Background Serum antibodies to the Merkel oncoprotein (AMERK) are detectable in approximately 50% of patients with Merkel cell carcinoma (MCC) and can be used to monitor for recurrence. The objective of this study was to characterize AMERK levels in patients receiving curative‐intent radiation therapy (RT) for MCC and identify associations between AMERK and recurrence. Methods This was a retrospective study of patients with MCC who had baseline AMERK measurements before they received curative‐intent RT from 2010 to 2020. Event‐free survival (EFS) was calculated using the Kaplan–Meier method and Cox regression. The cumulative incidence of MCC‐related recurrence (CIMR) was analyzed with death as a competing risk and the Gray test. Results The authors identified 88 patients who had baseline AMERK measurements, including 52 (59%) with detectable levels. AMERK positivity was associated with younger median age (67.8 vs. 72.0 years; p = .02) and tumor site ( p = 0.02), with lower rates for those who had disease in the head/neck region (17.3% vs. 44.4%). EFS (71.3% vs. 60.4%; p = .30) and CIMR (24.4% vs. 39.6%; p = .23) were more favorable in AMERK‐positive patients. Two patients had recurrences in the RT field, and both were AMERK‐negative at baseline. The median time to AMERK nadir after RT was 11.2 months; and, in a 6‐month post‐RT landmark analysis, the proportion of patients who were AMERK‐positive who became negative or who had levels that decreased by ≥50% were not associated with EFS (87.1% vs. 85.0%; p = .90) or CIMR (12.9% vs. 15.0%; p = .62). Conclusions Positive AMERK baseline levels were correlated with younger age at MCC diagnosis and nonhead and neck tumor location, possibly related to the distribution of viral etiology. A specific post‐RT AMERK decline correlating with EFS could not be identified.
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