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Can ctDNA detect molecular residual disease in NMIBC?

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Betty Wang, MD, said she envisions ctDNA integrating into existing surveillance protocols for patients with high-risk NMIBC.

In this video, Betty Wang, MD, and Laura Bukavina, MD, MPH, MSc, discuss the promising role of circulating tumor DNA (ctDNA) in the early detection and management of non–muscle-invasive bladder cancer (NMIBC), particularly for identifying molecular residual disease. Their conversation highlights a real-world study using a commercial ctDNA assay in NMIBC patients, which aimed to define its previously undefined utility in this cancer type.1

Wang said she envisions ctDNA integrating into existing surveillance protocols for patients with high-risk NMIBC, such as those with T1 high-grade disease undergoing intravesical therapy or those with BCG-unresponsive disease. She suggests checking ctDNA at the same intervals as maintenance intravesical therapy, for example, every 3 or 6 months for BCG. The study found ctDNA in 35% of NMIBC patients, demonstrating its potential for early detection and treatment guidance, especially in BCG-unresponsive cases.

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    A positive ctDNA result, as shown in their series where every positive patient was upstaged, would prompt cross-sectional imaging (like an MRI of the bladder), upper tract evaluation, and a re-transurethral resection of bladder tumor or cystoscopy with bladder biopsy, even if imaging is negative. This proactive approach aims to find recurrence or progression early and intervene swiftly. Bukavina emphasizes that ctDNA can detect disease much earlier than radiographic imaging. This early detection can help guide treatment decisions, ensuring that patients with localized disease receive appropriate surgical intervention (cystectomy), whereas those with systemic metastasis receive upfront systemic therapy rather than diagnostic cystectomy, ultimately improving sensitivity of imaging and treatment outcomes. Further prospective studies are needed to validate ctDNA's role in risk stratification and treatment optimization.

    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

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