title: Prospective randomized trial comparing magnetic resonance imaging (MRI)-guided in-bore biopsy to MRI-ultrasound fusion and transrectal ultrasound-guided prostate biopsy in patients with prior negative biopsies.
abstract: BACKGROUND
  A significant proportion of prostate cancers (PCas) are missed by conventional transrectal ultrasound-guided biopsy (TRUS-GB). It remains unclear whether the combined approach using targeted magnetic resonance imaging (MRI)-ultrasound fusion-guided biopsy (FUS-GB) and systematic TRUS-GB is superior to targeted MRI-guided in-bore biopsy (IB-GB) for PCa detection.
  
  
  OBJECTIVE
  To compare PCa detection between IB-GB alone and FUS-GB + TRUS-GB in patients with at least one negative TRUS-GB and prostate-specific antigen ≥4 ng/ml.
  
  
  METHODS
  Patients were prospectively randomized after multiparametric prostate MRI to IB-GB (arm A) or FUS-GB + TRUS-GB (arm B) from November 2011 to July 2014.
  
  
  METHODS
  The study was powered at 80% to demonstrate an overall PCa detection rate of ≥60% in arm B compared to 40% in arm A. Secondary endpoints were the distribution of highest Gleason scores, the rate of detection of significant PCa (Gleason ≥7), the number of biopsy cores to detect one (significant) PCa, the positivity rate for biopsy cores, and tumor involvement per biopsy core.
  
  
  CONCLUSIONS
  The study was halted after interim analysis because the primary endpoint was not met. The trial enrolled 267 patients, of whom 210 were analyzed (106 randomized to arm A and 104 to arm B). PCa detection was 37% in arm A and 39% in arm B (95% confidence interval for difference, -16% to 11%; p=0.7). Detection rates for significant PCa (29% vs 32%; p=0.7) and the highest percentage tumor involvement per biopsy core (48% vs 42%; p=0.4) were similar between the arms. The mean number of cores was 5.6 versus 17 (p<0.001). A limitation is the limited number of patients because of early cessation of accrual.
  
  
  CONCLUSIONS
  This trial failed to identify an important improvement in detection rate for the combined biopsy approach over MRI-targeted biopsy alone. A prospective comparison between MRI-targeted biopsy alone and systematic TRUS-GB is justified.
  
  
  RESULTS
  Our randomized study showed similar prostate cancer detection rates between targeted prostate biopsy guided by magnetic resonance imaging and the combination of targeted biopsy and systematic transrectal ultrasound-guided prostate biopsy. An important improvement in detection rates using the combined biopsy approach can be excluded.
authors.affiliation: Department of Urology, Heinrich-Heine University, Düsseldorf, Germany. Electronic address: christian.arsov@med.uni-duesseldorf.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Arsov
authors.affiliation: Department of Urology, Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Rabenalt
authors.affiliation: Department of Diagnostic and Interventional Radiology, University Dusseldorf, Medical Faculty, D-40225 Düsseldorf, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Blondin
authors.affiliation: Department of Diagnostic and Interventional Radiology, University Dusseldorf, Medical Faculty, D-40225 Düsseldorf, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Quentin
authors.affiliation: Department of Urology, Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hiester
authors.affiliation: Division of Statistics, Department of Cardiovascular Surgery, Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: Erhard
authors.initials: E
authors.lastname: Godehardt
authors.affiliation: Department of Pathology, Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: Helmut E
authors.initials: HE
authors.lastname: Gabbert
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center Heidelberg, Heidelberg, Germany.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Becker
authors.affiliation: Department of Diagnostic and Interventional Radiology, University Dusseldorf, Medical Faculty, D-40225 Düsseldorf, Germany.
authors.forename: Gerald
authors.initials: G
authors.lastname: Antoch
authors.affiliation: Department of Urology, Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Albers
authors.affiliation: Department of Diagnostic and Interventional Radiology, University Dusseldorf, Medical Faculty, D-40225 Düsseldorf, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Schimmöller
mesh_terms: D000368:Aged; D003951:Diagnostic Errors; D061765:Endoscopic Ultrasound-Guided Fine Needle Aspiration; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D061705:Image-Guided Biopsy / Q000379:methods*; D007610:Kallikreins / Q000097:blood; D053783:Magnetic Resonance Imaging, Interventional; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011237:Predictive Value of Tests; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology*
chemical_list: C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: Magnetic resonance imaging-ultrasound fusion–guided prostate biopsy; Magnetic resonance imaging–guided in-bore prostate biopsy; Multiparametric magnetic resonance imaging; Prostate cancer; Randomized trial