Evolving Applications of Circulating Tumor DNA in Merkel Cell Carcinoma

SIMPLE SUMMARY: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine cutaneous malignancy that is well-suited for liquid biopsy due to high levels of tumor DNA shedding into the bloodstream. An increasing number of studies have illustrated potential applications of circulating tumor DNA (ctDNA) in the management of patients with MCC. Here we describe the evolving applications of ctDNA in MCC, from quantifying tumor burden, to monitoring for early recurrence, detecting minimal residual disease, and predicting treatment response. ABSTRACT: Circulating tumor DNA (ctDNA) is a subset of circulating cell-free DNA released by lysed tumor cells that can be characterized by its shorter strand length and tumor genome-specific information. The relatively short half-life of ctDNA allows it to provide a real-time measure of tumor burden which has potential prognostic and surveillance value as a tumor biomarker. Merkel cell carcinoma (MCC) is a rare neuroendocrine skin cancer that requires close monitoring due to the high risk of relapse. There are currently no good tumor biomarkers for MCC patients, especially those who are negative for Merkel cell polyomavirus. ctDNA shows promise for improving the prognoses of MCC patients by monitoring tumor burden, identifying minimal residual disease (MRD), and stratifying patients by their likelihood of response to immune checkpoint inhibition or risk of relapse. In particular, bespoke ultra-sequencing platforms allow for the creation of patient-specific mutation panels that improve ctDNA detection, especially for patients with rare or uncharacteristic mutations. Leveraging bespoke ctDNA assays may improve physicians’ ability to alter treatment plans for non-responsive or high-risk patients. In addition, ctDNA MRD monitoring may allow physicians to treat relapses early before clinically evident disease is present.