Testing for genetic mutations in urine may help clinicians detect bladder cancer years before the disease shows clinical symptoms, according to new findings presented by Le Calvez-Kelm et al at the 2023 European Association of Urology Annual Congress (Abstract A0268). The researchers identified mutations across 10 genes that were capable of predicting the most common type of bladder cancer up to 12 years in advance of diagnosis.
Background
With over 200,000 cases each year, bladder cancer is one of the most common cancers in the European Union and the UK. Patients diagnosed with advanced disease have a 5-year survival rate of about 50%, largely because of late diagnoses and cancer recurrence. By contrast, if their cancer is detected at an early stage, patients may have a 5-year survival rate of over 80%.
“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,” explained lead study author Florence Le Calvez-Kelm, MSc, PhD, a scientist in the Genetic Cancer Susceptibility group at the International Agency for Research on Cancer.
Study Methods and Results
In the new study, the researchers used the UroAmp test, a general urine test that can identify mutations in 60 genes, to focus on mutations within just 10 genes linked to bladder cancer.
They examined the efficacy of the UroAmp test using urine samples from the Golestan Cohort study—which has tracked the health of more than 50,000 patients for over 10 years. The researchers in the new study tested 29 of the samples from the 40 patients who developed bladder cancer during the 10-year Golestan Cohort study period, along with samples from 98 controls.
Among the 29 samples from patients with bladder cancer, the UroAmp test was able to accurately predict future bladder cancer in 66% (n = 19) of them—even though the urine samples had been taken up to 12 years before clinical diagnosis. Additionally, the UroAmp test was able to predict future bladder cancer in 86% (n = 12/14) of the patients who were diagnosed within 7 years of urine collection. The test was accurately negative in 96% (n = 94/98) controls who would not develop cancer in the future. Among those who received a negative test but did eventually develop bladder cancer, no cancer was diagnosed until at least 6 years after the urine collection.
The UroAmp test was also assessed in additional urine samples taken from 70 patients with bladder cancer and 96 controls prior to a cystoscopy. In contrast with the Golestan Cohort study, some of these samples were provided by patients with cancer on the day they were diagnosed, rather than many years before.
The researchers detected mutations in 71% (n = 50/70) of the urine samples from patients whose tumors were visible during the cystoscopy. Some of these were new diagnoses and others involved cancer recurrence. Mutations were not detected in 94% (n = 90/96) of the patients who received a negative cystoscopy.
Conclusions
“We’ve clearly identified which are the most important acquired genetic mutations that can significantly increase the risk of cancer developing within 10 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,” emphasized Dr. Le Calvez-Kelm. “Should the results be replicated in larger cohorts, urine tests for these mutations could enable routine screenings 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 their 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,” she added.
“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,” highlighted Joost Boormans, MD, PhD, Assistant Professor and Chair of the Department of Urology at the Erasmus University Medical Center Rotterdam and a member of the European Association of Urology Scientific Congress Office. “While we do need to develop more accurate diagnostics, it’s unlikely that we’ll have a mass screening program for bladder cancer in the near future. Whereas, a urine test for genetic mutations could show its value in reducing cystoscopies and scans in [patients with] bladder cancer 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, [and would be] less costly for health services,” he concluded.
The researchers noted that the results of their new study may demonstrate the potential of a genetic urine test to accurately detect bladder cancer at its earlier stages.
Disclosure: For full disclosures of the study authors, visit resource-centre.uroweb.org.
