Comparison of surveillance circulating tumor DNA and Merkel polyomavirus antibody titer for detection of Merkel cell carcinoma recurrence.

9574 Background: Circulating tumor DNA (ctDNA) is emerging as a robust biomarker for detecting recurrences in Merkel cell carcinoma (MCC). This study aims to compare the performance of ctDNA against the Merkel polyomavirus antibody titer (AMERK) test in predicting MCC recurrence risk. Methods: We conducted a longitudinal, multi-center observational study involving 171 MCC patients undergoing disease surveillance, including serial ctDNA and AMERK testing (median testing interval: 92 days). All patients had detectable antibodies by AMERK at initial diagnosis and both tests were conducted within 45 days of each other. ctDNA tests were classified as positive if ctDNA was > 0 MTM/mL. An AMERK test was positive if antibody titers rose ≥ 30% from the prior titer. Clinical recurrences were identified through routine imaging and clinical examinations. The diagnostic performance of ctDNA and AMERK tests was assessed using positive and negative predictive values (PPV and NPV), recurrence-free survival after any positive test vs. all negative tests, and corresponding hazard ratios (HRs) from Cox regression. Results: 718 pairs of ctDNA and AMERK tests were collected from 171 patients. Over a median follow-up of 445 days, there were 38 clinical recurrences, 91/718 (13%) positive ctDNA tests, and 73/718 (10%) positive AMERK tests. A significantly increased clinical recurrence rate was observed in patients with a positive ctDNA test compared to those with consistently negative results (HR: 27.4, 95%CI: 11.0-68.3) (Table 1). Although a positive AMERK test was similarly associated with higher clinical recurrence (HR: 5.8, 95%CI: 3.0-11.1), the rate was distinctly lower than that for a positive ctDNA test (HR: 5.8 vs. 27.4; p < 0.001). The PPV for clinical recurrence at 1 year after a positive test was significantly higher for ctDNA vs. AMERK (PPV: 73% [95% CI: 58-84%] vs. 51% [95% CI: 29-70%]; p=0.014). NPV for recurrence within 4 months of a negative test for the ctDNA test was similarly higher for ctDNA vs. AMERK (NPV: 98% [95% CI: 97-99%] vs. 95% [95% CI: 92-97%]; p=0.001). The median lead time between the first positive test and a clinically detected recurrence was 3.1 months for ctDNA (among 30 recurrences preceded by a positive test) and 1.9 months for AMERK (among 19 recurrences preceded by a positive test) (p=0.063). Conclusions: Our results indicate that, in a cohort of AMERK positive patients, ctDNA outperforms AMERK for detection of MCC recurrence. ctDNA may be a viable alternative to AMERK in clinical practice and may better identify high-risk patients who benefit from more aggressive monitoring or adjuvant therapy trials. Hazard ratios for subsequent MCC clinical recurrence: Comparison of positive ctDNA and AMERK tests. Test HR (95% CI) P-value Positive ctDNA 27.4 (11.0, 68.3) <0.001 Positive AMERK 5.8 (3.0, 11.1) <0.001 Difference (ctDNA / AMERK) 4.7 (2.1, 15.9) <0.001