A urine RNA test identified 95 per cent of localised bladder cancers in a study and may help predict response to immunotherapy or chemotherapy.
The test analyses RNA messages shed by tumour cells into urine, rather than searching for cancer-related DNA mutations as most blood and urine liquid biopsy tests do.
Because RNA reflects which genes cancer cells are actively using, researchers say it can provide information about tumour behaviour as well as whether cancer is present.
Maximilian Diehn, professor of radiation oncology at Stanford Medicine, said: “Measuring tumour DNA in urine can tell us whether a cancer is present.”
“Analysing RNA can tell us not only whether a cancer is present — but also what it’s doing.”
Researchers at Stanford Medicine and the VA Palo Alto Health Care System developed the test, called uRARE-seq, by adapting a sequencing method originally designed to analyse RNA in blood plasma.
The team designed a gene panel to detect RNA messages that are uncommon in healthy urine but more abundant in people with genitourinary tumours.
When applied to samples from people with bladder, kidney and prostate cancer, the test tracked tumour biology and distinguished low-grade from high-grade bladder cancer.
In a study of 683 urine samples from patients and healthy volunteers, uRARE-seq correctly identified 95 per cent of people with localised bladder cancer and correctly classified 90 per cent of those without the disease.
It outperformed standard urine cytology, where urine is examined under a microscope for cancerous cells, and a DNA-based urine test.
The test also identified residual disease after surgery and treatment with Bacillus Calmette-Guérin, or BCG, an immunotherapy placed directly into the bladder to stimulate the immune system against cancer cells.
Patients who subsequently responded to BCG had pre-treatment urine RNA signals enriched for genes involved in T-cell and immune-signalling activity.
Those who did not respond instead showed signs associated with rapidly dividing tumour cells.
Using these findings, the researchers developed a biomarker that predicted with high accuracy whether tumours were more likely to respond to immunotherapy or chemotherapy.
Bladder cancer diagnosis and surveillance currently rely partly on cystoscopy, where an endoscope is passed into the bladder to inspect tissue. According to the researchers, the procedure can miss up to 30 per cent of cancer cases.
High-risk patients with a history of non-muscle-invasive bladder cancer may require cystoscopy every three months.
The researchers said DNA-based urine testing can also be complicated because normal bladder lining cells may accumulate mutations similar to those found in tumours.
Ash Alizadeh, professor and senior study author, said: “For DNA-based, tumour-informed approaches, you need to know exactly what the tumour’s mutations look like to track disease.
“RNA doesn’t have that problem. You’re looking for a biological signature of disease, not an exact likeness, and urine is a noninvasive way to accurately detect and track bladder cancer.”
The researchers plan to validate uRARE-seq in larger prospective trials across multiple centres, with the aim of bringing personalised treatment to bladder cancer patients.
Joseph Liao, chair of the department of urology, said: “There are currently no biomarkers at all that are recommended or approved for surveillance. These treatments are incredibly taxing — physically and financially.
“If we can guide those choices, we have the potential to help both patients and clinicians.”
