ctDNA vs Antibody Testing for the Detection of Recurrent MCC

By: JNCCN 360 Staff
Posted: Thursday, July 23, 2026

A prospective, multicenter study in Merkel cell carcinoma (MCC) evaluated the performance of a circulating tumor DNA (ctDNA) test gainst the Merkel cell polyomavirus antibody test (AMERK), finding the ctDNA method—developed by Signatera—to be a significantly stronger predictor of recurrence. ctDNA testing also detected relapse earlier than AMERK.

MCC is a rare but aggressive skin cancer that recurs in approximately 40% of patients. Despite its severity, clinicians have lacked a reliable, universal biomarker to guide surveillance. The AMERK test has been a widely used monitoring tool, but its utility is limited: it can only be used in the roughly 50% of patients with MCC whose tumors are virus-positive, and its accuracy diminishes after immunotherapy exposure or multiple recurrences.

The new study—published by Thakuria et al in JAMA Dermatology—is a retrospective analysis of a prospective, multicenter, head-to-head comparison of ctDNA and AMERK testing in 169 patients with MCC. Key findings include:

• Superior predictive power: ctDNA was a significantly stronger predictor of recurrence than AMERK (hazard ratio difference = 6.6; P < .001), with higher hazard ratios, higher positive predictive value, and higher negative predictive value.
• Higher sensitivity: ctDNA detected recurrence more frequently than AMERK with a sensitivity of 90% vs 55%, respectively.
• Longer lead time: In patients where recurrence was detected by both tests, ctDNA detected recurrence earlier than AMERK with a median lead time of 5.1 months vs 2.1 months, respectively.

“For years, AMERK had been our best available tool, but its inability to function in virus-negative patients and after immunotherapy has been a recognized limitation,” said Lisa Zaba, MD, PhD, Associate Professor of Dermatology and Director of the Merkel Cell Carcinoma Multidisciplinary Clinic at the Stanford University School of Medicine, and corresponding author of the study. “These data demonstrate that Signatera can give clinicians a more precise and earlier signal across all patients, enabling more proactive management of this challenging disease.”

JAMA Dermatology

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