Stanford Researchers Develop uRARE-seq Urine Test for Bladder Cancer

Researchers at Stanford Medicine and the VA Palo Alto Health Care System have developed a non-invasive urine test called uRARE-seq that identifies bladder cancer by measuring cell-free RNA fragments. Published on October 2, 2026, in Nature Medicine, the assay correctly detected 95 percent of localized bladder cancer cases in a study.

Stanford Researchers Develop uRARE-seq to Measure Cell-Free RNA

A team of investigators at Stanford Medicine and the VA Palo Alto Health Care System has introduced a novel liquid biopsy method designed to diagnose bladder cancer and guide treatment decisions from a simple urine sample. The test, known as uRARE-seq, measures cell-free RNA fragments shed by tumors rather than hunting for mutated DNA.

Most blood and urine liquid biopsies search for cancer-associated DNA mutations. However, the Stanford assay takes a different path by analyzing RNA messages, which reflect the genes a cancer cell actively expresses. This captures tumor behavior alongside its physical presence.

The research was led by graduate student Kevin J. Liu and co-authored by senior investigators Maximilian Diehn, Joseph Liao, and Ash Alizadeh. The findings were published on October 2, 2026, in the journal Nature Medicine.

Study Results and Diagnostic Accuracy Across 683 Samples

To evaluate the assay, the research team analyzed 683 urine samples collected from both cancer patients and healthy volunteers at Stanford University and the VA Palo Alto Health Care System. The test correctly identified 95 percent of individuals with localized bladder cancer and returned clean results for 90 percent of participants without the disease.

The assay also detected non-muscle-invasive bladder cancer, representing early-stage tumors that have not yet breached the bladder wall and which standard cytology procedures can miss.

The test also avoids a well-documented obstacle in urine DNA testing known as the field effect. Normal bladder lining cells often accumulate bystander mutations that overlap with actual tumor mutations, which can lead DNA tests to produce false positives unless the patient’s specific tumor is sequenced beforehand. Because RNA reflects overall gene activity rather than individual point mutations, uRARE-seq does not require matched tumor tissue samples.

Treatment Prediction and Monitoring Residual Disease Following BCG Therapy

Beyond initial detection, the assay demonstrated an ability to track residual disease following surgery and to predict patient response to Bacillus Calmette-Guérin (BCG) immunotherapy. BCG is a weakened tuberculosis bacterial strain instilled directly into the bladder via catheter to stimulate the immune system against lingering cancer cells. However, the treatment does not work for every patient.

Scientists Develop Simple Test That Detects 95% of a Common Cancer in Study - Newsweek — Photo: Newsweek

Researchers discovered that patients who exhibited a complete molecular response to BCG showed stronger T-cell and immune-signaling gene expression signatures in their pretreatment urine. Conversely, patients who showed molecular residual disease presented higher expression of proliferation-associated genes.

“These findings are significant as identification of T-cell signatures in urine which predict BCG response could help to select those patients who are unresponsive to BCG, thus identifying patients who may need alternative treatments.”

Dr. Daniel Petrylak

Using these molecular differences, the investigators developed a model predicting the likelihood of response to BCG versus intravesical chemotherapy. In pretreatment urine samples from 114 patients, the model scored 0.93 on a scale where 1.0 represents perfect discrimination between treatment responses.

Next Steps for Clinical Validation and Commercialization

Approximately 85,000 individuals are diagnosed with bladder cancer each year in the United States. Current surveillance methods rely heavily on cystoscopy, an invasive endoscopic procedure that can miss up to 30 percent of cases and must be repeated frequently for high-risk patients.

While the initial data from Stanford are promising, independent experts emphasize that further evaluation is necessary.