Urine cell-free RNA for bladder cancer detection and treatment response prediction

A urinary test developed by researchers at Stanford Medicine and the VA Palo Alto Health Care System can diagnose bladder cancer more accurately than current methods, according to an article published in Nature Medicine. This innovative test not only assesses the cancer's response to treatment but also predicts which immunotherapy or chemotherapy would be most effective for each patient.

The test measures RNA messages shed by tumor cells into urine, providing a biological signature of disease rather than an exact likeness of tumor mutations, which DNA tests require. This eliminates the "field effect" problem where normal bladder lining cells can be mistaken for actual cancer, and it does not require matched tumor samples.

Bladder cancer is prevalent, with about 85,000 people diagnosed annually in the United States, and it often recurs, making surveillance expensive and challenging. Diagnosis currently relies on a cystoscopy, which can miss up to 30% of cases. High-risk patients may need surveillance every three months. After tumor removal, many patients receive Bacillus Calmette-Guérin (BCG), a weakened bacterial strain instilled into the bladder weekly for six weeks, with possible repeat treatments.

However, BCG doesn't work for everyone, as some tumors lack the necessary immune activity, and there's been no reliable way to predict in advance who will benefit.

The uRARE-seq test, developed by measuring RNA messages in urine, outperformed standard urine cytology and a DNA-based urine test in a study of 683 urine samples. It identified 95% of people with localized bladder cancer and classified 90% of those without it. Additionally, it detected residual disease left after surgery and identified patients who responded better to BCG immunotherapy or needed chemotherapy. This test could help doctors reserve BCG for patients most likely to benefit, improving treatment outcomes.