Oncology| Volume 141, P119-124, July 2020

Download started.


Concordance and Performance of 4Kscore and SelectMDx for Informing Decision to Perform Prostate Biopsy and Detection of Prostate Cancer


      To compare both the concordance between the 4Kscore and SelectMDx for informing decision to perform prostate biopsy (PB) and the performance of these tests for detecting clinically significant prostate cancer (csPCa). Several biomarkers were developed to inform decisions whether to perform a PB based on the probability of detecting csPCa. There is a paucity of studies directly comparing them


      Between 11/2018 and 4/2019, all new referrals with the diagnosis of elevated PSA were advised to undergo 4Kscore and SelectMDx in order to guide the selection of candidates for PB. Men were advised to undergo PB if the reported biomarker risk for detecting csPCA was ≥7.5%, or if they presented a Prostate Image Reporting and Data System ≥1 MRI. Cohen's Kappa was used to assess the concordance between the binary 4Kscore and SelectMDx results using externally validated cutoffs of 7.5% and 12%. Receiver operating characteristics curve and area under the curve (AUC) assessed the performance of each biomarker for distinguishing csPCa.


      Of 128 consecutive patients referred, 114 (89.1%) underwent 4Kscore and SelectMDx. The kappa coefficient between the biomarkers using the 7.5% cutoff was 0.184 (poor concordance) and 0.22 using the 12% cutoff. The two biomarkers yielded discordant guidance whether to proceed with PB in 46% and 38% of cases, respectively. csPCa was found in 22 of the 50 patients who underwent PB (44%). The AUC for 4Kscore and SelectMDx was 0.830 (95% confidence interval [CI]: 0.710 - 0.949) and 0.672 (95%CI: 0.517 - 0.828; P = .036) for csPCa, respectively.


      The discordance observed between the 4Kscore and SelectMDx is disconcerting. The 4Kscore when combined with magnetic resonance imaging was superior to the SelectMDx for detecting csPCa. Prospective comparative studies must be performed to optimize implementation of biomarkers for selecting candidates for PB.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Urology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Welch HG
        • Kramer BS
        • Black WC
        Epidemiologic signatures in cancer.
        New Engl J Med. 2019; 381: 1378-1386
        • Moyer VA
        Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement.
        Ann Int Med. 2012; 157: 120-134
        • Kornberg Z
        • Cooperberg MR
        • Spratt DE
        • Feng FY
        Genomic biomarkers in prostate cancer.
        Transl Androl Urol. 2018; 7: 459-471
        • Hendriks RJ
        • van Oort IM
        • Schalken JA
        Blood-based and urinary prostate cancer biomarkers: a review and comparison of novel biomarkers for detection and treatment decisions.
        Prostate Cancer Prostatic Dis. 2017; 20: 12-19
        • Parekh DJ
        • Punnen S
        • Sjoberg DD
        • et al.
        A multi-institutional prospective trial in the USA confirms that the 4Kscore accurately identifies men with high-grade prostate cancer.
        Eur Urol. 2015; 68: 464-470
        • Zappala SM
        • Scardino PT
        • Okrongly D
        • Linder V
        • Dong Y
        Clinical performance of the 4Kscore Test to predict high-grade prostate cancer at biopsy: a meta-analysis of us and European clinical validation study results.
        Rev Urol. 2017; 19: 149-155
        • Leyten GH
        • Hessels D
        • Smit FP
        • et al.
        Identification of a candidate gene panel for the early diagnosis of prostate cancer.
        Clin Cancer Res. 2015; 21: 3061-3070
        • Haese A
        • Trooskens G
        • Steyaert S
        • et al.
        Multicenter optimization and validation of a 2-Gene mRNA urine test for detection of clinically significant prostate cancer prior to initial prostate biopsy.
        J Urol. 2019; 202: 256-263
        • Landis JR
        • Koch GG.
        The measurement of observer agreement for categorical data.
        Biometrics. 1977; 33: 159-174
        • Sanda MG
        • Cadeddu JA
        • Kirkby E
        • et al.
        Clinically localized prostate cancer: AUA/ASTRO/SUO guideline. Part II: recommended approaches and details of specific care options.
        J Urol. 2018; 199: 990-997
        • Guidelines EAU
        Prostate cancer guidelines.
        in: Presented at the EAU Annual Congress Barcelona 2019. 2019
        • Carroll PH
        • Mohler JL
        NCCN guidelines updates: prostate cancer and prostate cancer early detection.
        J Natl Comprehensive Cancer Netw. 2018; 16: 620-623
        • Dasgupta P
        • Davis J
        • Hughes S
        NICE guidelines on prostate cancer 2019.
        BJU Int. 2019; 124: 1
        • Wysock JS
        • Rosenkrantz AB
        • Huang WC
        • et al.
        A prospective, blinded comparison of magnetic resonance (MR) imaging-ultrasound fusion and visual estimation in the performance of MR-targeted prostate biopsy: the PROFUS trial.
        Eur Urol. 2014; 66: 343-351
        • Loeb S
        • Dani H
        Whom to biopsy: prediagnostic risk stratification with biomarkers, nomograms, and risk calculators.
        Urol Clin North Am. 2017; 44: 517-524
        • Van Neste L
        • Hendriks RJ
        • Dijkstra S
        • et al.
        Detection of high-grade prostate cancer using a urinary molecular biomarker-based risk score.
        Eur Urol. 2016; 70: 740-748
      1. NICE guidance - prostate cancer: diagnosis and management: (c) NICE (2019) Prostate cancer: diagnosis and management.
        BJU Int. 2019; 124: 9-26
        • Kasivisvanathan V
        • Rannikko AS
        • Borghi M
        • et al.
        MRI-targeted or standard biopsy for prostate-cancer diagnosis.
        N Engl J Med. 2018; 378: 1767-1777