A novel urine-based test created by researchers at the University of Michigan Health Rogel Cancer Centre tackles a significant issue with prostate cancer. how to distinguish between more aggressive cancer that requires prompt treatment and the slow-growing type of illness that is unlikely to cause harm.
The test, known as MyProstateScore2.0, or MPS2, examines eighteen distinct genes associated with advanced prostate cancer. Using tissue and urine samples from males diagnosed with prostate cancer, it was able to successfully identify tumours categorised as Grade Group 2 (GG2) or above in several tests. Compared to Gleason 6 or Grade Group 1 prostate tumours, which are unlikely to spread or have any adverse effects, these malignancies have a higher propensity to develop and spread. This low-grade type of prostate cancer accounts for around one-third of all diagnoses. Two methods are used to categorise prostate cancer aggressiveness: Gleason and Grade Group.
The findings were published in the journal JAMA Oncology.
Our standard test is lacking in terms of its ability to clearly pick out those who have significant cancer. Twenty years ago, we were looking for any kind of cancer. Now we realize that slow growing cancer doesn’t need to be treated. All of a sudden, the game changed. We went from having to find any cancer to finding only significant cancer.
John T. Wei, M.D., David A. Bloom Professor of Urology at Michigan Medicine.
PSA, or prostate-specific antigen, continues to be the key to diagnosing prostate cancer. The same U-M researchers created a urine-based test over ten years ago, but MPS2 builds upon it when they discovered two genes that merge to produce prostate cancer. The current version of the MPS test examined PSA, the gene fusion TMPRSS2::ERG, and an additional marker known as PCA3.
There was still an unmet need with the MyProstateScore test and other commercial tests currently available. They were detecting prostate cancer, but in general they were not doing as good a job in detecting high grade or clinically significant prostate cancer. The impetus for this new test is to address this unmet need.
Arul M. Chinnaiyan, M.D., Ph.D., director of the Michigan Center for Translational Pathology
To further enhance MyProstateScore’s ability to detect high-grade malignancies, scientists employed RNA sequencing to reduce the pool of more than 58,000 genes to 54 candidates that were found to be specifically overexpressed in higher-grade tumours. Through the National Cancer Institute’s Early Detection Research Network, another significant project, they analysed the biomarkers against urine samples that were gathered and kept at U-M. Approximately 700 individuals between 2008 and 2020 underwent a prostate biopsy as a result of having a high PSA level.
After this initial stage, the number of markers that corresponded consistently with higher-grade illness was reduced to 18. The test still uses the 16 supplementary biomarkers in addition to the original MPS markers.
After that, the group got in touch with the bigger Early Detection Research Network (EDRN), which is a network of over 30 labs nationwide that share a similar sample collection process. This guaranteed a nationwide, diversified sample. The U-M researchers tested more than 800 urine samples for MPS2 without any particular information about the samples, and they transmitted the results to partners at the NCI-EDRN. Assessing MPS2 findings against patient data was done by the NCI-EDRN team.
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Twenty years ago, we were looking for any kind of cancer. Now we realize that slow-growing cancer doesn’t need to be treated. All of a sudden, the game changed. We went from having to find any cancer to finding only significant cancer.
John T. Wei
It was demonstrated that MPS2 is more adept in detecting GG2 or higher malignancies. More significantly, it excluded GG1 cancer almost entirely correctly.
If you’re negative on this test, it’s almost certain that you don’t have aggressive prostate cancer.
Arul M. Chinnaiyan
Additionally, MPS2 was more successful in assisting patients in avoiding pointless biopsies. While MPS2 testing might prevent up to 41% of inappropriate biopsies, PSA testing alone was only able to prevent 11% of unnecessary biopsies.
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Four of 10 men who would have a negative biopsy will have a low risk MPS2 result and can confidently skip a biopsy. If a man has had a biopsy before, the test works even bette.
In those men who have had a biopsy before and are being considered for another biopsy, MPS2 will identify half of those whose repeat biopsy would be negative. Those are practical applications for patients out there. Nobody wants to say sign me up for another biopsy. We are always looking for alternatives and this is it
John T. Wei
Source: Michigan Medicine
Journal Reference: Tosoian JJ, Zhang Y, Xiao L, et al. Development and Validation of an 18-Gene Urine Test for High-Grade Prostate Cancer. JAMA Oncol. Published online April 18, 2024. doi:10.1001/jamaoncol.2024.0455
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