Testing for genetic mutations in urine can detect bladder cancer years before the disease shows clinical symptoms, new research has shown. The study, by researchers from France, Iran and the United States, identified mutations across ten genes that were able to predict the most common type of bladder cancer up to 12 years in advance of diagnosis.

The findings are presented today at the European Association of Urology (EAU) annual Congress in Milan.

Bladder cancer is not a rare disease – it is one of the top ten most common cancers in the UK and the fifth most common in the European Union, with over 200,000 cases in the EU each year. Only around half of those diagnosed with the advanced disease will survive more than five years, mainly due to late diagnosis and recurrence of the disease. By contrast, if their cancer is detected at early stage, more than 80% of patients survive for at least five years.

Lead researcher Dr Florence Le Calvez-Kelm, from the International Agency for Research on Cancer (IARC) in Lyon, said: “Diagnosis of bladder cancer relies on expensive and invasive procedures such as cystoscopy, which involves inserting a camera into the bladder. Having a simpler urine test that could accurately diagnose and even predict the likelihood of cancer years in advance could help to spot more cancers at an early stage and avoid unnecessary cystoscopies in healthy patients.”

The study was based on the UroAmp test, a general urine test that identifies mutations in 60 genes, developed by the Oregon Health Science University spin-out company, Convergent Genomics. Drawing on previous research to identify genetic mutations linked to bladder cancer, the research team narrowed the new test down to focus on mutations within just ten genes.

Working with colleagues from the Tehran University of Medical Sciences in Iran, they trialled the potential new test using samples from the Golestan Cohort Study, which has tracked the health of more than 50,000 participants over ten years, all of whom provided urine samples at recruitment. Forty people within the study developed bladder cancer during that decade, and the team were able to test urine samples from twenty-nine of them, along with samples from 98 other similar participants as controls.

Of the 29 participants who’d developed bladder cancer within the Golestan cohort, the test was able to accurately predict future bladder cancer in 19 (66%) of them, even though urine samples had been taken up to 12 years before clinical diagnosis. Fourteen of these participants were diagnosed with bladder cancer within seven years of urine collection, and the test was able to predict cancer in 12 (86%) of these.  The test was accurately negative in 94 of the 98 participants (96%) who would not develop cancer in the future. Among those where the test was negative but who did eventually develop bladder cancer, no cancer was diagnosed until at least six years after the urine collection.

The test was also trialled with colleagues from Massachusetts General Hospital and Ohio State University using samples from 70 bladder cancer patients and 96 controls, taken prior to a cystoscopy. In contrast with the Golestan study, some of these samples were provided by cancer patients on the day they were diagnosed, rather than many years before.
 
Mutations were found in urine samples from 50 of the 70 patients (71%) whose tumours were visible during the cystoscopy. Some of these were new diagnoses and others involved a cancer recurring. Mutations were not found in 90 of the 96 (94%) patients with a negative cystoscopy.
Dr Le Calvez-Kelm believes these results demonstrate the potential of a genetic urine test for early detection of bladder cancer. She said: “We’ve clearly identified which are the most important acquired genetic mutations that can significantly increase the risk of cancer developing within ten years. Our results were consistent across two very different groups – those with known risk factors undergoing cystoscopy and individuals who were assumed to be healthy.

“Should the results be replicated in larger cohorts, urine tests for these mutations could enable routine screening for high-risk groups, such as smokers or those exposed to known bladder carcinogens through their work."

“This kind of test could also be used when patients come to their doctors with blood in the urine, to help reduce unnecessary cystoscopies. If we can identify bladder cancer early on, before the disease has advanced, then we can save more lives.”

Dr Joost Boormans, a member of the EAU Scientific Congress Office and a urologist at the Erasmus University Medical Center Rotterdam, said: “Research of this nature is very encouraging as it shows that our ability to identify molecular alterations in liquid biopsies such as urine that might indicate cancer is constantly improving.

“While we do need to develop more accurate diagnostics, it’s unlikely that we’ll have a mass screening programme for bladder cancer in the near future. Where a urine test for genetic mutations could show its value in reducing cystoscopies and scans in bladder cancer patients who are being monitored for recurrence, as well as those referred for blood in their urine. A simple urine test would be far easier for patients to undergo than invasive procedures or scans, as well as being less costly for health services.”

Source: EAU