This multicenter cohort study (3 US academic centers, April 2020–March 2024) compared ctDNA vs. MCPyV oncoprotein antibody testing for detecting recurrence in 169 stage I–IV MCC patients who were disease-free at baseline and had detectable MCPyV antibodies at diagnosis, using 703 serial paired tests over a median follow-up of 483 days.
ctDNA outperformed antibody testing on all metrics: PPV at 365 days 73% vs. 52% (P=.02), NPV at 90 days 99% vs. 97% (P=.001), and HR 47.9 vs. 7.3 (HR ratio 6.6; P<.001). Adding antibody testing to ctDNA identified only 1 additional recurrence beyond ctDNA alone across 32 patients with recurrence.
- Only patients with detectable MCPyV antibodies at diagnosis were included, so findings may not apply to virus-negative (MCPyV-negative) MCC. - Median follow-up was ~16 months; longer-term performance is unknown. - Study limited to academic centers, which may limit generalizability to community settings.
For MCC patients with detectable MCPyV antibodies, ctDNA is a more reliable surveillance biomarker than antibody testing — consider prioritizing ctDNA for routine recurrence monitoring. Adding antibody testing on top of ctDNA provides minimal incremental value.