New Prostate Cancer Urine Test Produces Greater Diagnostic Accuracy vs Existing Tests in High-Grade Prostate Cancer

Spencer Heaton, MD, MBA

The 18-gene urine test MyProstateScore 2.0 produced higher diagnostic accuracy for high-grade prostate cancer compared with existing biomarker tests, supporting the use of the new test in patients with elevated prostate-specific antigen (PSA) levels to reduce the potential harms of prostate cancer screening.^1,2

In the test validation cohort (n = 743), the area under the receiver operating characteristic curve (AUC) values were 0.81 (95% CI, 76.9-84.6) for MyProstateScore 2.0 without prostate volume and 0.82 (95% CI, 78.1-85.5) for MyProstateScore 2.0 with prostate volume. Comparatively, the AUC values were as follows using: PSA alone, 0.60 (95% CI, 54.7-64.6); the Prostate Cancer Prevention Trial risk calculator, 0.66 (95% CI, 61.1-70.7); the Prostate Health Index, 0.77 (95% CI, 73.0-81.3); a derived multiplex 2-gene model, 0.76 (95% CI, 71.9-80.3); a derived multiplex 3-gene model, 0.72 (95% CI, 67.0-76.1); and the original MyProstateScore model, 0.74 (95% CI, 69.4-78.0).

Additionally, at 95% sensitivity, the MyProstateScore 2.0 model would have reduced unnecessary biopsies performed in the initial biopsy population (n = 496) compared with the other tests; the proportion of unnecessary biopsies avoided were 15% for PSA alone, 27% for the Prostate Cancer Prevention Trial risk calculator, 30% for the Prostate Health Index, 30% for the derived multiplex 2-gene model, 17% for the derived multiplex 3-gene model, and 27% for the original MyProstateScore model compared with 35% for MyProstateScore 2.0.²

“The research findings confirm the role of MyProstateScore 2.0 to guide a more informed decision about whether to proceed with a prostate biopsy—a decision that is notoriously difficult to get right,” Spencer Heaton, MD, MBA, the chief medical officer of Lynx Dx, the developer of MyProstateScore 2.0, stated in a press release. “Lynx Dx’s goal is to provide best-in-class diagnostic tests that enable urologists and patients to make confident decisions, while greatly improving the rate of life-saving early detection.”¹

MyProstateScore 2.0 is built on the original MyProstateScore test which incorporated prostate cancer antigen 3 and TMPRSS2:ERG gene fusion expression with serum PSA level to estimate the risk of high-grade cancers. The original MyProstateScore is endorsed by NCCN guidelines for prebiopsy risk stratification. The developers of MyProstateScore 2.0 performed a differential expression analysis of 58,724 genetic targets in multi-institutional RNA sequencing data, identifying 72 genes that met the nomination criteria for cancer or high-grade cancer; 10 previously described prostate cancer or reference genes were added to the 44 candidate markers after removing collinear genes and those without PCR primers to create a 54-gene candidate panel.²

Using the candidate panel, investigators created the optimized 18-gene panel and tested it with and without prostate volume data.The final MyProstateScore 2.0 model included 4 high-grade cancer–specific genes (APOC1, B3GNT6, NKAIN1, and SCHLAP1) 9 cancer-specific genes (PCGEM1, SPON2, TRGV9, PCA3, OR51E2, CAMKK2, TFF3, PCAT14, and TMSB15A), 4 curated markers (HOXC6, ERG, TMPRSS2:ERG, and KLK4), and the reference gene KLK3.

To evaluate the model, investigators enrolled an external validation cohort of patients from the prospective NCI EDRN PCA3 Evaluation Trial which enrolled patients across 11 academic centers. They performed specimen laboratory analysis as well as a blinded validation and comparative analysis. The objective of the study was to develop a multiplex urinary panel for high-grade prostate cancer and validate its external performance relative to current guideline-endorsed biomarkers.

At baseline in the developmental cohort (n = 815) quantitative PCR yielded results in 93.4% of patients; the median age was 63 years (IQR, 58-68) and the median PSA level was 5.6 ng/mL (IQR, 4.6-7.2). In the validation cohort (n = 813), quantitative PCR was successful in 91.4% of patients; the median age was 62 years (IQR, 57-68) and the median PSA level was 5.6 ng/mL (IQR, 4.1-8.0). Further, 20.3% of patients had high-grade prostate cancer on study biopsy and 33.2% previously had a negative biopsy.

Additional findings from the study showed that in the repeat biopsy population (n = 247), consisting of patients with a median PSA level of 7.2 ng/mL (IQR, 5.5-9.8)—7.3% of which had high-grade cancer—the proportions of unnecessary biopsies that would have been avoided at 95% sensitivity were 15% for PSA alone, 8.7% for Prostate Health Index, 14% for the derived multiplex 2-gene model, 16% for the derived multiplex 3-gene model, 15% for the original MyProstateScore, 46% for MyProstateScore 2.0 without prostate volume, and 51% for MyProstateScore 2.0 with prostate volume. Study authors noted that MyProstateScore 2.0 testing would have avoided approximately 50% of unnecessary biopsies with a detection rate of 94.4% for high-grade cancers.

“In this study, within an external validation population referred for prostate biopsy, an 18-gene urinary test had higher diagnostic accuracy for high-grade prostate cancer beyond currently available testing options. Clinically, use of this test would have safely avoided unnecessary additional testing with imaging or biopsy in 35% to 51% of patients while maintaining high sensitivity for high-grade cancers that stand to benefit from early detection. These findings suggest that use of the test in patients with elevated PSA levels can reduce the potential harms of prostate cancer screening while preserving its long-term benefits,” study authors wrote in conclusion.

References

1. Development and validation of an 18-gene urine test for high-grade prostate cancer. News release. Lynx Dx. April 18, 2024. Accessed April 22, 2024. https://www.lynxdx.com/2024/04/news/mps2-clinically-validated-jama-oncology/
2. Tosoian JJ, Zhang Y, Xiao L, et al. Development and validation of an 18-gene urine test for high-grade prostate cancer. JAMA Oncol. Published online April 18, 2024. doi:10.1001/jamaoncol.2024.0455