Our study is the first to report institutional experience using a commercially available, tumor-informed ctDNA assay (Signatera™) for patients with high-risk NMIBC. Unlike previously published work that utilized in-house sequencing techniques, our use of a validated commercial platform allowed for scalable, real-world implementation, while simultaneously generating whole-exome sequencing data to support future precision oncology efforts. At our center, ctDNA testing was made available at no cost to patients and was smoothly integrated into clinical workflows through industry partnership.
In our consecutive cohort of 23 patients collected over a 9-month period, ctDNA was positive in 35%. In two illustrative cases, ctDNA positivity directly influenced care, prompting early imaging, expedited diagnostic cystoscopy, and ultimately the decision to proceed with radical cystectomy and systemic therapy. These examples highlight ctDNA’s potential as a non-invasive tool for detecting molecular residual disease, facilitating earlier detection of recurrence or progression when standard surveillance might otherwise delay intervention.
Given the high stakes of undertreating aggressive NMIBC and the rapid evolution of the therapeutic landscape, we believe ctDNA could play a critical role in refining patient selection for salvage therapies, identifying candidates for early cystectomy, and potentially even supporting the use of upfront systemic therapy in select cases.
That said, many unanswered questions remain. Should ctDNA be used universally in NMIBC or reserved for those with high-risk features? Likely the latter. What is the optimal frequency of surveillance? We know that the lead time of ctDNA over radiographic progression in advanced urothelial carcinoma is approximately 3 months. Does NMIBC follow the same temporal pattern? What is the true negative predictive value, and how do we counsel patients with discordant findings between imaging, pathology, and ctDNA (as shown in the third case of our manuscript)? Are there specific ctDNA thresholds that could guide whether to delay or avoid radical cystectomy, or to initiate systemic therapy pre-emptively for cytoreduction? These are questions that future prospective, multi-institutional studies must address. We hope our real-world data can serve as a foundation for ongoing investigation and help move the field closer toward integrating ctDNA into routine NMIBC care.
Written by: Betty Wang,1 Laura E. Davis,2 Christopher J. Weight,1 Robert Abouassaly,1 Laura Bukavina1
- Glickman Urologic Institute, Cleveland Clinic, Cleveland, OH
- Case Western University Hospitals, Urology Institute, Cleveland, OH