Researchers at the University of Michigan Rogel Cancer Center have created a new urine-based test that aims to solve a significant issue in prostate cancer: distinguishing between the slow-growing type of the disease that is unlikely to cause harm and the more aggressive cancer that requires immediate treatment. The test, called MyProstateScore2.0, or MPS2, analyzes 18 different genes.Different genes have been found to be associated with high-grade prostate cancer. In various tests using urine and tissue samples from men with prostate cancer, it has successfully detected cancers classified as Gleason 3+4=7 or Grade Group 2 (GG2), or higher. These types of cancer 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 impacts. More than one-third of prostate cancer diagnoses are this low-grade form. Gleason and Grade Group are both used to classify how aggressive prostate cancer is.
The results have been published in JAMA Oncology.
“Our current standard test is lacking in terms of accurately identifying these more aggressive forms of prostate cancer,” said lead researcher Dr. Smith.The ability to detect significant cancer has greatly improved over the past twenty years. Previously, the focus was on detecting any type of cancer, but now it is understood that slow-growing cancer may not require treatment. Co-senior study author John T. Wei, M.D., David A. Bloom Professor of Urology at Michigan Medicine, explained that there has been a shift from needing to find any cancer to now focusing on detecting only significant cancer. Prostate-specific antigen (PSA) continues to be crucial in detecting prostate cancer. MPS2 is an advancement of a urine-based test created by the U-M team nearly ten years ago, which followed the discovery of two genes that fuse together.The current MPS test, which is used today, examined PSA, the gene fusion TMPRSS2::ERG, and another marker called PCA3, but it was not as effective in detecting high-grade or clinically significant prostate cancer. Co-senior author Arul M. Chinnaiyan, M.D., Ph.D., director of the Michigan Center for Translational Pathology, stated that there was an unmet need with the existing MyProstateScore test and other commercial tests. The new test is designed to address this need by improving the detection of high-grade or clinically significant prostate cancer. Chinnaiyan’s lab discovered the T2::ERG gene fusion.The initial MPS test was developed by researchers. To improve MyProstateScore’s ability to detect high-grade cancers, scientists used RNA sequencing to identify 54 genes that were uniquely overexpressed in higher-grade cancers out of more than 58,000 genes. These biomarkers were then tested using urine samples from about 700 patients who had undergone a prostate biopsy at U-M between 2008 and 2020 due to elevated PSA levels. This research was part of the National Cancer Institute’s Early Detection Research Network. As a result of this work, 18 markers consistently showed promise.The research found that there is a strong link between MPS2 markers and higher grade disease. The test now includes the original MPS markers as well as 16 additional biomarkers to enhance their effectiveness. The research team then collaborated with the Early Detection Research Network (EDRN), a group of over 30 labs nationwide, to collect a diverse range of samples. U-M team tested over 800 urine samples using MPS2 and sent the results to the NCI-EDRN for evaluation. The results showed that MPS2 is more effective in identifying higher grade diseases.Identifying GG2 or higher cancers. Importantly, it was nearly 100% accurate at ruling out GG1 cancer.
“If you test negative, 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.
Additionally, MPS2 was more effective at helping patients avoid unnecessary biopsies. While 11% of unnecessary biopsies were avoided with PSA testing alone, MPS2 testing could avoid 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 sSkip a biopsy. If a man has previously had a biopsy, the test works even better,” Wei explained.
For instance, a patient might undergo a prostate biopsy because of an elevated PSA, but no cancer is found. The patient is monitored over time and if his PSA increases, he would usually require another biopsy.
“For 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. These are practical applications for patients out there. Nobody wants to say sign me up for another biopsy. We are always looking for alternatives.”Here it is,” Wei stated. MPS2 can be accessed through LynxDx, a company spun off from the University of Michigan with an exclusive license to commercialize MPS2. Patients seeking more information can contact the Michigan Medicine Cancer AnswerLine at 800-865-1125. The primary authors of the paper are Jeffrey J. Tosoian, M.D., M.P.H., now at Vanderbilt University, and Yuping Zhang, Ph.D., and Lanbo Xiao, Ph.D., at U-M. Other contributors include 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.This work was funded by the Michigan-Vanderbilt Early Detection Research Network Biomarker Characterization Center and Data Management and Coordinating Center, which are supported by National Cancer Institute grants U2C CA271854 and U24 CA086368. Additional funding was provided by NCI grants P50 CA18. The authors of this work include 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.6786, R35 CA231996, U24 CA115102, U01 CA113913; Prostate Cancer Foundation; Howard Hughes Medical Institute; and the American Cancer Society.
Chinnaiyan is on 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 an exclusive license from the University of Michigan to commercialize MPS2 and the TMPRSS2-ERG gene fusion. Tosoian and Chinnaiyan are equity holders and scientific advisers to LynxDx. Siddiqui, Zhang, Xiao and Niknafs have served as scientific advisers
