CONTEXT: Many liquid biomarkers have entered clinical practice with the praise to improve the detection of clinically significant prostate cancer (csPCa), helping avoid unnecessary prostate biopsies. OBJECTIVE: We aimed to assess the diagnostic accuracy of multianalyte biomarkers for csPCa detection using multiple thresholds. EVIDENCE ACQUISITION: A comprehensive literature search was done through PubMed, Web of Science, and Scopus in March 2023 for prospective and retrospective studies reporting the diagnostic performance of liquid biomarkers for detecting csPCa. The outcomes of interest were the diagnostic performance of liquid biomarkers for csPCa detection and identification of optimal thresholds for each biomarker. EVIDENCE SYNTHESIS: Overall, 49 studies were eligible for this meta-analysis. Using each representative threshold based on the Youden Index, the pooled sensitivity and specificity for detecting csPCa were 0.85 and 0.37 for prostate cancer gene 3 (PCA3), 0.85 and 0.52 for prostate health index (PHI), 0.87 and 0.58 for four kallikrein (4K), 0.82 and 0.56 for SelectMDx, 0.85 and 0.54 for ExoDx, and 0.82 and 0.59 for mi prostate score (MPS), respectively. The diagnostic odds ratio was highest for 4K (8.84), followed by MPS (7.0) and PHI (6.28). According to the meta-analysis incorporating multiple thresholds, the corresponding sensitivity was 0.77 for 4K, 0.69 for PHI, and 0.63 for PCA3; specificity was 0.72 for PHI, 0.70 for 4K, and 0.69 for PCA3. CONCLUSIONS: Regarding the detection of csPCa, 4K had the highest diagnostic performance among the commercial liquid biomarkers. Based on the optimal thresholds calculated by the present meta-analysis, 4K had the highest sensitivity and PHI had the highest specificity for detecting csPCa. Nevertheless, clinical decision-making requires combination strategies between liquid and imaging biomarkers. PATIENT SUMMARY: Novel biomarkers for prostate cancer detection were useful for more accurate diagnosis of clinically significant prostate cancer to avoid unnecessary biopsies.

Cancer Prognostics and Health Outcomes Unit University of Montreal Health Centre Montreal Canada

Department of Biomedical Informatics College of Medicine Konyang University Daejeon Republic of Korea

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Cancer Prognostics and Health Outcomes Unit University of Montreal Health Centre Montreal Canada; Department of Urology Weill Cornell Medical College New York NY USA; Department of Urology University of Texas Southwestern Medical Center Dallas TX USA; Department of Urology 2nd Faculty of Medicine Charles University Prague Czech Republic; Hourani Center for Applied Scientific Research AI Ahliyya Amman University Amman Jordan; Research Center for Evidence Based Medicine Iranian EBM Center A Joanna Briggs Institute Center of Excellence Tabriz University of Medical Sciences Tabriz Iran

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Department of Urology King Fahad Specialist Hospital Dammam Saudi Arabia

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Department of Urology Medical University of Silesia Zabrze Poland

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Department of Urology Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Okayama Japan

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Department of Urology The Jikei University School of Medicine Tokyo Japan

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Department of Urology University Medical Center Hamburg Eppendorf Hamburg Germany

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Department of Urology UROSUD La Croix Du Sud Hospital Quint Fonsegrives France

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Institute for Urology and Reproductive Health Sechenov University Moscow Russia

Department of Urology Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Okayama Japan

S H Ho Urology Centre Department of Surgery The Chinese University of Hong Kong Hong Kong China

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