Dr Linscott on Future Directions for utDNA Research in Bladder Cancer

Joshua Linscott, MD, PhD, urologic oncology fellow, Moffitt Cancer Center, discusses the use of tumor fraction and copy number burden from urinary cell-free tumor DNA (utDNA) to predict minimal residual disease (MRD) prior to standard repeat transurethral resection of bladder tumors (rTURBT) in high-risk non–muscle-invasive bladder cancer (NMIBC).

A study enrolled and collected urine samples from 53 patients with high-risk NMIBC prior to undergoing rTURBT. Investigators then measured tumor fraction and copy number burden levels in utDNA derived from the samples. Findings from this study, which were presented at the 2024 ASCO Annual Meeting, demonstrated that the utDNA technology detected MRD in 68% of patients. Furthermore, the copy number burden score detected MRD with an overall area under the curve (AUC) of 0.86. In patients with personalized tumor fraction (n = 34), MRD was detected with an AUC of 0.89.

The findings from this study are broadly applicable across bladder cancer research, Linscott begins, adding that this approach could improve patient surveillance and treatment personalization. Although this study was conducted in patients with NMIBC, utDNA results could also be extrapolated to patients with muscle-invasive bladder cancer (MIBC), including those receiving neoadjuvant chemotherapy, he explains.

In the future, Linscott and colleagues may investigate different prognostic signatures to predict which patients with bladder cancer may respond to certain treatments, including those with advanced disease who receive neoadjuvant chemotherapy, he notes. utDNA surveillance may also be used to evaluate whether certain patients with MIBC who achieve a complete response with neoadjuvant chemotherapy may be candidates for bladder-sparing treatment, Linscott emphasizes.

Overall, analysis of utDNA prior to transurethral resection may benefit patients with bladder cancer, ensuring more precise and effective treatment plans, Linscott says. Despite the nascent stage of this technology, its potential is vast and relatively untapped, Linscott concludes.