Individuals who have had bladder cancer in the past are at high risk of recurrence, but researchers publishing in the journal Clinical Cancer Research say a simple DNA methylation marker test in urine can predict tumor recurrence.

The researchers were led by Gangning Liang, PhD, an associate professor in the Department of Urology at the University of Southern California Norris Comprehensive Cancer Center in Los Angeles.

He says that non-muscle-invasive bladder cancer (NMIBC) comprises 80% of all bladder cancer cases. There is a high rate of recurrence with this cancer, which Liang says leads to high treatment costs.

“The current standards for monitoring of bladder cancer recurrence are either unreliable or invasive,” he adds. “We wanted to find reliable biomarkers to monitor recurrence of NMIBC using a noninvasive assay.”

The team focused on DNA methylation, which is the process by which genes can be activated or silenced. Measuring three DNA methylation markers in urine, the test was able to predict tumor recurrence “with high sensitivity and specificity,” the researchers say.

To study the effectiveness of the test, the team collected 368 urine samples over 7 years from 90 NMIBC patients who were being watched for tumor recurrence. After isolating DNA from the samples, they performed DNA methylation analyses and identified six markers.

From this, they shortlisted a three-marker combination – SOX1, IRAK3 and L1-MET – that resulted in the highest specificity, with an area under the curve (AUC) score of 0.95.

The researchers explain that an AUC score of 1 means the test is perfect in anticipating the outcome and scores near 0.5 mean the test is inaccurate.

“In some cancers, patterns of DNA methylation are disturbed, and DNA methylation markers can be early indicators of tumorigenesis and tumor recurrence; they are stable not only in tissues, but also in biological fluids,” Liang says.

Fast facts about bladder cancer

  • Three times as many males than females develop bladder cancer.
  • The rate is twice as high in white people, compared with black or Hispanic people.
  • Most patients are aged 55 years or older at diagnosis.

He adds that the technology they developed “can detect DNA methylation changes in a small amount of DNA in patients’ urine.”

In detail, the researchers found that the test was able to detect tumor recurrence with 80% sensitivity and 97% specificity in the NMIBC patients.

Whereas standard methods of monitoring – cytology and cytoscopy – were only able to detect tumor recurrence in 35% and 15% of cases respectively, the new test predicted tumor recurrence in 80% of the patients who later had a recurrence.

Additionally, 74% of the patients whose urine tests were negative for the markers did not develop a tumor.

Liang notes that their test allows for early detection of recurrence without being invasive. “By routine testing methods, we hope to identify recurrence before the appearance of symptoms, because by the time symptoms appear, the cancer may have already begun to spread,” he says.

Although the test needs to undergo larger clinical trials before it can be used in clinics, Liang adds:

Our findings can be used not only to monitor the recurrence of bladder cancer, but also to monitor response to chemotherapy, and this approach may also be adopted in monitoring recurrent prostate, kidney and lung cancers by noninvasive means.”

In 2013, Medical News Today reported on a study that suggested women can reduce bladder cancer risks by increasing consumption of fruits and vegetables.