On Oct. 2, 2026, researchers at Stanford Medicine and the VA Palo Alto Health Care System announced they have devised a simple urine test that can diagnose people with bladder cancer more accurately than current standard methods. The test also allows physicians to not only assess the cancer’s response to treatment but also predict whether immunotherapy or chemotherapy is likely to be most effective for each patient. The test is unique in that it measures RNA messages shed by tumor cells into urine, rather than hunting for cancer-related mutations in DNA as most blood and urine liquid biopsies do. Because RNA reflects which genes a cancer cell is actively using, it captures a tumor’s behavior in addition to its presence.

“Measuring tumor DNA in urine can tell us whether a cancer is present,” said Maximilian Diehn, MD, PhD, the Jack, Lulu, and Sam Willson Professor and a professor of radiation oncology. “Analyzing RNA can tell us not only whether a cancer is present but also what it’s doing.” Diehn shares senior authorship of the study, published in Nature Medicine, with Joseph Liao, MD, the Kathryn Simmons Stamey Professor and chair of the department of urology, and Ash Alizadeh, MD, PhD, the Moghadam Family Professor. Graduate student Kevin J. Liu is the lead author of the research.

About 85,000 people in the United States are diagnosed each year with bladder cancer, which is prone to recurrence and expensive to monitor. Diagnosis and surveillance currently rely on cystoscopy, in which an endoscope is threaded into the bladder to look for suspicious tissue – a procedure that can miss up to 30% of cancer cases. High-risk patients with a history of non-muscle-invasive bladder cancer may need to undergo the surveillance procedure every three months. After surgery to remove a tumor, many patients are treated with a weakened strain of the bacterium used in tuberculosis vaccines called Bacillus Calmette-Guérin, or BCG. BCG is instilled directly into the bladder through a catheter once a week for six weeks and may be repeated as maintenance for up to three ye

Normal bladder lining cells often accumulate their own mutations that overlap with those in a patient’s actual tumor. A DNA test can mistake these bystander mutations – known as the field effect – for cancer, and correcting for them often requires first sequencing a patient’s tumor and normal tissue to learn which mutations to track and which to disregard. In contrast, because RNA messages reflect overall gene activity rather than individual mutations, RNA tests don’t require matched tumor samples.ars. BCG stimulates the patient’s immune system to destroy any lingering cancer cells. But the treatment doesn’t work for everyone – some tumors simply lack the underlying immune activity needed to spark an effective attack – and there’s been no reliable way to tell in advance who will benefit.

Designing a urine-based test focused on RNA rather than DNA, however, was difficult because RNA molecules in urine are fragmented and relatively rare. The researchers adapted a genetic sequencing method originally designed for RNA in blood plasma and designed a custom gene panel to identify RNA messages that are rare in healthy urine but abundant when a patient has genitourinary tumors. Applied to samples from patients with bladder, kidney, and prostate cancer, the resulting test, called uRARE-seq (for urine random priming and affinity capture of cell-free RNA fragments for enrichment analysis by sequencing), closely tracked the biology of the tumors and could distinguish low-grade from high-grade bladder cancer.

In a study of 683 urine samples from patients and healthy volunteers, the test correctly identified 95% of people with localized bladder cancer and gave a clean bill of health to 90% of those who did not, outperforming both standard urine cytology (in which urine is examined through a microscope to identify cancerous cells) and a DNA-based urine test. It also identified residual disease left behind after surgery and BCG immunotherapy. The researchers found that patients who subsequently responded to BCG had pre-treatment urine RNA messages rich in genes involved in T-cell and immune-signaling activity; those who didn’t instead showed signs of rapidly dividing tumor cells. Leveraging this finding, they developed a biomarker that predicted with high accuracy whether tumors were more likely to respond to immunotherapy versus chemotherapy, which is currently a second-line treatment if BCG is not successful or is unavailable.

Identifying who is most likely to respond to BCG treatment is critical. BCG is manufactured by a single global supplier, and shortages are common, forcing urologists to ration it among patients. A validated version of the test could let doctors reserve BCG for those patients who are most likely to benefit from it and move others to chemotherapy sooner. The researchers plan to validate uRARE-seq in larger, prospective trials at multiple centers, with the aim of bringing personalized treatment to bladder cancer patients.