Urine RNA test detects 95% of localized bladder cancers

Clinical takeaway: Urine RNA testing may eventually help urologists reserve scarce Bacillus Calmette-Guérin for likely responders and move others to chemotherapy sooner. Watch for prospective validation before it informs those decisions. 

Urologists lean on cystoscopy to find bladder cancer and to catch its return, yet the scope can miss up to 30% of cancers. Patients at high risk of recurrence may go back every three months, a schedule that's taxing for them and expensive to sustain. Treatment adds its own uncertainty: after surgery, many patients receive Bacillus Calmette-Guérin (BCG), a weakened bacterial strain instilled into the bladder to rally the immune system, and no reliable test tells urologists in advance who it will help. 

Blood and urine liquid biopsies have mostly focused on cancer-related DNA mutations, but bladder complicates that approach. Normal lining cells accumulate mutations that overlap with a tumor's, so a DNA test can mistake those bystander changes for cancer. Avoiding that error usually means sequencing the patient's tumor and normal tissue first. RNA sidesteps the problem because it reflects which genes a cell is actively using, so no matched tumor sample is needed. That readout also shows what a tumor is doing, including the immune activity that may shape whether BCG works. This recent study tests an RNA-based urine assay for cancer detection and treatment selection. 

The test correctly identified 95% of people with localized bladder cancer and cleared 90% of those without it. Cytology and a DNA-based urine test both fell short of that accuracy. The RNA profile also separated low-grade from high-grade bladder cancer, and it picked up residual disease left after surgery and BCG immunotherapy. 

Treatment response followed a second pattern. Before treatment, urine RNA from patients who later responded to BCG was rich in genes tied to T-cell and immune-signaling activity, while RNA from nonresponders pointed to rapidly dividing tumor cells. The authors built a biomarker from that contrast and report that it predicted with high accuracy whether a tumor was likelier to respond to immunotherapy or to chemotherapy, the usual second-line option when BCG fails or isn't available. 

The team tested 683 urine samples from patients and healthy volunteers with an RNA sequencing assay adapted from a blood plasma method, using a custom panel of genes that are rare in healthy urine and abundant in genitourinary tumors. Urine cytology and a DNA-based urine test served as the comparators. 

The authors plan to confirm the detection results and the treatment-response biomarker in larger, prospective trials at multiple centers, which would show whether both hold in patients enrolled going forward. 

"There are currently no biomarkers at all that are recommended or approved for surveillance. These treatments are incredibly taxing — physically and financially," said Joseph Liao, MD, chair of urology at Stanford Medicine and a senior author of the study. "If we can guide those choices, we have the potential to help both patients and clinicians." 

Source: Liu KJ, et al. (2026 Oct 2) Nat Med. Urine cell-free RNA for bladder cancer detection and treatment response prediction