Bladder cancer mutations in a specific gene can be detected in the urine up to 10 years before clinical diagnosis of the disease, according to a new study by the World Health Organization (WHO) researchers.
The test is based on detecting mutations in the telomerase reverse transcriptase (TERT) gene – the most common mutations in bladder cancer, according to the report conducted by WHO’s International Agency for Research on Cancer (IARC) and international partners.
The new evidence is detailed in an article published by The Lancet on Feb 17, which highlights the potential of early detection through a simple urine DNA test.
“A simple urine test has recently been developed, and these new results are another exciting step towards the validation of a non-invasive early detection tool,” said Florence Le Calvez-Kelm, IARC scientist and principal investigator of the study.
“This test could significantly improve and simplify the way in which bladder cancer is detected.”
Bladder cancer is where a growth of abnormal tissue develops in the bladder lining. In some cases, the tumour spreads into the bladder muscle. The most common symptom of bladder cancer is blood in urine, which is usually painless.
In 2018, an estimated 549,000 people were diagnosed with bladder cancer and 200,000 of them died from it. Bangladesh has an estimated 1.5 million cancer patients. Of them, approximately 150,000 die every year.
IARC data showed that the country recorded 150,781 new cancer cases and 108,137 deaths in 2018. Of the new cases, 1,626 were bladder cancer cases while 992 people died from it that year.
Researchers said the absence of appropriate and reliable screening methods, the invasiveness of diagnostic modalities and high recurrence rates (50–70 percent) after the initial treatment make it one of the most challenging and expensive cancers to diagnose and treat.
Early detection could significantly contribute to reducing mortality, morbidity and economic burden of bladder cancer, they said.
Urine tests are not currently recommended by urological societies because there is a lack of evidence on early detection efficiency, relegating the diagnosis of bladder cancer to relying largely on invasive and expensive procedures like cystoscopy.
Researchers said the ability to detect these mutations in pre-diagnostic urine samples has enormous possibility as a non-invasive tool for early detection and may also offer potentially cost-effective screening of high-risk individuals.
To assess the test’s ability to detect mutations in urine samples before any clinical symptoms of bladder cancer occur, IARC researchers collaborated with the Tehran University of Medical Sciences in Iran and the United States National Cancer Institute to design a pilot study within the Golestan Cohort Study.
Researchers performed a nested case-control study within the population-based prospective Golestan Cohort Study of 50,045 participants (aged 40-75) and followed up to 14 years.
Their evaluation of the performance of TERT promoter mutations as early detection biomarkers for bladder cancer in urine samples revealed detection in 46.7 percent of the asymptomatic individuals who later developed bladder cancer.
This was up to 10 years before being clinically diagnosed.
Ismail Hosen, co-first author of the study, said that the results provide the first evidence from a prospective population-based cohort study of the potential of urinary TERT promoter mutations as promising non-invasive biomarkers for the early detection of bladder cancer.
“The Golestan Cohort Study is one of the few prospective population-based cohorts that provide the opportunity to assess urinary biomarkers for the pre-clinical detection of bladder cancer,” said Professor Reza Malekzadeh, the principal investigator of the Golestan Cohort Study and a co-senior author of the article.
IARC scientists are now collaborating with other large prospective cohort studies to confirm these findings.
“If the findings are validated, large trials conducted in individuals at high risk of developing bladder cancer should be designed to address the health and cost benefits of screening for TERT promoter mutations for the global bladder cancer burden,” said Mahdi Sheikh, a postdoctoral scientist at IARC and the co-first author of the study.