Dr Linscott on the Use of Urinary Cell-free Tumor DNA to Predict MRD in High-Risk NMIBC

Joshua Linscott, MD, PhD, urologic oncologist, Moffitt Cancer Center, discusses the background of a clinical trial that investigated the use of urinary cell-free tumor DNA (utDNA) to predict minimal residual disease (MRD) prior to repeat transurethral resection of bladder tumors (rTURBT) in patients with high-risk non-muscle invasive bladder cancer (NMIBC).

This prospective study focused on patients who underwent either initial TURBT or, more commonly, rTURBT, as part of their treatment for high-risk NMIBC, Linscott begins. Investigators at Moffitt Cancer Center collect urine samples from these patients throughout their treatment. The goal of this study was to assess the use of utDNA to detect MRD and evaluate its potential role in ongoing surveillance, Linscott explains. The study investigated whether tumor fraction and copy number burden (CNB) from utDNA can serve as reliable biomarkers for detecting MRD prior to rTURBT, he adds.

The field of cell-free DNA is rapidly advancing, with implications across various cancer types, and it is especially promising in bladder cancer, Linscott continues. Numerous studies have demonstrated that bladder tumors release cell-free DNA into the urine, making the urine an accessible source for detecting genomic alterations in localized disease, he emphasizes. In early-stage bladder cancer, plasma or circulating tumor DNA levels tend to be lower and less detectable, Linscott expands. However, since urine is constantly in contact with bladder tumors, it provides a more reliable source for detecting utDNA and assessing tumor activity, he adds. This study used whole-genome sequencing to detect utDNA and estimate CNB, along with MRD sequencing probes that were personalized to each patient and derived from somatic variants in their initial tissue samples, Linscott notes. Ultimately, this approach could revolutionize the way oncologists monitor MRD and disease progression, offering a non-invasive and highly sensitive method for assessing tumor activity in patients with bladder cancer, he concludes.