Integrating ctDNA in NMIBC: Promise and practical challenges

In this video, Laura Bukavina, MD, MSc, MPH, and Betty Wang, MD, discuss the intersection of circulating tumor DNA (ctDNA) monitoring with emerging therapies for non–muscle invasive bladder cancer (NMIBC), particularly within high-risk patient populations. They are co-authors of a recent European Urology Oncology paper regarding ctDNA and NMIBC. Bukavina emphasizes that ctDNA should be integrated into clinical trials as an exploratory biomarker, allowing for better patient stratification. Patients with positive ctDNA results following salvage therapy failure may represent a distinct group that benefits differently from novel treatments. Wang adds that ctDNA positivity is often associated with more advanced disease, raising the question of whether neoadjuvant chemotherapy might be beneficial even in NMIBC patients showing ctDNA positivity—despite current guidelines limiting that approach to muscle-invasive disease. 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 in Cleveland, Ohio, and Wang is a Society of Urologic Oncology fellow at Cleveland Clinic.

From a practical standpoint, integrating ctDNA into clinical practice poses challenges. Wang notes the initial assay requires tissue sequencing and custom assay development, which can delay results by several weeks. However, subsequent monitoring is faster, typically within days. Clear institutional guidelines are essential to identify appropriate candidates—namely, patients with high-risk NMIBC, rather than those with low-grade tumors.

Bukavina adds that logistical issues, such as integration with electronic medical records and the need for manual ordering via secondary portals, can hinder adoption. Financial considerations also matter: Although insurance often covers testing, the focus should remain on patients most likely to benefit, such as those who are BCG-unresponsive, rather than BCG-naïve individuals.

The key takeaway for urologists is to embrace ctDNA as a valuable, emerging tool—particularly in high-risk and treatment-refractory cases. Wang encourages centers with access to the assay to use it judiciously, whereas Bukavina urges clinicians not to fear innovation but to find ways to integrate these tools into routine care to improve patient outcomes.

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