Circulating tumor DNA level is associated with time to clinical recurrence in Merkel cell carcinoma: Implications for patient management

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 1 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 1 year. The median lead time 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.