MPS2-AS testing model (urine testing) and prostate cancer

The MPS2 (MyProstateScore 2.0) is an 18-gene urinary test developed to identify high-grade (clinically significant) prostate cancer.

• the 18-gene MyProstateScore 2.0 (MPS2) test, previously validated using post–digital rectal examination (DRE) urine, has been shown to preserve detection of clinically significant prostate cancers (grade group [GG] ≥2) while reducing the rate of biopsies (1)
  • on validation, MPS2 testing with 95% sensitivity for high-grade cancer had 95% to 99% NPV and 35% to 51% specificity across subgroups
  • uniform use of MPS2 could avoid unnecessary biopsies while preserving immediate detection of 95% of cancers of GG 2 or greater diagnosed using the biopsy all approach
  • MPS2 had 99% sensitivity and 99% NPV for cancers of GG 3 or greater, meaning the rare false-negative MPS2 results were almost uniformly more favourable cancers of GG 2 least likely to metastasize

A study validated the MPS2 test using first-catch, non-DRE urine (2):

• study results showed that
  • in men considering prostate biopsy, non-DRE MPS2 testing significantly reduced the need for biopsy compared with the Prostate Cancer Prevention Trial risk calculator (PCPTrc) while maintaining reliable detection of GG ≥ 2 cancers.
  • under a testing approach maintaining 92% sensitivity for GG ≥ 2 cancer in the overall population, MPS2 testing would have avoided 36% to 42% of unnecessary biopsies, as compared with 13% using the PCPTrc
  • in patients considering repeat biopsy, MPS2 testing would have avoided 44% to 53% of unnecessary biopsies, as compared with only 2.6% using the PCPTrc
• study authors concluded that:
  • using urine obtained without DRE, the MPS2 test provides a highly accurate, personalized risk score to better identify patients who can confidently forgo additional testing with MRI or biopsy

A simplified version of MPS2 has been investigated (3):

• final sMPS2 model consisted of 7 genes and achieved a 0.784 AUROC (95% confidence interval, 0.742–0.825) for predicting high-grade PCa on a blinded external validation cohort
  • is 2.3% lower than the 18-gene MPS2, which is similar in magnitude to the 1–2% in uncertainty induced by different data preprocessing choices

Reference:

1. Tosoian J et al; EDRN-PCA3 Study Group. Development and Validation of an 18-Gene Urine Test for High-Grade Prostate Cancer. JAMA Oncol. 2024 Jun 1;10(6):726-736.
2. Tosoian JJ et al. Clinical Validation of MyProstateScore 2.0 Testing Using First-Catch, Non-Digital Rectal Examination Urine. J Urol. 2025 May;213(5):581-589.
3. Tang TM et al. A simplified MyProstateScore2.0 for high-grade prostate cancer. Cancer Biomark. 2025 Jan;42(1):18758592241308755.