Residual Disease Test Predicts Merkel Cell Carcinoma Recurrence Earlier Than Antibody Assay

Merkel cell carcinoma is a rare, aggressive skin cancer with a substantial risk of relapse, occurring in about 40% of patients. Surveillance remains challenging because widely used serologic monitoring applies only to virus-positive disease and may be less reliable after immunotherapy or multiple recurrences. A new residual disease test now demonstrates earlier and more accurate recurrence prediction than a commonly used antibody assay in a head-to-head study.

Natera’s Signatera test was evaluated against the Merkel cell polyomavirus antibody test (AMERK) in a study published in JAMA Dermatology on July 8, 2026. The analysis compared both methods for predicting recurrence and the time advantage provided before clinical relapse. In this cohort, the Signatera test was identified as a significantly stronger predictor of recurrence and as offering earlier detection.

Image: Signatera is a personalized ctDNA-based MRD assay designed to detect relapse earlier than standard-of-care tools (Photo courtesy of Natera)

The study was a retrospective analysis of a prospective, multicenter, head-to-head comparison including 169 patients with Merkel cell carcinoma. Signatera outperformed AMERK across sensitivity, positive predictive value, negative predictive value, and lead time to recurrence. The test’s clinical validation has been published across all patients regardless of viral status, and it has been included in National Comprehensive Cancer Network (NCCN) Guidelines as a recommendation for surveillance monitoring.

Key performance findings included a higher sensitivity for detecting recurrence with Signatera compared with AMERK (90% versus 55%). In patients where both tests identified recurrence, Signatera provided a longer median lead time to detection (5.1 months versus 2.1 months). The difference in predictive strength between the assays was significant (hazard ratio difference 6.6; p < 0.001), indicating improved risk stratification within the study population.

“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. 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,” said Lisa Zaba, M.D., Ph.D., 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.