According to the American Cancer Society (ACS), about 84,870 new cases of bladder cancer (about 65,080 in men and 19,790 in women) will be diagnosed in the US in 2025. Approximately 75% of the patients will present with non-muscle invasive bladder cancer (NMIBC), generally carrying a good prognosis, with a 5-year cancer-specific survival close to 90%. Despite a favorable prognosis, there is a risk of recurrence and progression to muscle-invasive bladder cancer (MIBC), where survival drops to 35%. High-risk patients with the most aggressive type of bladder cancer have a 60% to 70% likelihood of cancer recurrence within 5 years after surgery, which is why postsurgical follow-up among these patients is often intensive. Cystoscopy is the gold standard for surveillance of non-muscle invasive bladder cancer (NMIBC), but the procedure is invasive, uncomfortable, and costly. Also, the sensitivity is suboptimal, and particularly carcinoma in situ (CIS) is easily overlooked. There is a need for a noninvasive test for the accurate detection of bladder cancer recurrences, with the potential to reduce the number of cystoscopies, and with the ability to guide and improve patient care.
Two research studies with a longitudinal design followed bladder cancer patients for 2 years:
Researchers from the Department of Molecular Oncology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Norway, investigated the potential of analyzing urine samples for the presence of urine tumor DNA (utDNA) (1) to replace cystoscopy for surveillance of bladder cancer recurrence. Residual cancer cells after surgery, often referred to as minimal residual disease (MRD), represent a clinical challenge in many cancer types, including NMIBC. MRD can eventually lead to recurrence and is typically difficult to detect with existing diagnostic tools. In their study, repeated analysis of utDNA at each cystoscopy control detected cancer recurrences with high sensitivity across all stages and grades. In almost half of the cases, the recurrence was detected earlier with utDNA than with cystoscopy. utDNA analysis detected both high and low-grade lesions with almost 90% sensitivity, Ta recurrences with 83% sensitivity and T1-T2 and CIS recurrences with 100% sensitivity. In addition, utDNA analysis returned < 1% false negative test results, and showed the potential to reduce the number of cystoscopies by 55%, benefitting almost 80% of the patients.
Researchers at the Bladder Cancer Research Team in the Department of Urology at Aarhus University Hospital in Denmark, have found that a novel urine biomarker test called Xpert Bladder Cancer Monitor (2) may effectively halve the number of cystoscopies necessary in high-risk patients with bladder cancer. The research also reported no increased risk of recurrence in patients who underwent a urine biomarker test rather than a standard flexible cystoscopy. Thomas Dreyer, MD, PhD, presented the research findings at the European Association of Urology (EAU) Congress last year. He expressed confidence that the test was sensitive enough not to provide false-negatives that would put patients at risk or provide false-positives requiring an equal or even higher numbers of cystoscopies being carried out.
The researchers randomly assigned 313 high-risk patients with bladder cancer to undergo either the standard three cystoscopies per year or one cystoscopy followed by two urine biomarker tests per year. The novel urine biomarker test was designed to monitor for bladder cancer recurrence by measuring levels of five target mRNAs. The patients who received positive results were called into the hospital for a cystoscopy to check for evidence of cancer recurrence. The urologists performing the cystoscopies were aware of the positive results.
After 2 years, 44% of the follow-up appointments among patients in the urine biomarker test group involved a cystoscopy compared with nearly 100% among those in the standard-treatment group. Additionally, the researchers found evidence that the urine biomarker tests were capable of detecting cancer recurrence before any disease was visible through the cystoscopy. Among more than 50% of the patients who had false-positive test results, there was evidence of cancer recurrence at a later appointment.
Bladder cancer is a disease that particularly affects the elderly, and we can foresee an increasing number of patients due to the aging population. These two trials show us a possible means of reducing cystoscopies. “If given the option of providing a urine sample instead of undergoing an uncomfortable medical procedure, most patients would choose that, so long as they were confident it was just as effective,” added Dr. Dreyer.
