title: Combined Clinical Parameters and Multiparametric Magnetic Resonance Imaging for Advanced Risk Modeling of Prostate Cancer-Patient-tailored Risk Stratification Can Reduce Unnecessary Biopsies.
abstract: Multiparametric magnetic resonance imaging (mpMRI) is gaining widespread acceptance in prostate cancer (PC) diagnosis and improves significant PC (sPC; Gleason score≥3+4) detection. Decision making based on European Randomised Study of Screening for PC (ERSPC) risk-calculator (RC) parameters may overcome prostate-specific antigen (PSA) limitations.
  
  
  
  We added pre-biopsy mpMRI to ERSPC-RC parameters and developed risk models (RMs) to predict individual sPC risk for biopsy-naïve men and men after previous biopsy.
  
  
  
  We retrospectively analyzed clinical parameters of 1159 men who underwent mpMRI prior to MRI/transrectal ultrasound fusion biopsy between 2012 and 2015.
  
  
  
  Multivariate regression analyses were used to determine significant sPC predictors for RM development. The prediction performance was compared with ERSPC-RCs, RCs refitted on our cohort, Prostate Imaging Reporting and Data System (PI-RADS) v1.0, and ERSPC-RC plus PI-RADSv1.0 using receiver-operating characteristics (ROCs). Discrimination and calibration of the RM, as well as net decision and reduction curve analyses were evaluated based on resampling methods.
  
  
  
  PSA, prostate volume, digital-rectal examination, and PI-RADS were significant sPC predictors and included in the RMs together with age. The ROC area under the curve of the RM for biopsy-naïve men was comparable with ERSPC-RC3 plus PI-RADSv1.0 (0.83 vs 0.84) but larger compared with ERSPC-RC3 (0.81), refitted RC3 (0.80), and PI-RADS (0.76). For postbiopsy men, the novel RM's discrimination (0.81) was higher, compared with PI-RADS (0.78), ERSPC-RC4 (0.66), refitted RC4 (0.76), and ERSPC-RC4 plus PI-RADSv1.0 (0.78). Both RM benefits exceeded those of ERSPC-RCs and PI-RADS in the decision regarding which patient to receive biopsy and enabled the highest reduction rate of unnecessary biopsies. Limitations include a monocentric design and a lack of PI-RADSv2.0.
  
  
  
  The novel RMs, incorporating clinical parameters and PI-RADS, performed significantly better compared with RMs without PI-RADS and provided measurable benefit in making the decision to biopsy men at a suspicion of PC. For biopsy-naïve patients, both our RM and ERSPC-RC3 plus PI-RADSv1.0 exceeded the prediction performance compared with clinical parameters alone.
  
  
  
  Combined risk models including clinical and imaging parameters predict clinically relevant prostate cancer significantly better than clinical risk calculators and multiparametric magnetic resonance imaging alone. The risk models demonstrate a benefit in making a decision about which patient needs a biopsy and concurrently help avoid unnecessary biopsies.
authors.affiliation: Department of Urology, University Hospital Heidelberg, Heidelberg, Germany; Department of Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: j.radtke@dkfz-heidelberg.de.
authors.forename: Jan Philipp
authors.initials: JP
authors.lastname: Radtke
authors.affiliation: Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Manuel
authors.initials: M
authors.lastname: Wiesenfarth
authors.affiliation: Department of Urology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Kesch
authors.affiliation: Department of Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Martin T
authors.initials: MT
authors.lastname: Freitag
authors.affiliation: Department of Diagnostic and Interventional Radiology, University Düsseldorf, Medical Faculty, Düsseldorf, Germany.
authors.forename: Celine D
authors.initials: CD
authors.lastname: Alt
authors.affiliation: Department of Urology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Kamil
authors.initials: K
authors.lastname: Celik
authors.affiliation: Department of Urology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Distler
authors.affiliation: Institute of Pathology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Roth
authors.affiliation: Institute of Pathology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Wieczorek
authors.affiliation: Institute of Medical Biometry and Informatics, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Stock
authors.affiliation: Department of Urology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Duensing
authors.affiliation: Department of Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Matthias C
authors.initials: MC
authors.lastname: Roethke
authors.affiliation: Department of Urology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Dogu
authors.initials: D
authors.lastname: Teber
authors.affiliation: Department of Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Heinz-Peter
authors.initials: HP
authors.lastname: Schlemmer
authors.affiliation: Department of Urology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Hohenfellner
authors.affiliation: Department of Urology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Bonekamp
authors.affiliation: Department of Urology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Boris A
authors.initials: BA
authors.lastname: Hadaschik
mesh_terms: D000367:Age Factors; D000368:Aged; D001706:Biopsy; D051517:Digital Rectal Examination; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D060787:Neoplasm Grading; D009929:Organ Size; D011467:Prostate / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology*; D012372:ROC Curve; D012189:Retrospective Studies; D018570:Risk Assessment / Q000379:methods; D019564:Unnecessary Procedures
chemical_list: D017430:Prostate-Specific Antigen
keywords: European Randomised Study of Screening for Prostate Cancer; Magnetic resonance imaging; Multiparametric magnetic resonance imaging; Prostate cancer; Risk model; Risk stratification