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Multigene Urine Test for High-Grade Prostate Cancer Validated in Clinical Study

NEW YORK – A team led by researchers at the University of Michigan has developed and clinically validated an 18-gene urinary test for detecting high-grade prostate cancer.

Detailed in a paper published Thursday in JAMA Oncology, the test is intended to evaluate men with elevated prostate-specific antigen (PSA) levels to help determine if they are at risk for aggressive prostate cancer and therefore require additional follow-up procedures like biopsies or imaging.

In the study, the researchers compared the test's performance to that of other commonly used prostate cancer reflex tests and found that it had higher diagnostic accuracy, allowing it to reduce unnecessary biopsies while maintaining high sensitivity for detecting high-grade cancers.

While PSA testing is commonly used to screen men for prostate cancer, it suffers from a lack of specificity, both for prostate cancer itself and for high-grade prostate cancer requiring quick treatment. Given this, much research has been put toward the development of tests that can assess whether an individual with a high PSA score is likely to have an aggressive cancer.

As the study authors noted, currently the National Comprehensive Cancer Network (NCCN) guidelines include six blood- or urine-based PSA reflex tests. However, they wrote, these tests are typically composed of a small number of markers, which fail to capture the range of pathways involved in aggressive disease. Additionally, the markers used are often not specific for high-grade cancers.

To improve upon existing tests, the Michigan researchers set out to identify markers specific to high-grade prostate cancer, using transcriptomic data to identify genes overexpressed only in high-grade tumors. They then used multiplex PCR to evaluate 54 candidate markers, from which they built an 18-gene panel, which they called MyProstateScore 2.0, or MPS2, a next-generation version of the original two-gene MyProstateScore (MPS) developed by the same research group in 2016.

Both the MPS and MPS2 assays are commercially available from diagnostic firm LynxDx, which was founded by Arul Chinnaiyan, director of the Michigan Center for Translational Pathology, senior author on the JAMA Oncology paper, and a lead developer of the tests.

To develop the 18-gene signature, the researchers used a cohort of 761 men with a median age of 63 and a median PSA level of 5.6 ng/mL. In addition to the 18 genes selected, the model includes the clinical factors of age, race, digital rectal examination findings, PSA level, family history of prostate cancer, and prior negative biopsy. They also developed a separate model called MPS2+ that included prostate volume when a volume measurement is available.

They validated the MSP2 and MPS2+ models in a 743-subject cohort drawn from individuals participating in the National Cancer Institute Early Detection Research Network's prospective PCA3 trial, which has enrolled men at 11 academic centers who have been scheduled for prostate biopsy.

Based on the validation data, using the MSP2 test at 95 percent sensitivity for high-grade prostate cancer would avoid 37 percent of unnecessary biopsies. Use of the MSP2+ test would avoid 41 percent. Comparatively, the researchers found that using other well-known assays including PSA alone, the Prostate Cancer Prevention Trial risk calculator, the Prostate Health Index, the derived multiplex two-gene and three-gene models, and the original MPS test would result in the avoidance of anywhere from 11 percent to 27 percent of unnecessary biopsies.

Additionally, the authors noted, the MPS2 and MPS2+ tests both performed with 99 percent sensitivity and 99 percent negative predictive value for prostate cancer with a Gleason Group of 3 or greater.

"There was still an unmet need with the MyProstateScore test and other commercial tests currently available," Chinnaiyan said in a statement. "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."