University of Michigan researchers have introduced a urine-based test called MPS2 that can identify aggressive prostate cancers and reduce unnecessary biopsies, which improves how prostate cancer is managed.
A new urine-based test examines 18 genes and was specifically created to distinguish the aggressive cancers requiring immediate treatment from the slow-growing type.
Researchers at the University of Michigan Rogel Cancer Center have developed a new urine-based test to solve a major problem in prostate cancer: how to differentiate the slow-growing form of the disease, unlikely to cause harm, from the more aggressive cancer that requires immediate treatment.
The test, known as MyProstateScore2.0 or MPS2, analyzes 18 different genes associated with high-grade prostate cancer. In various tests using urine and tissue samples from men with prostate cancer, it successfully identified cancers classified as Gleason 3+4=7 or Grade Group 2 (GG2), or higher. These cancers are more likely to grow and spread compared to Gleason 6 or Grade Group 1 prostate cancers, which are unlikely to spread or cause other impact. Over one-third of prostate cancer diagnoses are of this low-grade form.
Gleason and Grade Group are both used to categorize the aggressiveness of prostate cancer.
Results are published today (April 18) in JAMA Oncology.
Evolution of Prostate Cancer Testing
“Our standard test is lacking in its ability to clearly distinguish those with significant cancer. Twenty years ago, we were seeking any kind of cancer. Now we understand that slow-growing cancer does not need treatment. Suddenly, the situation changed. We went from having to find any cancer to only finding significant cancer,” explained co-senior study author John T. Wei, M.D., David A. Bloom Professor of Urology at Michigan Medicine.
The main test for prostate cancer detection remains prostate-specific antigen, or PSA. MPS2 represents an improvement on a urine-based test created by the same U-M team nearly ten years ago, following a landmark discovery of two genes that combine to cause prostate cancer. The original MPS test, still in use today, examined PSA, the gene fusion TMPRSS2::ERG, and another marker called PCA3.
Development of MPS2
“There was still an unmet need with the MyProstateScore test and other commercially available tests. They detected prostate cancer, but in general, they were not as effective at detecting high-grade or clinically significant prostate cancer. The reason for this new test is to address this unmet need,” explained co-senior author Arul M. Chinnaiyan, M.D., Ph.D., director of the Michigan Center for Translational Pathology. Chinnaiyan’s laboratory identified the T2::ERG gene fusion and created the initial MPS test.
To enhance the ability of MyProstateScore to identify high-grade cancers, researchers used RNA sequencing of over 58,000 genes and narrowed it down to 54 unique candidates overexpressed specifically in higher-grade cancers. They tested the biomarkers on urine samples collected and stored at U-M through another major study, the National Cancer Institute’s Early Detection Research Network. This included about 700 patients from 2008-2020 who underwent a prostate biopsy due to an elevated PSA level.
The initial step reduced the number to 18 markers consistently linked to more severe disease. The test still uses the original MPS markers, plus 16 more biomarkers to support them.
Testing and Validation of MPS2
After that, the team contacted the larger Early Detection Research Network (EDRN), a group of over 30 labs nationwide collecting similar samples. This ensured a varied, national sampling. Without specific sample details, the U-M team conducted MPS2 testing on over 800 urine samples and shared results with collaborators at the NCI-EDRN. The NCI-EDRN team evaluated MPS2 results against patient records.
MPS2 proved to be more effective at identifying GG2 or higher cancers. More importantly, it was almost 100% accurate at ruling out GG1 cancer.
“If you’re negative on this test, it’s almost certain that you don’t have aggressive prostate cancer,” said Chinnaiyan, S. P. Hicks Endowed Professor of Pathology and professor of urology at Michigan Medicine.
Impact on Patient Care
Furthermore, MPS2 was better at assisting patients in avoiding unnecessary biopsies. While 11% of unnecessary biopsies were avoided with PSA testing alone, MPS2 testing would avoid up to 41% of unnecessary biopsies.
“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 better,” Wei explained.
For example, a patient may get a prostate biopsy due to an elevated PSA, but no cancer is detected. The patient is followed over time and if his PSA inches up, he would typically need another biopsy.
“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,” Wei said.
MPS2 is currently available through LynxDx, which is University of Michigan spin-off company that has an exclusive license from the university to commercialize MPS2. Patients interested in learning more can call the Michigan Medicine Cancer AnswerLine at 800-865-1125.
Reference: “Development and Validation of an 18-Gene Urine Test for Clinically Significant Prostate Cancer” 18 April 2024, JAMA Oncology.
DOI: 10.1001/jamaoncol.2024.0455
The paper’s first authors are Jeffrey J. Tosoian, M.D., M.P.H., who is now at Vanderbilt University, and Yuping Zhang, Ph.D., and Lanbo Xiao, Ph.D., at U-M. Additional authors are Cassie Xie; Nathan L. Samora, M.D.; Yashar S. Niknafs, Ph.D.; Zoey Chopra; Javed Siddiqui; Heng Zheng, M.D.; Grace Herron; Neil Vaishampayan; Hunter S. Robinson, M.D.; Kumaran Arivoli; Bruce J. Trock, Ph.D.; Ashley E. Ross, M.D., Ph.D.; Todd M. Morgan, M.D.; Ganesh S. Palapattu, M.D.; Simpa S. Salami, M.D., M.P.H.; Lakshmi P. Kunju, M.D.; Scott A. Tomlins, M.D., Ph.D.; Lori J. Sokoll, Ph.D.; Daniel W. Chan, Ph.D.; Sudhir Srivastava, Ph.D.; Ziding Feng, Ph.D.; Martin G. Sanda, M.D.; Yingye Zheng, Ph.D.
Funding for this project comes from the Michigan-Vanderbilt Early Detection Research Network Biomarker Characterization Center and Data Management and Coordinating Center, which are funded by the National Cancer Institute through grants U2C CA271854 and U24 CA086368. Additional funding is provided by NCI grants P50 CA186786, R35 CA231996, U24 CA115102, U01 CA113913; Prostate Cancer Foundation; Howard Hughes Medical Institute; and the American Cancer Society.
Chinnaiyan is part of the advisory boards of Tempus, LynxDx, Ascentage Pharmaceuticals, Medsyn therapeutics, Esanik, and RAAPTA therapeutics. Tomlins is an equity holder and chief medical officer of Strata Oncology. LynxDx has acquired an exclusive license from the University of Michigan to commercialize MPS2 and the TMPRSS2-ERG gene fusion. Tosoian and Chinnaiyan have equity stakes and serve as scientific advisers to LynxDx. Siddiqui, Zhang, Xiao, and Niknafs have also been scientific advisers to LynxDx.
