title: Identification of threshold prostate specific antigen levels to optimize the detection of clinically significant prostate cancer by magnetic resonance imaging/ultrasound fusion guided biopsy.
abstract: OBJECTIVE
  Prostate specific antigen sensitivity increases with lower threshold values but with a corresponding decrease in specificity. Magnetic resonance imaging/ultrasound targeted biopsy detects prostate cancer more efficiently and of higher grade than standard 12-core transrectal ultrasound biopsy but the optimal population for its use is not well defined. We evaluated the performance of magnetic resonance imaging/ultrasound targeted biopsy vs 12-core biopsy across a prostate specific antigen continuum.
  
  
  METHODS
  We reviewed the records of all patients enrolled in a prospective trial who underwent 12-core transrectal ultrasound and magnetic resonance imaging/ultrasound targeted biopsies from August 2007 through February 2014. Patients were stratified by each of 4 prostate specific antigen cutoffs. The greatest Gleason score using either biopsy method was compared in and across groups as well as across the population prostate specific antigen range. Clinically significant prostate cancer was defined as Gleason 7 (4 + 3) or greater. Univariate and multivariate analyses were performed.
  
  
  RESULTS
  A total of 1,003 targeted and 12-core transrectal ultrasound biopsies were performed, of which 564 diagnosed prostate cancer for a 56.2% detection rate. Targeted biopsy led to significantly more upgrading to clinically significant disease compared to 12-core biopsy. This trend increased more with increasing prostate specific antigen, specifically in patients with prostate specific antigen 4 to 10 and greater than 10 ng/ml. Prostate specific antigen 5.2 ng/ml or greater captured 90% of upgrading by targeted biopsy, corresponding to 64% of patients who underwent multiparametric magnetic resonance imaging and subsequent fusion biopsy. Conversely a greater proportion of clinically insignificant disease was detected by 12-core vs targeted biopsy overall. These differences persisted when controlling for potential confounders on multivariate analysis.
  
  
  CONCLUSIONS
  Prostate cancer upgrading with targeted biopsy increases with an increasing prostate specific antigen cutoff. Above a prostate specific antigen threshold of 5.2 ng/ml most upgrading to clinically significant disease was achieved by targeted biopsy. In our population this corresponded to potentially sparing biopsy in 36% of patients who underwent multiparametric magnetic resonance imaging. Below this value 12-core biopsy detected more clinically insignificant cancer. Thus, the diagnostic usefulness of targeted biopsy is optimized in patients with prostate specific antigen 5.2 ng/ml or greater.
authors.affiliation: Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Nabeel A
authors.initials: NA
authors.lastname: Shakir
authors.affiliation: Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Arvin K
authors.initials: AK
authors.lastname: George
authors.affiliation: Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: M Minhaj
authors.initials: MM
authors.lastname: Siddiqui
authors.affiliation: Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Jason T
authors.initials: JT
authors.lastname: Rothwax
authors.affiliation: Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Soroush
authors.initials: S
authors.lastname: Rais-Bahrami
authors.affiliation: Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Lambros
authors.initials: L
authors.lastname: Stamatakis
authors.affiliation: Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Su
authors.affiliation: Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Chinonyerem
authors.initials: C
authors.lastname: Okoro
authors.affiliation: Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Dima
authors.initials: D
authors.lastname: Raskolnikov
authors.affiliation: Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Annerleim
authors.initials: A
authors.lastname: Walton-Diaz
authors.affiliation: Biometric Research Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Richard
authors.initials: R
authors.lastname: Simon
authors.affiliation: Molecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Baris
authors.initials: B
authors.lastname: Turkbey
authors.affiliation: Molecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Choyke
authors.affiliation: Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Merino
authors.affiliation: Center for Interventional Oncology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; Clinical Center, National Institutes of Health, Bethesda, Maryland.
authors.forename: Bradford J
authors.initials: BJ
authors.lastname: Wood
authors.affiliation: Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; Center for Interventional Oncology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; Clinical Center, National Institutes of Health, Bethesda, Maryland. Electronic address: pintop@mail.nih.gov.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Pinto
mesh_terms: D001707:Biopsy, Needle / Q000379:methods; D006801:Humans; D061705:Image-Guided Biopsy; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011467:Prostate / Q000000981:diagnostic imaging / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000000981:diagnostic imaging / Q000473:pathology*; D018084:Ultrasonography, Interventional
chemical_list: D017430:Prostate-Specific Antigen
keywords: biopsy; diagnostic imaging; prostate; prostate-specific antigen; prostatic neoplasms