Novel non-invasive urine-based gene expression assay discriminates between low- and high-risk prostate cancer before biopsy

Prostate-specific antigen (PSA)-based screening programs are controversial, and influential guideline panels have recommended against PSA screening in all men. A main limitation of PSA-based blood tests is the lack of a valid threshold to distinguish between a malignant and a benign condition. In addition, PSA screening generally fails to differentiate between low- and high-grade prostate cancer and thus, is not able to prevent patients from unnecessary biopsies. Alternative, urine-based tests have recently been developed and provide promising predictive accuracy regarding the aggressiveness of the disease. Two markers—prostate cancer antigen 3 (PCA3) and an androgen-related fusion protein (TMPRSS2-ERG)—were combined into a urine test several years ago. This Mi-Prostate Score (MiPS) significantly outperformed both PCA3 + PSA and PSA alone for the prediction of high-grade prostate cancer before biopsy. To date, these tests need pre-collection digital rectal examination to improve the predictive ability. Against this backdrop, a recent study presented a novel urine-based assay, using an exosome-derived gene expression signature. In a validation cohort of 519 patients, the area under receiver operating characteristic curve (AUC) showed superior predictive ability in the discrimination of Gleason scores ≥7 and <7 before biopsy, when compared to standard of care alone (0.73 vs. 0.63; P<0.001). Despite not showing better predictive accuracy than already existing urine-based tests, this novel exosome-derived assay allows pre-biopsy assessment without the need for digital rectal examination. Thus, any health professional can perform the test, which (I) spares the patient another digital rectal examination and (II) may facilitate clinical workflow.