Diagnostic Accuracy of Liquid Biomarkers for Clinically Significant Prostate Cancer Detection: A Systematic Review and Diagnostic Meta-analysis of Multiple Thresholds

Tatsushi Kawada; Sung Ryul Shim; Fahad Quhal; Pawel Rajwa; Benjamin Pradere; Takafumi Yanagisawa; Kensuke Bekku; Ekaterina Laukhtina; Markus von Deimling; Jeremy Yuen-Chun Teoh; Pierre I Karakiewicz; Motoo Araki; Shahrokh F Shariat

doi:10.1016/j.euo.2023.10.029

Diagnostic Accuracy of Liquid Biomarkers for Clinically Significant Prostate Cancer Detection: A Systematic Review and Diagnostic Meta-analysis of Multiple Thresholds

Eur Urol Oncol. 2023 Nov 17:S2588-9311(23)00248-1. doi: 10.1016/j.euo.2023.10.029. Online ahead of print.

Authors

Affiliations

¹ 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.
² Department of Biomedical Informatics, College of Medicine, Konyang University, Daejeon, Republic of Korea.
³ Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, King Fahad Specialist Hospital, Dammam, Saudi Arabia.
⁴ Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Medical University of Silesia, Zabrze, Poland.
⁵ Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology UROSUD, La Croix Du Sud Hospital, Quint Fonsegrives, France.
⁶ Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, The Jikei University School of Medicine, Tokyo, Japan.
⁷ Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia.
⁸ Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁹ S.H. Ho Urology Centre, Department of Surgery, The Chinese University of Hong Kong, Hong Kong, China.
¹⁰ Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal, Canada.
¹¹ Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
¹² 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, Second 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. Electronic address: shahrokh.shariat@meduniwien.ac.at.

PMID: 37981495
DOI: 10.1016/j.euo.2023.10.029

Abstract

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.

Keywords: Biomarker; Clinically significant prostate cancer; Diagnosis; Prostate biopsy; Prostate cancer.

Publication types

Review