Transforming Prostate Cancer Screening: The MPS2 Breakthrough

Prostate cancer stands out as a leading cause of male mortality nationwide. The diagnostic procedure for this ailment typically involves a blood analysis aimed at quantifying levels of prostate-specific antigen (PSA), a substance originating from the prostate gland. Elevated PSA concentrations may indicate the presence of prostate cancer or certain non-cancerous conditions, such as prostatic inflammation.

Increased PSA levels can trigger additional assessments, including a biopsy. This invasive procedure involves extracting around twelve small tissue samples from various areas of the prostate gland to examine for cancerous cells. Although biopsies are generally safe, they can cause discomfort and lead to adverse effects like fever, urinary tract infections, or other complications. Often, biopsies help identify slow-growing prostate cancers that require close monitoring rather than immediate treatment.

Researchers have been striving to avoid unnecessary biopsies by exploring noninvasive methods to distinguish between aggressive prostate cancers requiring intervention and slow-growing cancers that may not necessitate immediate treatment.

About a decade ago, a team supported by the National Institutes of Health and led by Dr. Arul M. Chinnaiyan from the University of Michigan developed a urine-based diagnostic tool called MyProstateScore (MPS), which is still in use. Based on the presence of two specific genes frequently elevated in the urine of men with prostate cancer, MPS aids in the early detection of prostate malignancies. However, it lacks the ability to differentiate between low-grade and high-grade cancers of greater severity.

In their recent study, a team led by Chinnaiyan and Dr. Jeffrey Tosoian of Vanderbilt University aimed to identify a group of urinary genetic elements capable of distinguishing aggressive forms of prostate cancers. Their findings were published on April 18, 2024, in JAMA Oncology.

The researchers initially analyzed RNA sequencing data from nearly 59,000 genes to identify a list of 54 potential markers. Each of these markers was associated with either prostate cancer as a whole or specifically linked to high-grade malignancies, all detectable within urine samples. Further analyses and computational simulations conducted on 761 subjects led to the identification of a subset comprising 17 genes deemed most proficient at predicting the presence of high-grade cancers. Additionally, a reference gene associated with general prostatic tissue was incorporated into the panel. This new 18-gene assessment was named MyProstateScore 2.0 (MPS2).

MPS2 was validated by examining urine samples from an additional cohort of 743 individuals. Each participant underwent a biopsy due to elevated PSA levels, revealing that 20% of them harbored high-grade prostate cancer.

Validation analysis showed that MPS2 could rule out the presence of high-grade cancer with 97% accuracy. The researchers compared MPS2 with results from various biomarker tests, including the original MPS assay. Comparative analysis revealed MPS2's superior ability to discern high-grade cancers. The investigators estimated that it could potentially reduce the need for up to 51% of unnecessary biopsies, providing significant clinical benefits.

"In approximately 800 individuals exhibiting elevated PSA levels, the new test demonstrated its capability to rule out clinically significant prostate cancer with remarkable precision," remarked Tosoian. "This enables patients to avoid more burdensome and invasive tests, such as MRI and prostatic biopsy, with great confidence that no crucial aspect is overlooked."

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