Circulating Tumor DNA Predicts Response After Definitive Radiation Therapy for Merkel Cell Carcinoma

Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer with a high recurrence rate. Circulating tumor DNA (ctDNA) assays are increasingly used to assess treatment response and detect recurrence. This study evaluated the value of ctDNA levels in MCC patients treated with definitive radiation therapy (dRT).

We identified 48 patients with MCC treated with dRT from 2021-2024 treated at our institute. The level of ctDNA was measured within 90 days before and 180 days after initiating dRT using a tumor-informed multiplex polymerase chain reaction assay targeting up to 16 patient-specific mutations. Disease status at follow-up was categorized as no evidence of disease (NED) or clinical evidence of disease. ctDNA dynamics were compared across disease outcome groups using the Wilcoxon rank-sum test.

At baseline, the value of median ctDNA levels were higher in stage 1 versus stage 1-2. Of 23 patients with detectable ctDNA levels at baseline, 15 achieved undetectable levels following dRT. ctDNA levels declined significantly during (P = .0125) and after dRT (P = .0004). Among patients who became NED, ctDNA levels declined rapidly. In contrast, persistent or rising value of ctDNA levels after dRT was associated with recurrence. Nine of 10 patients with detectable ctDNA levels after dRT experienced recurrence, with a median time to recurrence of 117 days. Among patients with undetectable ctDNA levels during dRT, the negative predictive value for recurrence was 90%.

ctDNA levels decline rapidly during and after dRT in patients with MCC, particularly in those who achieve NED. Detectable ctDNA levels after dRT are strongly associated with recurrence, supporting the use of ctDNA level as a noninvasive biomarker to assess treatment response and guide posttreatment surveillance.