A new 18-gene urine test for high-grade prostate cancer (GG 2 or greater) was developed and validated in a study published in JAMA Oncology. The test, called MyProstateScore 2.0 (MPS2), outperformed existing biomarker tests in detecting high-grade prostate cancer. The study involved 761 men in the development cohort and 743 men in the validation cohort. The test demonstrated higher diagnostic accuracy compared to PSA alone, the Prostate Cancer Prevention Trial risk calculator, and the Prostate Health Index (PHI). At 95% sensitivity for high-grade cancer, the MPS2 model reduced unnecessary biopsies by 35% to 42% in the initial biopsy population and by 46% to 51% in the repeat biopsy population. The test also showed high negative predictive values (95% to 99%) for cancers of GG 2 or greater and 99% for cancers of GG 3 or greater. The study supports the use of this new biomarker test in patients with elevated PSA levels to reduce the potential harms of prostate cancer screening while preserving its long-term benefits. The test uses 17 markers of cancer and includes novel markers uniquely overexpressed by high-grade cancers. The study highlights the need for more accurate and specific biomarkers to improve prostate cancer screening outcomes.A new 18-gene urine test for high-grade prostate cancer (GG 2 or greater) was developed and validated in a study published in JAMA Oncology. The test, called MyProstateScore 2.0 (MPS2), outperformed existing biomarker tests in detecting high-grade prostate cancer. The study involved 761 men in the development cohort and 743 men in the validation cohort. The test demonstrated higher diagnostic accuracy compared to PSA alone, the Prostate Cancer Prevention Trial risk calculator, and the Prostate Health Index (PHI). At 95% sensitivity for high-grade cancer, the MPS2 model reduced unnecessary biopsies by 35% to 42% in the initial biopsy population and by 46% to 51% in the repeat biopsy population. The test also showed high negative predictive values (95% to 99%) for cancers of GG 2 or greater and 99% for cancers of GG 3 or greater. The study supports the use of this new biomarker test in patients with elevated PSA levels to reduce the potential harms of prostate cancer screening while preserving its long-term benefits. The test uses 17 markers of cancer and includes novel markers uniquely overexpressed by high-grade cancers. The study highlights the need for more accurate and specific biomarkers to improve prostate cancer screening outcomes.