The potential of plasma-derived medium-sized extracellular vesicles as a biopsy alternative for active surveillance decisions in prostate Cancer.

Diagnosing prostate cancer (PCa) and risk-stratifying patients remains challenging, as PSA-based methods lack precision for active surveillance (AS) decision-making. Extracellular vesicles (EVs) are membranous nano-sized vesicles released by all types of cells and may contain potentially interesting material for diagnostic procedures for PCa. This study analyzed surface markers and miRNA profiles of medium-sized plasma EVs (mEVs) from 24 PCa patients using nanoflow cytometry and miRNA profiling. The ratio of PSMA+ EVs to PSMA+CD9+ EVs differed significantly between AS and non-AS patients. Additionally, miR-99a-5p, miR-125b-5p, miR-145-5p, and miR-365a-3p levels were higher in non-AS patients. These findings suggest that plasma-derived PSMA+ mEVs originate from the prostate and may serve as biomarkers for PCa progression. Nanoflow cytometry-based analysis of EV surface markers combined with miRNA profiling provides a novel, non-invasive alternative to PSA measurements. This approach could improve risk stratification and decision-making for AS patients, potentially leading to better outcomes.