At-Home Urine Test for Prostate Cancer Shows Promise
Levels of potential biomarkers for prostate cancer in urine were comparable after a digital rectal examination (DRE) in a physician’s office and at a man’s home, suggesting the feasibility of an at-home test, say UK researchers in a small preliminary study.
“Historically, patient urine samples have been collected after a digital rectal examination of the prostate, which was thought necessary to boost the levels of prostatic secretions in the urine,” explain the authors, led by Jeremy Clark, PhD, Norwich Medical School, University of East Anglia, UK.
But among 14 British men in the study, an at-home collection protocol provided RNA quantity and quality on par with post-DRE collection in a medical office setting.
The protocol employs a commercial preservative, which allows room temperature storage without loss of RNA quality, and a vacuum extraction method that increases RNA yields and provides other benefits.
The results were published online November 29 in BioTechniques.
However, the new commercial protocol is a long way away from use because the biomarkers used in the study are not clinically validated, said an expert not involved with the study.
“These urine-based biomarkers, although promising and an area of active research, are not yet recommended for prostate cancer screening or during management of prostate cancer by active surveillance. Therefore, these findings do not currently have any clinical or public health implications,” said Mangesh Thorat, MBBS, deputy director, Cancer Prevention Trials Unit, King’s College London, UK.
Nonetheless, lead author Clark speculated that the at-home test “could in future revolutionize how those on ‘active surveillance’ are monitored for disease progression, with men only having to visit the clinic for a positive urine result.”
He further commented: “This is in contrast to the current situation where men are recalled to the clinic every 6 to 12 months for painful and expensive biopsies.”
Based on previous studies in samples collected post-DRE, the test could predict whether patients will require treatment “up to 5 years earlier than standard clinical methods,” Clark said.
“It means that a negative test could enable men to only be retested every 2 to 3 years, relieving stress for the patient and reducing hospital workload,” he added.
Co-author Robert Mills, MD, a consultant surgeon at Norfolk & Norwich University Hospitals NHS Foundation Trust, UK, said the study is “a very exciting development.”
The test may allow differentiation of men who do and do not have prostate cancer and avoid “putting a lot of men through unnecessary investigations,” which he described as “invaluable.”
The management of prostate cancer, which is diagnosed in almost half of men aged over 60 years, is complicated by only a small proportion of patients eventually dying from the disease.
To try to identify those patients and take into account the heterogeneity and multifocality of the tumors within the prostate, researchers previously examined tumor secretions found in the urine.
They previously found that those secretions, which carry cancer cells and cell-free RNA (cfRNA), can be used to detect clinically significant prostate tumors with a pathological Gleason score ≥ 7.
A study published by the team earlier this year indicated that a four-marker prostate urine risk signature in just one sample was able to predict progression in active surveillance patients up to 5 years later at a hazard ratio of 8.23.
Clark told Medscape Medical News that those samples were collected following DRE, which is a routine examination, and “was thought to be necessary to push secretions from the prostate into the urethra, so they’d be then flushed out with the urine.”
However, he explained that there were “problems,” as “men don’t like it” and clinicians with relatively short fingers “don’t reach the prostate properly.”
Therefore, results were inconsistent, with RNA yields per sample “aligned to which clinician had performed the DRE, so it was having a huge knock-on effect on the amount of cancer markers we were detecting in the urine.”
Looking to improve the technique, Clark said the team “found some really old papers” that showed the prostate was “constantly secreting, so I thought, well, why don’t we try it first thing in the morning, at home, without a DRE and…that would give us much better amounts of cancer markers.”
The current study was funded by the Movember Foundation GAP1 Urine Biomarker project, Masonic Charitable Foundation, Bob Champion Cancer Trust, King family, Andy Ripley Memorial Fund, and Stephen Hargrave Trust.
To examine the effectiveness of an at-home urine collection system, the researchers studied men attending urology clinics at a single hospital who had urine samples taken before or at least 3 months after biopsy.
The men were provided with the at-home urine sample kits and a leakproof container with pre-paid postage, all of whom sent back the kits within 3 days of sample collection.
In all, 14 men provided a post-DRE urine sample, a sample of the first micturition of the day (H0), and a sample taken 1 hour later (H1).
cfRNA yields were comparable across the three samples.
Reverse transcription polymerase chain reaction (PCR) revealed that, although KLK2 and PCA3 transcript yields were comparable, TMPRSS2:ERG was detectable in eight at-home samples but only three post-DRE clinic samples (P = .12).
The team found that overall median PCR yields were 11%–33% higher in H0 than in H1 samples, leading them to suggest a minimum of 2 to 3 hours may be needed for transcription levels to reach those in H0 samples.
As the effect of ejaculation is also unclear, they believe it may be necessary for a patient to wait 24 hours after sexual activity before providing a sample.
Following the direct comparison between at-home and post-DRE samples, the team has stopped taking urine samples post-DRE and has now collected around 150 at-home samples.
Clark explained they have received funding to conduct a validation study and will be collecting samples from patients at four hospitals in the UK, as well as at sites across Europe, the United States, and Canada.
With the validation study expected to take 3 years, Clark said, “hopefully, within 3 to 5 years we should have something that could be used in the hospital.”
Justin Stebbing, MD, PhD, professor of cancer medicine and medical oncology, Imperial College, London, UK, who was not involved in the research, commented in a release: “The use of home tests which empower the consumer or patient are going to be very important in years to come.”
However, he cautioned: “How we incorporate these into clinical care pathways will require a great deal of work, not least of all establishing how these tests improve outcomes.”
“A test that can replace a hospital or doctor-based examination is important, but this study is too small right now to draw any conclusions but can provide the basis of future clinical testing in a study to evaluate these questions,” he said.