Polyomavirus Antibodies for Merkel Cell Carcinoma Recurrence Detection

Importance: Merkel cell carcinoma (MCC) is typically caused by the Merkel cell polyomavirus (MCPyV) and recurs in 40% of patients. Half of patients with MCC produce antibodies to MCPyV oncoproteins, the titers of which rise with disease recurrence and fall after successful treatment. Objective: To assess the utility of MCPyV oncoprotein antibodies for early detection of first recurrence of MCC in a real-world clinical setting. Design, Setting, and Participants: This prospective cohort study used a data and specimen repository from 2008 to 2020 in Seattle, Washington. Patients with MCC with locoregional disease underwent serum antibody testing at diagnosis. Statistical analysis was conducted between 2020 and 2025. Main Outcomes and Measures: The first posttreatment titer was necessary to establish a trend and was not used to assess risk (deferred). Subsequent titers were defined as (1) falling or negative, (2) rising, or (3) stable compared with the preceding titer. Results: Among the 503 patients in the cohort (median IQR age at diagnosis, 70 62-77 years; 40% female), 1402 tests were performed; 247 (49%) were seropositive. A total of 877 were falling or negative, 62 were rising, 317 were stable, and 146 were deferred. Median (IQR) follow-up was 4.2 (1.8-7.4) years. On average, antibody titers fell by half every 3 months among patients not experiencing a recurrence. After a falling or negative titer, the likelihood that a given patient would remain recurrence-free for 3 months was 99.3% (95% CI, 98.6%-99.8%). In contrast, after a single rising titer, the risk of recurrence over the next 3 months was 36% (95% CI, 22%-52%), increasing to 58% (95% CI, 40%-78%) by 12 months and 68% (95% CI, 48%-86%) by 24 months. A rising titer preceded clinical or radiographic evidence of recurrence in 57% of cases (20/35). The median (IQR) interval between a rising titer and clinical disease detection was 3.7 (1.1-7.5) months, with 90% of recurrences (18/20) occurring within 14 months of the rising titer. Recurrences and antibody titers were analyzed in 196 patients with multiple blood draws. Conclusions and Relevance: In this prospective cohort study, given a negative predictive value of 99.3%, a falling or negative titer may obviate the need for imaging, reducing radiation and contrast dye exposure. Conversely, a rising antibody titer should trigger closer follow-up, as it may lead to earlier detection of clinical recurrence and initiation of therapy.