A new urine test helps doctors distinguish indolent forms of prostate cancer, which rarely cause damage and spread, from more aggressive ones, which must be addressed immediately. The test is based on the examination of 18 different genes related to high-grade prostate cancer and was developed by researchers at the Rogel Cancer Center at the University of Michigan in the USA.
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Active surveillance
A crucial aspect of prostate cancer is the distinction between aggressive tumors and slow-growing ones: the former must be subjected to even radical treatments in a short time (prostatectomy surgery or radiotherapy). The others, however, which are much more frequent, can be monitored over time. This is what is meant by active surveillance. In the study just published on JAMA Oncologythe test – which is called MyProstateScore2 and is currently marketed by a spin-off company from the University of Michigan – has successfully identified prostate tumors as low as GG, or Grade Group 2 (which corresponds to Gleason classification 7). The Gleason score, which today starts from 6 and reaches 10, is assigned by the pathologist with a microscopic analysis of the prostate tissue taken either by biopsy or by surgery.
A tumor with a Gleason score of 6 (or GG 1) is considered potentially non-aggressive, cases with a Gleason score of 7 or higher are classified as high risk or clinically important. “About twenty years ago we looked for any tumor. But since we knew that slow-growing prostate cancer doesn’t need to be treated, suddenly the approach changed. We went from having to look for any cancer, to only looking for tumors significant,” said the study’s co-senior author John Thomas Wei, head of the Division of Andrology and General Urology at the University of Michigan Medical School. Adding that, however, current standard tests do not clearly identify patients with clinically significant cancer.
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The previous test
MyProstateScore2 is a sort of update, so to speak, of MyProstateScore (Mps), a urine test that the same team of researchers had developed almost ten years ago, after the discovery that the fusion of two genes, Tmprss2 and Erg, it is linked to most cases of prostate cancer. In urine samples, Mps looks for Psa (the prostate antigen, which is always central in the diagnosis of the disease), the Tprss2-Erg fusion gene, and another marker called Pca3. “But there was a need not met by the first MyProstateScore or by the other tests on the market today that can detect prostate cancer but generally don’t do a good job of identifying high-grade, or clinically significant, cancer. So, this new test addresses this unmet need,” said the director of the Michigan Center for Translational Pathology and co-senior author of the publication Arul M. Chinnayan (in whose laboratory it has been demonstrated that the fusion of the two genes Tmprss2 and Erg is recurrent in prostate cancer).
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I study
To improve the performance of the first MyProstateScore, and in particular its ability to identify high-grade tumors, the researchers used RNA sequencing of a group of over 58,000 genes, which they then narrowed down to 54: 54 over- expressed specifically in higher grade tumors. Through a series of steps carried out on urine samples from hundreds of patients and thanks to the involvement of theEarly detection research network (EDRN) – a consortium of over 30 laboratories spread across the USA – have finally narrowed the field to 18 markers consistently correlated with high-grade disease. They cross-referenced the results of Mps2 with patient medical records, and thus demonstrated that Mps2 is significantly better than its predecessor in identifying intermediate- or high-risk prostate cancers, and, more importantly, it is capable, in almost 100% of cases, to exclude low-grade disease. “If you are negative on this test it is almost certain that you do not have aggressive prostate cancer,” Chinnaiyan said.
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Biopsies (and second biopsies) are avoidable
That’s why MPS2 can help doctors avoid unnecessary biopsies on patients. According to the studies conducted, while with the PSA test alone 11% of unnecessary biopsies were avoided, with Mps2 41% were avoided. Which means that “four out of 10 men who would have a negative biopsy will have a low-risk MPS2 result – explained Wei – and could avoid it. Furthermore, he added, “a negative MPS2 can avoid half of the men who have already had a biopsy biopsy and were scheduled for another, to undergo the second. These are important practical implications for patients.”
An ethically interesting concept
“It’s an interesting work, this one just published in Jama oncology – says a Oncoline Sergio Bracarda, National President of SIUrO, the Italian Society of Uro-oncology – At this moment – he explains – even patients with a Gleason score of 6 are subjected to a multi-parametric MRI and biopsy. But this work adds a step upstream of these diagnostic steps: the new test could in fact allow only important clinical cases to be ascertained, excluding others, and with a non-invasive method. An ethically interesting concept, given that it reduces the diagnostic burden on healthcare systems, as well as on patients: on those who today carry out invasive tests and who could avoid them, on those who have already had them and should undergo them again. Furthermore, as we will see, this test could be evaluated for the purposes of a possible screening for prostate cancer.”
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– 2024-04-19 10:54:47
