Researchers have found that the new PENK methylation (mePENK) test could potentially pave the way for a breakthrough in early bladder cancer detection in patients with hematuria, according to a novel study published by Oh et al in The Journal of Molecular Diagnostics. The findings could reduce the number of unnecessary invasive cystoscopies and alleviate the economic burden of bladder cancer.
Background
When bladder cancer is detected early, patients have a 5-year survival rate of over 80%; however, this rate declines significantly as the disease progresses to advanced stages, often requires bladder removal, and has a high risk of recurrence. As a result, bladder cancer ranks among the most expensive types of cancers to treat and manage.
One of the most common symptoms of bladder cancer is hematuria—which accounts for up to 20% of all urologic visits. Hematuria is seen in approximately 85% of patients with bladder cancer and 5% to 20% of hematuria cases are diagnosed with bladder cancer. Nonetheless, hematuria is prevalent among adults and may have other causes.
“Diagnosing bladder cancer at an early stage is critical and not only can increase patient survival rates but can also contribute to reducing health-care costs. Current guidelines recommend cystoscopy and imaging examinations for almost all patients presenting with hematuria for initial diagnosis of bladder cancer, but it is invasive, inconvenient, economically burdensome for patients, and frequently fails to detect early-stage bladder cancer. There is therefore an urgent need for a sensitive and precise technique to diagnose early bladder cancer effectively among patients with hematuria,” explained the study authors.
Study Methods and Results
In the new study, the researchers examined the aberrant mePENK biomarker, which has shown a high clinical correlation with bladder cancer in previous studies. The researchers first developed a highly sensitive methylation test for mePENK using urine DNA and evaluating its diagnostic effectiveness among patients with hematuria. The cutoff value for the mePENK test was initially determined in a case-control study involving 175 patients with bladder cancer and 143 patients with benign hematuria. The researchers found that the test exhibited a sensitivity of 86.9% and a specificity of 91.6% when distinguishing bladder cancer from benign hematuria.
The researchers then conducted a subsequent independent prospective clinical performance study comprising 366 patients with hematuria who were scheduled to undergo cystoscopy. They compared the mePENK test results with the cystoscopy findings and histological analysis as the reference standards and identified 38 cases of bladder cancer. The researchers reported that the overall sensitivity of the mePENK test in detecting bladder cancer at all stages was 84.2%, whereas the specificity reached 95.7%. Notably, the test demonstrated a sensitivity of 92.3% in detecting high-grade and advanced-stage bladder cancer.
Conclusions
“Although the [U.S. Food and Drug Administration] has approved several urine biomarker–based products, these methods have not been effectively utilized for early bladder cancer diagnosis. There are some in vitro molecular diagnostic techniques that measure genetic and epigenetic biomarkers for bladder cancer that are undergoing clinical trials, but they have yet to provide sufficient clinical evidence for the initial diagnosis of primary bladder cancer,” stressed co–senior study author Ju Hyun Shin, MD, in the Department of Urology at the Chungnam National University College of Medicine.
“In this study, we used a test based on a single biomarker … to detect primary bladder cancer in [patients with] hematuria and compared its clinical performance with tests that combined multiple biomarkers. Surprisingly, our findings revealed that the mePENK test was equal to or even superior to these multiple biomarker tests. Furthermore, the noninvasive nature of using a urine sample and the simplified test procedure offer advantages such as a shorter turnaround time for sample processing and efficient and accurate analysis of results,” highlighted co–senior study author Sungwhan An, PhD, Chief Executive Officer and Scientific Director of Genomictree. “The results demonstrate high sensitivity and accuracy in detecting bladder cancer. Using void urine as a sample offers significant advantages, ensuring easy accessibility to diagnostic opportunities for patients. The test has the potential to significantly reduce bladder cancer–related deaths and medical expenses. To implement the test in clinical practice larger-scale prospective clinical trials are needed, and we are actively pursuing that goal,” he concluded.
Disclosure: For full disclosures of the study authors, visit jmdjournal.org.
