Multimodal urinary biomarker panel achieves superior prostate cancer detection accuracy and reduces unnecessary biopsies.

To address the persistent challenges associated with prostate-specific antigen (PSA) screening, a multicenter study was conducted to evaluate whether urinary microRNAs, in combination with the free-to-total PSA (f/tPSA) ratio, could improve prostate cancer (PCa) detection while minimizing unnecessary biopsies. The study included 307 men divided into three groups: 112 with confirmed PCa, 98 diagnosed with benign prostatic hyperplasia (BPH), and 97 healthy controls (HCs). Researchers measured serum PSA levels, inflammatory markers, and five urinary extracellular vesicle-derived miRNAs: miR-21-5p, miR-141-3p, miR-205-5p, miR-375, and miR-222-3p The analysis revealed distinct patterns of miRNA expression in the samples. The levels of miR-21-5p and miR-375 were significantly elevated in patients with PCa compared to those in the BPH and control groups (P < 0.001), whereas that of miR-205-5p was markedly reduced (P < 0.001). The f/tPSA ratio demonstrated superior discriminatory ability compared to standard PSA testing, with an area under the curve (AUC) of 0.829. However, integrating multiple biomarkers, including miR-21-5p, miR-375, free-to-total PSA ratio, PSA density, and neutrophil-to-lymphocyte ratio, further enhanced diagnostic accuracy. This combined model outperformed conventional approaches, yielding an AUC of 0.947 (95 % CI: 0.923-0.971) with 92.9 % sensitivity and 88.7 % specificity (P < 0.001). Notably, it exhibited exceptional performance within the PSA "gray zone" (4-10 ng/mL), a range where traditional screening methods often lead to diagnostic uncertainty and difficult biopsy decisions.