Circulating tumor DNA level is associated with time to clinical recurrence in Merkel cell carcinoma: Implications for patient management
October 10, 2025
Journal
Journal of the American Academy of Dermatology
Publication Date
October 10, 2025
Authors
Merkelcell.org Summary
Merkel cell carcinoma (MCC) is a rare skin cancer that often comes back after treatment, which is called recurrence. This study looked at a blood test called circulating tumor DNA (ctDNA) to see if it could help detect MCC recurrence earlier. Tumor cells shed small, harmless pieces of DNA into the bloodstream. ctDNA is a blood test that measures the amount of DNA from the MCC tumor that was released into the blood.
Researchers followed 215 MCC patients who had finished their initial MCC treatment and performed 669 ctDNA tests across these patients. They found that about 77% of patients with positive ctDNA developed visible signs of cancer within a year. In fact, on average, ctDNA detected recurrence about 2.7 months before it could be seen on imaging scans.
The researchers also noticed that higher ctDNA levels meant the cancer was likely to return sooner: usually within 3 months for high levels, within 6 months for medium levels, and within 9 months for low levels. Because this was a real-world study, there were some differences in how often patients had scans or ctDNA tests, but overall the results were consistent.
This suggests that ctDNA testing could help doctors find MCC recurrences earlier and personalize MCC care. For example, patients with negative ctDNA tests might not need scans as often, while those with positive results could be monitored more closely or treated sooner. If you are a patient with MCC, consider talking to your healthcare team about whether ctDNA could be a good option for tracking your cancer.
Abstract
Background: Merkel cell carcinoma (MCC) recurs in 40% of patients. Circulating tumor DNA (ctDNA) is an emerging blood-based biomarker for early MCC recurrence detection.
Objective: To evaluate the timing and prognostic significance of ctDNA levels relative to clinical recurrence.
Methods: This multicenter prospective study analyzed 669 tumor-informed ctDNA tests from 215 MCC patients (stage I-IV) without clinically evident disease after treatment.
Results: Patients with at least one positive ctDNA test were more likely to experience recurrence compared to ctDNA-negative patients (hazard ratio: 18.1, 95% CI: 8.9-36.7), with 77% developing clinically evident disease by one year. The median interval between the first positive ctDNA and clinical recurrence was 2.7 months. Clinical recurrences usually occurred within 3 months for ctDNA levels above 10 molecules/mL, within 6 months for levels between 1-10 molecules/mL, and within 9 months for levels below 1 molecule/mL.
Limitations: In this real-world study, there was variability in timing and frequency of follow-up examinations, imaging, and ctDNA testing, although most patients were followed with both ctDNA and imaging.
Conclusions: A positive ctDNA test detects MCC recurrence approximately 3 months earlier than imaging. Negative ctDNA can help reduce imaging frequency through serial ctDNA monitoring, while positive ctDNA warrants closer patient follow-up.
Keywords: Merkel cell carcinoma; biomarker; circulating tumor DNA; ctDNA; lead time; recurrence.
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