title: A multi-institutional prospective trial in the USA confirms that the 4Kscore accurately identifies men with high-grade prostate cancer.
abstract: BACKGROUND
  The 4Kscore combines measurement of four kallikreins in blood with clinical information as a measure of the probability of significant (Gleason ≥7) prostate cancer (PCa) before prostate biopsy.
  
  
  OBJECTIVE
  To perform the first prospective evaluation of the 4Kscore in predicting Gleason ≥7 PCa in the USA.
  
  
  METHODS
  Prospective enrollment of 1012 men scheduled for prostate biopsy, regardless of prostate-specific antigen level or clinical findings, was conducted at 26 US urology centers between October 2013 and April 2014.
  
  
  METHODS
  The 4Kscore.
  
  
  METHODS
  The primary outcome was Gleason ≥7 PCa on prostate biopsy. The area under the receiver operating characteristic curve, risk calibration, and decision curve analysis (DCA) were determined, along with comparisons of probability cutoffs for reducing the number of biopsies and their impact on delaying diagnosis.
  
  
  CONCLUSIONS
  Gleason ≥7 PCa was found in 231 (23%) of the 1012 patients. The 4Kscore showed excellent calibration and demonstrated higher discrimination (AUC 0.82) and net benefit compared to a modified Prostate Cancer Prevention Trial Risk Calculator 2.0 model and standard of care (biopsy for all men) according to DCA. A possible reduction of 30-58% in the number biopsies was identified with delayed diagnosis in only 1.3-4.7% of Gleason ≥7 PCa cases, depending on the threshold used for biopsy. Pathological assessment was performed according to the standard of care at each site without centralized review.
  
  
  CONCLUSIONS
  The 4Kscore showed excellent diagnostic performance in detecting significant PCa. It is a useful tool in selecting men who have significant disease and are most likely to benefit from a prostate biopsy from men with no cancer or indolent cancer.
  
  
  RESULTS
  The 4Kscore provides each patient with an accurate and personalized measure of the risk of Gleason ≥7 cancer to aid in decision-making regarding the need for prostate biopsy.
authors.affiliation: Department of Urology, University of Miami Miller School of Medicine and Sylvestor Comprehensive Cancer Center, Miami, FL, USA. Electronic address: parekhd@med.miami.edu.
authors.forename: Dipen J
authors.initials: DJ
authors.lastname: Parekh
authors.affiliation: Department of Urology, University of Miami Miller School of Medicine and Sylvestor Comprehensive Cancer Center, Miami, FL, USA.
authors.forename: Sanoj
authors.initials: S
authors.lastname: Punnen
authors.affiliation: Department of Urology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Sjoberg
authors.affiliation: Delaware Valley Urology, Mt Laurel, NJ, USA.
authors.forename: Scott W
authors.initials: SW
authors.lastname: Asroff
authors.affiliation: First Urology, Jeffersonville, IN, USA.
authors.forename: James L
authors.initials: JL
authors.lastname: Bailen
authors.affiliation: Urology Clinics of North Texas, Dallas, TX, USA.
authors.forename: James S
authors.initials: JS
authors.lastname: Cochran
authors.affiliation: Urology Associates, Nashville, TN, USA.
authors.forename: Raoul
authors.initials: R
authors.lastname: Concepcion
authors.affiliation: Skyline Urology, Sherman Oaks, CA, USA.
authors.forename: Richard D
authors.initials: RD
authors.lastname: David
authors.affiliation: Alliance Research Centers, Laguna Hills, CA, USA.
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Deck
authors.affiliation: The Urology Group, Cincinnati, OH, USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Dumbadze
authors.affiliation: Central Ohio Urology Group, Columbus, OH, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Gambla
authors.affiliation: Atlantic Urological Associates, Daytona, FL, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Grable
authors.affiliation: Regional Urology, Shreveport, LA, USA.
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: Henderson
authors.affiliation: The Urology Center of Colorado, Denver, CO, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Karsh
authors.affiliation: Delaware Valley Urology, Voorhees, NJ, USA.
authors.forename: Evan B
authors.initials: EB
authors.lastname: Krisch
authors.affiliation: Arkansas Urology, Little Rock, AR, USA.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Langford
authors.affiliation: University of Washington, Seattle, WA, USA.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Lin
authors.affiliation: Adult and Pediatric Urology, Sarteli, MN, USA.
authors.forename: Shawn M
authors.initials: SM
authors.lastname: McGee
authors.affiliation: Manchester Urology, Manchester, NH, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Munoz
authors.affiliation: Associated Medical Professionals of NY, Syracuse, NY, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Pieczonka
authors.affiliation: Lahey Hospital and Medical Center, Burlington, MA, USA.
authors.forename: Kimberley
authors.initials: K
authors.lastname: Rieger-Christ
authors.affiliation: Urology San Antonio, San Antonio, TX, USA.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Saltzstein
authors.affiliation: Urology of Indiana, Greenwood, IN, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Scott
authors.affiliation: Atlantic Urology Clinics, Myrtle Beach, SC, USA.
authors.forename: Neal D
authors.initials: ND
authors.lastname: Shore
authors.affiliation: Lancaster Urology, Lancaster, PA, USA.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Sieber
authors.affiliation: Idaho Urologic Institute, Meridian, ID, USA.
authors.forename: Todd M
authors.initials: TM
authors.lastname: Waldmann
authors.affiliation: Skyline Urology, Torrance, CA, USA.
authors.forename: Fredrick N
authors.initials: FN
authors.lastname: Wolk
authors.affiliation: Andover Urology, Andover, MA, USA.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Zappala
mesh_terms: D000368:Aged; D019540:Area Under Curve; D062005:Biopsy, Large-Core Needle; D015331:Cohort Studies; D006801:Humans; D007610:Kallikreins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000473:pathology; D012372:ROC Curve; D012680:Sensitivity and Specificity; D020840:Tissue Kallikreins / Q000097:blood*; D014481:United States
chemical_list: C549870:KLK3 protein, human; D007610:Kallikreins; D020840:Tissue Kallikreins; D017430:Prostate-Specific Antigen
keywords: Biomarkers; Biopsy; Prostate cancer; Screening