A Urine RNA Test Detected 95% of Localized Bladder Cancers and Predicted Who Would Respond to BCG
Stanford researchers' urine test, uRARE-seq, detected localized bladder cancer with 95% sensitivity at 90% specificity in 683 samples and flagged which patients were more likely to respond to BCG immunotherapy.
A urine test developed at Stanford Medicine detected localized bladder cancer with 95% sensitivity at 90% specificity in a study of 683 urine samples, and it also helped predict which patients would respond to BCG immunotherapy rather than chemotherapy, according to Stanford Medicine. The results were published October 2 in Nature Medicine.
Reading tumor RNA instead of tumor DNA
The test, called uRARE-seq, looks for RNA messages that tumor cells shed into urine, a design the researchers chose because RNA shows what a tumor is doing as well as whether it is there. “Measuring tumor DNA in urine can tell us whether a cancer is present — but analyzing RNA can tell us not only whether a cancer is present — but also what it's doing,” said Maximilian Diehn, who led the work with Joseph Liao and Ash Alizadeh. It outperformed standard urine cytology and DNA-based urine tests.
A gap in how bladder cancer is monitored today
Current surveillance relies on cystoscopy, in which a camera is passed into the bladder, and high-risk patients undergo it about every three months. Stanford says it can miss up to 30% of cancers. Bladder cancer patients are also often treated with BCG, and manufacturing bottlenecks make it important to pick the right patients for it.
A biomarker for choosing between BCG and chemotherapy
Patients who responded to BCG had pre-treatment urine RNA rich in genes tied to T-cell and immune signaling, while non-responders showed signs of rapidly dividing tumor cells. According to the Nature Medicine paper, a biomarker built on this pattern predicted response with an area under the curve of 0.93 and was strongly associated with risk of recurrence.
Still a research test
The findings need to be confirmed in larger, prospective, multi-center trials before the test can be used in clinics, and cystoscopy remains the standard for now. Kevin J. Liu is the study's lead author, and the work was done by teams at Stanford Medicine and the VA Palo Alto Health Care System.
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