The Role of ctDNA in the Diagnosis and Management of Metastatic Melanoma

In the final segment of this discussion, the panel explores the evolving role of ctDNA in managing metastatic melanoma. Although ctDNA is not yet a formal part of standard care, its clinical utility is gaining interest, especially as an MRD marker or diagnostic adjunct when tissue biopsies are difficult. One panelist notes limited but thoughtful use in clinical scenarios where imaging is inconclusive or biopsy is impractical. Although the idea of using ctDNA to guide the duration of immunotherapy is promising, evidence supporting this practice is still lacking.

At more research-focused centers, ctDNA testing is being implemented more routinely, even though it remains unapproved by the FDA and is often unreimbursed. For example, one institution collects ctDNA for most patients with stage IIB or higher melanoma, using platforms such as Natera’s genomic assay to monitor tumor dynamics. However, this use remains in the research realm, with the data helping inform trends rather than driving clinical decisions. Another panelist highlights a growing trend among community oncologists to integrate ctDNA testing into treatment monitoring, although caution is advised regarding its interpretation.

The panel collectively agrees that although ctDNA shows potential, its limitations must be clearly understood. An undetectable ctDNA result does not definitively mean the absence of disease—it may reflect assay sensitivity, low tumor burden, or biological factors such as tumor shedding. As the field advances, ctDNA could become a valuable biomarker, but for now, it remains largely investigational. The consensus is that gathering real-world data is essential to establishing its predictive value and role in outcome improvement, with hopes that ongoing research will clarify how best to integrate ctDNA into melanoma management.