Researchers at the University of Michigan Rogel Cancer Center have developed a new urine-based test that addresses a major problem in prostate cancer: how to separate the slow-growing form of the disease that is unlikely to cause harm from the more aggressive cancer that needs immediate treatment.
The test, called MyProstateScore2.0 or MPS2, analyzes 18 different genes linked to high-grade prostate cancer. In multiple 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. More than a third of prostate cancer diagnoses are thus low-grade. Gleason and Grade Group are used to classify how aggressive prostate cancer is.
The results are published in JAMA Oncology.
“Our standard test lacks the ability to clearly detect those who have a major cancer. Twenty years ago we looked for any type of cancer. Now we realize that slow-growing cancer does not need treatment. Suddenly, the game changed. We passed from having to find any cancer to finding only significant cancer,” said the study’s co-senior author, John T. Wei, MD, David A. Bloom Professor of Urology at Michigan Medicine.
Prostate-specific antigen, or PSA, remains the centerpiece of prostate cancer screening. MPS2 improves on a urine test developed by the same UM team nearly a decade ago, following a landmark discovery of two genes that fuse to cause prostate cancer. The original MPS test, which is used today, looked at PSA, the TMPRSS2::ERG gene fusion, and another marker called PCA3.
“There was still an unmet need with the MyProstateScore test and other commercial tests currently available. They detected prostate cancer, but overall they were not doing a good job of detecting high-grade or clinically significant prostate cancer. The impetus for this The new test aims to address this unmet need,” said co-senior author Arul M. Chinnaiyan, M.D., Ph.D., director of the Michigan Center for Translational Pathology. Chinnaiyan’s laboratory discovered the T2::ERG gene fusion and developed the initial MPS test.
To make MyProstateScore even more effective at identifying high-grade cancers, the researchers used RNA sequencing of more than 58,000 genes and narrowed it down to 54 candidates specifically overexpressed in high-grade cancers. They tested the biomarkers with urine samples collected and stored at UM through another major study, the National Cancer Institute Early Detection Research Network. This included around 700 patients between 2008 and 2020 who came for a prostate biopsy due to an elevated PSA level.
This first step narrowed the field to 18 markers that consistently correlated with higher-grade diseases. The test still includes the original MPS markers, plus 16 additional biomarkers to complement them.
From there, the team reached out to the Early Detection Research Network (EDRN), a consortium of more than 30 laboratories across the country that are also collecting samples. This ensured a diverse national sample. Not knowing specific details about the samples, the UM team performed MPS2 tests on more than 800 urine samples and sent the results to NCI-EDRN collaborators. The NCI-EDRN team evaluated the MPS2 results by comparing them to patient records.
MPS2 was shown to be better at identifying GG2 or higher cancers. More importantly, he was almost 100% correct in ruling out GG1 cancer.
“If you get a negative result on this test, you almost certainly do not have aggressive prostate cancer,” said Chinnaiyan, SP Hicks Professor of Pathology and Professor of Urology at Michigan Medicine.
Additionally, MPS2 was more effective in helping patients avoid unnecessary biopsies. While 11% of unnecessary biopsies were prevented by the PSA test alone, the MPS2 test would prevent up to 41% of unnecessary biopsies.
“Four out 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,” he explained. Wei.
For example, a patient may have a prostate biopsy due to an elevated PSA, but no cancer is detected. The patient is followed over time, and if her PSA increases slowly, she will usually 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. No one wants to tell me to sign up for another biopsy.” “We are always looking for alternatives and this is it,” Wei said.
MPS2 is currently available through LynxDx, which is a spin-off company from the University of Michigan 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.
The paper’s first authors are Jeffrey J. Tosoian, MD, MPH, now at Vanderbilt University, and Yuping Zhang, Ph.D., and Lanbo Xiao, Ph.D., at UM. Additional authors are Cassie Xie; Nathan L. Samora, MD; Yashar S. Niknafs, Ph.D.; Zoey Chopra Javed Siddiqui; Heng Zheng, MD; Grace Herrón; Neil Vaishampayan; Hunter S. Robinson, MD; Kumaran Arivoli; Bruce J. Trock, Ph.D.; Ashley E. Ross, M.D., Ph.D.; Todd M. Morgan, MD; Ganesh S. Palapattu, MD; Simpa S. Salami, MD, MPH; Lakshmi P. Kunju, MD; 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, MD; Yingye Zheng, Ph.D.
Funding for this work comes from the Michigan-Vanderbilt Early Detection Research Network Biomarker Characterization Center and the Data Management and Coordination Center, which are provided through National Institute grants U2C CA271854 and U24 CA086368. of Cancer. Additional funding comes from NCI grants P50 CA186786, R35 CA231996, U24 CA115102, U01 CA113913; Prostate Cancer Foundation; Howard Hughes Medical Institute; and the American Cancer Society.
Disclosures: Chinnaiyan serves on the advisory boards of Tempus, LynxDx, Ascentage Pharmaceuticals, Medsyn therapeutics, Esanik and RAAPTA therapeutics. Tomlins is a shareholder and chief medical officer of Strata Oncology. LynxDx has obtained an exclusive license from the University of Michigan to commercialize MPS2 and the TMPRSS2-ERG gene fusion. Tosoian and Chinnaiyan are shareholders and scientific advisors to LynxDx. Siddiqui, Zhang, Xiao and Niknafs have served as scientific advisors to LynxDx.