Urine genetic test predicts bladder cancer years before diagnosis
Testing for genetic mutations in urine can detect bladder cancer years before the disease shows clinical symptoms, new research presented at the annual European Association of Urology (EAU) Congress in Milan, Italy, has shown.
The study, conducted by researchers from France, Iran and the United States.identified mutations in ten genes capable of predicting the most common type of bladder cancer up to 12 years before diagnosis.
Bladder cancer is not a rare disease, as it ranks fifth in the European Union, with over 200,000 cases per year. Only about half of those diagnosed with this advanced disease survive more than five years, mainly due to late diagnosis and disease recurrence. In contrast, if the cancer is detected at an early stage, more than 80% of patients survive at least five years.
Florence Le Calvez-Kelm, MD, a senior researcher at the International Agency for Research on Cancer (IARC) in Lyon, France, explains that “the 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 detect more cancers at an early stage and avoid unnecessary cystoscopies in healthy patients,” he adds.
Mutations of 10 genes
The study was based on the UroAmp test, a general urine test that identifies mutations in 60 genes, developed by Oregon Health Sciences University (USA) spin-off Convergent Genomics. Building on previous research to identify genetic mutations linked to bladder cancer, the research team narrowed the new test to focus on mutations in just ten genes.
In collaboration with colleagues from the Tehran University of Medical Sciences, Iran, tested the potential new test with samples from the Golestan cohort study, which has followed the health of more than 50,000 participants for 10 years, all of whom provided urine samples at the time of screening. Forty people in the study developed bladder cancer during that decade, and the team was able to analyze urine samples from twenty-nine of them, together with samples from 98 other similar participants as controls.
Of the 29 participants who had developed bladder cancer within the Golestan cohort, the test was able to accurately predict future bladder cancer in 19 (66 %) of them, despite the fact that 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 them. The test was negative in 94 of the 98 participants (96 %) who would not develop cancer in the future. Among those in whom the test was negative but who went on to develop bladder cancer, cancer was not diagnosed until at least six years after urine collection.
The test was also tested with colleagues in the Massachusetts General Hospital and Ohio State University. using samples from 70 bladder cancer patients and 96 controls, taken prior to cystoscopy. Unlike the Golestan study, some of these samples were provided by cancer patients on the same day they were diagnosed with the disease, rather than many years earlier.
Mutations were found in urine samples from 50 of the 70 patients (71 %) whose tumors were visible during cystoscopy. In some cases these were new diagnoses and in others recurrent cancer. No mutations were found in 90 of the 96 (94 %) patients with negative cystoscopy.
Up to routine screening
Dr. Le Calvez-Kelm believes these results demonstrate the potential of a urine genetic test for early detection of bladder cancer. “We have clearly identified which are the most important acquired genetic mutations that can significantly increase the risk of developing cancer within 10 years,” she says. “Our results were consistent in two very different groups: persons with known risk factors undergoing cystoscopy and those assumed to be healthy.”
Should the results be replicated in larger cohorts, urine testing for these mutations could allow routine screening of high-risk groups, such as smokers or people exposed to known bladder carcinogens through their work,” she announces.
As he points out, “this type of test could also be used when patients come to the doctor with blood in the urine, to help reduce the unnecessary cystoscopies. If we can identify bladder cancer at an early stage, before the disease has progressed, we can save more lives.”
In the words of the Dr. Joost Boormans, member of the UAE Scientific Congress Bureau and urologist at the Erasmus University Rotterdam Medical Center: “Research of this nature is very encouraging, as it demonstrates that our ability to identify molecular alterations in liquid biopsies such as urine that could indicate the presence of cancer is constantly improving.
“While we need to develop more accurate diagnostics, it is unlikely that in the near future we will have a mass screening program for the bladder cancer. A urine test for genetic mutations could be useful in reducing the number of cystoscopies and scans in patients with bladder cancer who are being followed up for recurrences, as well as those referred for the presence of blood in the urine. A simple urinalysis would be much easier for patients to perform than invasive procedures or scans, as well as being less costly for healthcare services.”