A urine-based test is the very epitome on noninvasive diagnostics, and while this strategy has been employed for various cancers in the past, investigators at UCLA and the University of Toronto think they now may have hit pay dirt. The researchers identified a new biomarker found in urine that can help detect aggressive prostate cancer, potentially saving hundreds of thousands of men each year from undergoing unnecessary surgeries and radiotherapy treatments. Findings from the new study were published recently in JNCI: Journal of the National Cancer Institute through an article titled “Temporal stability and prognostic biomarker potential of the prostate cancer urine transcriptome.”
“We currently do not have accurate biomarkers to help determine the aggressiveness of prostate cancer that is not invasive,” explained senior study investigator Paul Boutros, PhD, director of cancer data science for the UCLA Jonsson Comprehensive Cancer.
Prostate cancer can be easy to diagnose but classifying patients into risk groups have been challenging. Current tools, which include PSA tests and biopsies, have high error rates and can cause severe health complications such as life-threatening infections. Testing for biomarkers in urine is noninvasive and accurately helps to distinguish slow-growing cancers from potentially life-threatening ones.
Under current screening tools, about 25–40% of men are diagnosed with a clinically insignificant disease, meaning the prostate cancer is slow growing and would most likely not have any significant damaging health effects. Yet, these men often still get treated, which leads to major costs for both the individual and the health care system. An additional 20–35% of men with prostate cancer diagnoses don’t get enough treatment, and often suffer a relapse of the disease.
The standard clinical care to determine whether someone has prostate cancer is to undergo a biopsy procedure. A needle is inserted into the prostate and a tiny piece of the prostate tissue, both normal and tumor cells, are removed. But that’s invasive and brings all sorts of clinical risks. Another way to detect prostate cancer is with a blood draw, which is less invasive but not always accurate. The easiest way to evaluate the prostate is to take a sample of the urine since the prostate will always be shedding things into the urine as part of its natural biology, Boutros said.
“We developed a three-stage experimental strategy that would maximize statistical and data science considerations to give us the best chance of finding a biomarker to predict prostate cancer aggressiveness,” said Boutros, who is also a professor of urology and human genetics at the David Geffen School of Medicine at UCLA.
Amazingly, researchers were able to identify a biomarker using the microRNA in urine, which may give physicians insight into how far a tumor has spread and how it may best be treated. These small pieces of RNA that were used to develop the biomarker are involved in prostate cancer development and progression, influence how men respond to treatment, and are detectable in urine, making this detection tool a promising noninvasive option.
“We measured the longitudinal stability of 673 miRNAs by collecting serial urines from 10 patients with localized prostate cancer,” the authors wrote. “We then measured temporally stable miRNAs in an independent training cohort (n = 99) and created a biomarker predictive of Gleason grade using machine-learning techniques. Finally, we validated this biomarker in an independent validation cohort (n = 40).”
To test the noninvasive application, the team worked with 149 men to create and validate a biomarker to show that it works well and could be used to predict the likelihood of aggressive prostate cancer. Participants in the study were evaluated for at least three years, allowing researchers to fully understand how their cancer changed over time.
“Being able to go beyond just a snapshot in time is critical because you are able to focus in on the trends that are associated with the cancer, which is really the most important thing to distinguish in order to develop an accurate biomarker,” Boutros remarked.
The team found the biomarker was successful in identifying high-risk individuals and it achieved similar accuracy as compared with the invasive tissue-based tests. In the study, the test accurately identified 80% of aggressive cancers. The researchers estimate that about 50% of treatments were unnecessary and could have been avoided by using the noninvasive test.
“What this test does is gives the clinician, the patient, and their caregivers confidence in their treatment plan,” Boutros concluded.
