surveillance is not yet ready for broad application.