title: Prostate Health Index improves multivariable risk prediction of aggressive prostate cancer.
abstract: To examine the use of the Prostate Health Index (PHI) as a continuous variable in multivariable risk assessment for aggressive prostate cancer in a large multicentre US study.
  
  
  
  The study population included 728 men, with prostate-specific antigen (PSA) levels of 2-10 ng/mL and a negative digital rectal examination, enrolled in a prospective, multi-site early detection trial. The primary endpoint was aggressive prostate cancer, defined as biopsy Gleason score ≥7. First, we evaluated whether the addition of PHI improves the performance of currently available risk calculators (the Prostate Cancer Prevention Trial [PCPT] and European Randomised Study of Screening for Prostate Cancer [ERSPC] risk calculators). We also designed and internally validated a new PHI-based multivariable predictive model, and created a nomogram.
  
  
  
  Of 728 men undergoing biopsy, 118 (16.2%) had aggressive prostate cancer. The PHI predicted the risk of aggressive prostate cancer across the spectrum of values. Adding PHI significantly improved the predictive accuracy of the PCPT and ERSPC risk calculators for aggressive disease. A new model was created using age, previous biopsy, prostate volume, PSA and PHI, with an area under the curve of 0.746. The bootstrap-corrected model showed good calibration with observed risk for aggressive prostate cancer and had net benefit on decision-curve analysis.
  
  
  
  Using PHI as part of multivariable risk assessment leads to a significant improvement in the detection of aggressive prostate cancer, potentially reducing harms from unnecessary prostate biopsy and overdiagnosis.
authors.affiliation: Department of Urology and Population Health, NYU Langone Medical Center, New York, NY, USA.
authors.forename: Stacy
authors.initials: S
authors.lastname: Loeb
authors.affiliation: Beckman Coulter Incorporated, Carlsbad, CA, USA.
authors.forename: Sanghyuk S
authors.initials: SS
authors.lastname: Shin
authors.affiliation: Beckman Coulter Incorporated, Carlsbad, CA, USA.
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Broyles
authors.affiliation: Department of Urology, University of Michigan School of Medicine, Ann Arbor, MI, USA.
authors.forename: John T
authors.initials: JT
authors.lastname: Wei
authors.affiliation: Department of Urology, Emory University and Emory Healthcare, Atlanta, GA, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Sanda
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: George
authors.initials: G
authors.lastname: Klee
authors.affiliation: Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Alan W
authors.initials: AW
authors.lastname: Partin
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Lori
authors.initials: L
authors.lastname: Sokoll
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Chan
authors.affiliation: Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Chris H
authors.initials: CH
authors.lastname: Bangma
authors.affiliation: Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Ron H N
authors.initials: RHN
authors.lastname: van Schaik
authors.affiliation: Vanguard Urologic Institute and Texas Prostate Center, Houston, TX, USA.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Slawin
authors.affiliation: Department of Urology, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Leonard S
authors.initials: LS
authors.lastname: Marks
authors.affiliation: Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Catalona
mesh_terms: D001707:Biopsy, Needle; D003661:Decision Support Techniques; D051517:Digital Rectal Examination; D055088:Early Detection of Cancer / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011446:Prospective Studies; D011467:Prostate / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology*; D018570:Risk Assessment
chemical_list: D017430:Prostate-Specific Antigen
keywords: Prostate Health Index; nomogram; prostate biopsy; prostate cancer; risk assessment