Scientists develop a new method for diagnosing prostate cancer – a urine test that can be done in the comfort of your own home.
Prostate cancer is the most common (none skin) cancer diagnosed in men in the United States. These cancers are slow-growing making them difficult to treat, constant assessment and monitoring is required to detect when they become aggressive. Early detection of prostate cancer is based on a blood test that detects prostate-specific antigen (PSA) in combination with a digital rectal examination (DRE). Biopsies of the prostate are then taken to confirm a diagnosis. This is done using a technique called transrectal ultrasound-guided biopsy. None of these diagnostic tools are particularly comfortable for the patient to endure. As prostate cancers are slow-growing and PSA blood tests and DRE are required every 3-6 months to check on disease progression.
The trouble with the PSA blood tests is that PSA is not particularly specific as a marker for prostate cancer. High levels of PSA can also be caused by large prostate volume, benign prostate hyperplasia, or prostatitis (swelling of the prostate). This has caused a high false-positive rate leading to overdiagnosis and subsequent overtreatment of patients. This exposes many men unnecessarily to the unwanted side effects of treatments such as sexual impotence, urinary incontinence, and bowel problems. The current diagnostic approach is not suitable for early detection and monitoring of disease progression in prostate cancer.
There are currently a variety of none invasive diagnostic tests in development for the detection of prostate cancer. Many of which focus on using small molecules found in bodily fluids called biomarkers. These molecules are secreted specifically by cancer cells and can include DNA, RNA, and various proteins. Urine is an ideal body fluid to use to screen for the presence of these biomarkers. The urethra runs from the bladder through the prostate to the penis, meaning urine is likely to contain sufficient amounts of the cancer-specific biomarkers for analysis and diagnosis. Urine is easy to collect, none invasive, and is harmless to the human body making it an ideal candidate for diagnostic applications. Some examples of urine tests include prostate cancer antigen 3 (PCA3), ExoDx Prostate Intelliscore, and SelectMDx. PCA3 is already commercially available and has regulatory approval. The trouble with most of these tests is they all require digital massage (DRE) of the prostate before urine samples are collected.
In a recent study published in BioTechniques, researchers in the UK wanted to develop a method of diagnosing prostate cancer that could be done at home without the need for prostate massage. The researchers investigated two separate ways of isolating RNA from urine samples. The first was a method called MicroF which used a micro-sieving technique and the second was a technique called Hive which used a novel high volume vacuum extraction method. They found that Hive produced higher yields of RNA for analysis in both frozen and fresh samples. The researchers decided to use Hive processing for subsequent urine samples.
The team then went on to determine if using preservatives in their protocol would help to stabilise RNA at room temperature. They compared Hologic (which is used in PCA3 tests) and Norgen. They found that Norgen worked more effectively to prevent RNA degradation after six months of storage. The scientists coated the sample collection tubes in dried Norgen to ensure samples would remain stable.
The scientists recruited fourteen men to collect urine samples at home. The participants were provided with a kit and instructions on sample collection. The scientists were concerned that they wouldn’t be able to detect the biomarkers in the absence of a prostate massage so they asked the participants to collect urine under three different conditions. One post-DRE urine sample was collected in the clinic and two samples were collected at home. The samples collected at home had to be the first urination of the day and the second was collected an hour later. The scientists then analysed the urine samples for the presence of RNA for three specific genes. They looked at KLK3, which is a prostate-specific transcript (it encodes the PSA protein). They looked at PCA and TMPRSS2:ERG expression both of which are overexpressed in prostate cancer. The researchers found that the yield of RNA was similar for the home kit and the post-DRE samples. There had improved yields for the TMPRSS2:ERG with the home kit.
The scientists showed that this at-home diagnostic tool could be practical and feasible. The protocol presented here does require further validation however, the expression of the three genes together should be correlated with patient outcomes and disease progression. It would also be important to compare this method with standardised tests to determine if the specificity and selectivity is comparable. It would be interesting to know how the expression of these three genes changes during disease progression and if this method can be used to track cancer development and response to treatment.
Written by Tarryn Bourhill Msc, PhD Candidate
References:
- Hendriks, R., Van Oort, I. & Schalken, J. Blood-based and urinary prostate cancer biomarkers: a review and comparison of novel biomarkers for detection and treatment decisions. Prostate cancer and prostatic diseases 20, 12 (2017).
- Wu, D. et al. Urinary biomarkers in prostate cancer detection and monitoring progression. Critical reviews in oncology/hematology 118, 15-26 (2017).
- Simoes, G. F., Sakuramoto, P., dos Santos, C. B., Furlan, N. K. C. & Augusto, T. M. in Pathophysiology-Altered Physiological States (IntechOpen, 2018).
- Litwin, M. S. & Tan, H.-J. The diagnosis and treatment of prostate cancer: a review. Jama 317, 2532-2542 (2017).
- Webb, M. et al. Methodology for the At-Home Collection of Urine Samples for Prostate Cancer Detection. Biotechniques (2019).
