Aims: To evaluate, compare, and accurately synthesize the diagnostic performance of circulating microRNAs miR-21, miR-141, and miR-375 as non-invasive biomarkers for prostate cancer, both individually and in combination, to determine their added value compared to conventional methods (PSA and biopsy) and to provide robust conclusions from heterogeneous literature data. Background: Prostate cancer represents a major public health challenge, with diagnostic limitations related to prostate-specific antigen (PSA) testing. In response to these challenges, circulating microRNAs, particularly miR-21, miR-141, and miR-375, emerge as promising non-invasive biomarkers that could improve early prostate cancer detection. Methods: A meta-analysis was conducted, and publications from January 2008 to April 2025 were selected from PubMed, Embase, ScienceDirect, and Scopus databases. This meta-analysis included studies on the diagnostic performance of circulating microRNAs -21, -141, and -375 in patients with prostate cancer and in control subjects (healthy or with benign prostatic hyperplasia), whose diagnosis had been confirmed or ruled out by prostate biopsy. Pooled measures of sensitivity, specificity, area under the ROC curve (AUC), likelihood ratios, and diagnostic odds ratios (DOR) were calculated using a bivariate random-effects model. A subgroup analysis was performed to explore sources of heterogeneity. Results: A total of 25 eligible studies, with 27 datasets, comprising 2,697 participants (1,525 prostate cancer patients and 1,172 controls) were analyzed. miR-21 demonstrated the highest diagnostic performance, with pooled sensitivity and specificity of 0.87 and 0.86, respectively, and an AUC of 0.92. miR-141 showed slightly lower performance, with an AUC of 0.87. Although less robust, miR-375 still exhibited moderate diagnostic value, yielding an AUC of 0.88. The combination of all three miRNAs achieved an overall diagnostic accuracy of 0.82 for sensitivity and 0.86 for specificity, with an AUC of 0.91. Subgroup analyses revealed that whole blood performed best (AUC = 0.91), albeit with substantial heterogeneity (I² = 91.8%). Conclusion: These findings highlight the strong potential of circulating miRNAs as promising diagnostic tools for prostate cancer, outperforming conventional PSA testing. However, standardized prospective studies remain necessary before clinical implementation can be recommended.

Urinary; Blood; miR-2; miR-141; miR-375; Biomarkers