TOPLINE

Circulating tumor DNA (ctDNA) predicted recurrent Merkel cell carcinoma (MCC) more accurately than Merkel cell polyomavirus (MCPyV) antibody testing in a multicenter cohort study.

METHODOLOGY

• Researchers conducted a multicenter cohort study across three US academic centers involving 169 patients (median age, 72 years; 64% men) with stage I-IV MCC who had detectable MCPyV antibodies and underwent serial testing of both ctDNA and MCPyV antibodies for surveillance between April 2020 and March 2024.
• Patients were clinically disease-free at baseline and underwent paired ctDNA and antibody testing within 45 days of each other; the median testing interval was 96 days over a median follow-up of 483 days.
• A total of 703 paired tests were analyzed; ctDNA was considered positive if mean tumor molecules per mL of plasma values were > 0.00, whereas a rising antibody test was defined as a 30% or greater increase in titer. The combined test was positive if either ctDNA was positive or MCPyV antibodies were rising.
• The primary outcome was clinical recurrence. Predictive performance measures included positive predictive value (PPV), negative predictive value (NPV), and hazard ratios (HRs), comparing ctDNA and antibody testing.

TAKEAWAY

• Over a median follow-up of 483 days, there were 36 clinical recurrences in 32 patients. The risk for recurrence was greater with positive ctDNA results than rising antibody titers (HR, 47.9 vs 7.3; HR ratio, 6.6; P < .001), with ctDNA showing a higher concordance index (0.87 vs 0.70; P < .001).
• ctDNA showed a higher PPV at 365 days than antibody testing (73% vs 52%; P = .02) and a higher NPV at 90 days (99% vs 97%; P = .001).
• The median lead time for ctDNA was longer than that for antibody testing (3.4 months vs 2.3 months; P = .07); ctDNA showed a longer lead time when both tests were positive (5.1 months vs 2.1 months; P = .04).
• Combined ctDNA and antibody testing identified only one additional recurrence compared with ctDNA testing alone, but it produced 131 positive tests vs 94 for ctDNA alone.

IN PRACTICE

“While the use of antibody testing is limited to a subset of patients with virus-positive MCC and who produce measurable MCPyV antibodies, ctDNA is applicable across patients with both virus-positive and virus-negative tumors, pre- and post-immunotherapy exposure, and pre- and post-first recurrence, making it a more broadly reliable biomarker,” the authors of the study concluded. These findings “support the potential of ctDNA to redefine MCC surveillance strategies, reduce reliance on routine surveillance imaging, and guide timely interventions, hypotheses that warrant validation in prospective, standardized studies,” they added.

SOURCE

The study was led by Manisha Thakuria, MD, Department of Dermatology, Brigham and Women’s Hospital, Boston, and was published online on July 8 in JAMA Dermatology.

LIMITATIONS

Variable assay timing and imaging frequency, along with exclusion of patients without paired tests within 45 days, may have introduced bias. Positive results could have prompted closer surveillance, shortening lead times. Additionally, some performance estimates had wide CIs, so results warranted cautious interpretation.

DISCLOSURES

This research was supported by funding from the Kuni Foundation, the Lisa Zaba grateful patient gift fund at Stanford University, the Manisha Thakuria grateful patient fund, the Ann W. Silk grateful patient fund, and the Dargie Family Fund, along with grants from the National Institutes of Health/National Cancer Institute. Several authors reported receiving funding, grants, royalties, consulting fees, or clinical trial support from various companies, including Regeneron, Sun Pharma, Immunocore, Checkmate Therapeutics, Marengo, and Kezar Life Sciences. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.