October 15, 2022
Refinement and External Validation of a Novel Multiplex Urine Test for High-Grade Prostate Cancer
The MyProstateScore (MPS) test employs the long non-coding RNA PCA3 and the TMPRSS2:ERG (T2:ERG) gene fusion to detect clinically-significant (Grade Group [GG]≥2) prostate cancer (PCa). To build upon MPS, we analyzed RNA-seq data from a PCa compendium, identifying 50 additional cancer- and high-grade cancer- specific markers. In total, 54 transcripts were measured by multiplex qPCR in 1504 urine biospecimens. The current study sought to develop and validate a novel urinary test for improved detection of GG≥2 PCa. In conclusion, incorporating novel transcripts associated with high-grade cancer, we externally validated a 17-marker urinary panel for detection of GG≥2 PCa. Compared to the clinically-available MPS test, the MPS2cv model improved diagnostic accuracy (AUC) by nearly 10% and increased specificity by 21% at clinically-actionable, highly- sensitive thresholds. These findings suggest that the MPS2 test meaningfully improves detection of GG≥2 PCa relative to current diagnostic tests and could contribute to a more optimal contemporary diagnostic pathway.