Investigators assess ctDNA’s role in NMIBC

For a recent study published in European Urology Oncology, researchers investigated the use of circulating tumor DNA (ctDNA) in patients with non–muscle invasive bladder cancer (NMIBC).¹ The investigators used the Signatera assay to analyze ctDNA. The study included 23 patients treated between August 2024 and April 2025. In an interview with Urology Times, study authors Betty Wang, MD, and Laura Bukavina, MD, MPH, MSc, provided an overview of the paper. Wang is a Society of Urologic Oncology fellow at Cleveland Clinic in Cleveland, Ohio and Bukavina is an assistant professor of urologic oncology at Cleveland Clinic Glickman Urologic Institute, and translational science lead in genitourinary oncology at Cleveland Clinic Lerner College of Medicine.

A notable finding was that 35% of these NMIBC patients exhibited ctDNA positivity, which was an unexpected and surprising result for the investigators. The patient cohort included individuals who were BCG-naive (high-risk), had remote BCG treatment (over a year prior), or were actively undergoing BCG or salvage intravesical therapy.

The study also presented 3 case illustrations demonstrating how ctDNA aided in patient workups. Two cases showed positive utility, whereas a third presented a confusing ctDNA finding that was later clarified as indicative of a patient's need for further intervention.

The uniqueness of this study lies in its focus on NMIBC, as the role of ctDNA is well-established in more advanced diseases but less so in the non–muscle invasive space, where systemic circulating tumor DNA is typically considered unlikely. The investigators were particularly interested in very high-risk patients, specifically those with T1 plus or minus carcinoma in situ. The majority of ctDNA-positive patients in this study had either been exposed to BCG or were unresponsive to it.

Although ctDNA positivity rates in more advanced diseases often exceed 50%, the 30% to 35% positivity in this NMIBC cohort is still significant, considering NMIBC is generally viewed as localized and non-aggressive. A critical finding was that positive ctDNA in NMIBC cases consistently led to upstaging of the patient at the time of surgery. This upstaging included diagnoses of lymph node-positive disease or more advanced muscle involvement. Therefore, ctDNA is considered a crucial prognostic factor, especially with the emergence of new therapies in this field.

REFERENCE

1. Wang B, Davis LE, Weight CF, Abouassaly R, Bukavina L. Real-world experience with a commercial circulating tumor DNA assay in non-muscle-invasive bladder cancer. Eur Urol Oncol. 2025 Jun 13:S2588-9311(25)00165-8. doi:10.1016/j.euo.2025.05.019