title: The prostate cancer detection rates of CEUS-targeted versus MRI-targeted versus systematic TRUS-guided biopsies in biopsy-naïve men: a prospective, comparative clinical trial using the same patients.
abstract: BACKGROUND
  The current standard for Prostate Cancer (PCa) detection in biopsy-naïve men consists of 10-12 systematic biopsies under ultrasound guidance. This approach leads to underdiagnosis and undergrading of significant PCa while insignificant PCa may be overdiagnosed. The recent developments in MRI and Contrast Enhanced Ultrasound (CEUS) imaging have sparked an increasing interest in PCa imaging with the ultimate goal of replacing these "blind" systematic biopsies with reliable imaging-based targeted biopsies.
  
  
  METHODS
  In this trial, we evaluate and compare the PCa detection rates of multiparametric (mp)MRI-targeted biopsies, CEUS-targeted biopsies and systematic biopsies under ultrasound guidance in the same patients. After informed consent, 299 biopsy-naïve men will undergo mpMRI scanning and CEUS imaging 1 week prior to the prostate biopsy procedure. During the biopsy procedure, a systematic transrectal 12-core biopsy will be performed by one operator blinded for the imaging results and targeted biopsy procedure. Subsequently a maximum of 4 CEUS-targeted biopsies and/or 4 mpMRI-targeted biopsies of predefined locations determined by an expert CEUS reader using quantification techniques and an expert radiologist, respectively, will be taken by a second operator using an MRI-US fusion device. The primary outcome is the detection rate of PCa (all grades) and clinically significant PCa (defined as Gleason score ≥7) compared between the three biopsy protocols.
  
  
  CONCLUSIONS
  This trial compares the detection rate of (clinically significant) PCa, between both traditional systematic biopsies and targeted biopsies based on predefined regions of interest identified by two promising imaging technologies. It follows published recommendations on study design for the evaluation of imaging guided prostate biopsy techniques, minimizing bias and allowing data pooling. It is the first trial to combine mpMRI imaging and advanced CEUS imaging with quantification.
  
  
  BACKGROUND
  The Dutch Central Committee on Research Involving Human Subjects registration number NL52851.018.15, registered on 3 Nov 2015. Clinicaltrials.gov database registration number NCT02831920 , retrospectively registered on 5 July 2016.
authors.affiliation: Department of Urology, AMC University Hospital, Amsterdam, The Netherlands. a.w.postema@amc.nl.
authors.forename: A W
authors.initials: AW
authors.lastname: Postema
authors.affiliation: Department of Urology, AMC University Hospital, Amsterdam, The Netherlands.
authors.forename: M J V
authors.initials: MJ
authors.lastname: Scheltema
authors.affiliation: Department of Urology, AMC University Hospital, Amsterdam, The Netherlands.
authors.forename: C K
authors.initials: CK
authors.lastname: Mannaerts
authors.affiliation: Department of Electrical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
authors.forename: R J G
authors.initials: RJ
authors.lastname: Van Sloun
authors.affiliation: Department of Urology, AMC University Hospital, Amsterdam, The Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Idzenga
authors.affiliation: Department of Electrical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Mischi
authors.affiliation: Department of Radiology, AMC University Hospital, Amsterdam, The Netherlands.
authors.forename: M R E
authors.initials: MR
authors.lastname: Engelbrecht
authors.affiliation: Department of Urology, AMC University Hospital, Amsterdam, The Netherlands.
authors.forename: J J M C H
authors.initials: JJ
authors.lastname: De la Rosette
authors.affiliation: Department of Urology, AMC University Hospital, Amsterdam, The Netherlands.|Department of Electrical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Wijkstra
mesh_terms: D000328:Adult; D003287:Contrast Media; D006801:Humans; D061705:Image-Guided Biopsy / Q000379:methods*; D016015:Logistic Models; D008279:Magnetic Resonance Imaging; D008297:Male; D011446:Prospective Studies; D011467:Prostate / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000473:pathology*; D014463:Ultrasonography / Q000379:methods
chemical_list: D003287:Contrast Media
keywords: CEUS; Contrast enhanced ultrasound; Prostate cancer; Prostate cancer imaging; Targeted prostate biopsies; mpMRI