title: Optimizing the clinical utility of PCA3 to diagnose prostate cancer in initial prostate biopsy.
abstract: BACKGROUND
  PCA3 has been included in a nomogram outperforming previous clinical models for the prediction of any prostate cancer (PCa) and high grade PCa (HGPCa) at the initial prostate biopsy (IBx). Our objective is to validate such IBx-specific PCA3-based nomogram. We also aim to optimize the use of this nomogram in clinical practice through the definition of risk groups.
  
  
  METHODS
  Independent external validation. Clinical and biopsy data from a contemporary cohort of 401 men with the same inclusion criteria to those used to build up the reference's nomogram in IBx. The predictive value of the nomogram was assessed by means of calibration curves and discrimination ability through the area under the curve (AUC). Clinical utility of the nomogram was analyzed by choosing thresholds points that minimize the overlapping between probability density functions (PDF) in PCa and no PCa and HGPCa and no HGPCa groups, and net benefit was assessed by decision curves.
  
  
  RESULTS
  We detect 28% of PCa and 11 % of HGPCa in IBx, contrasting to the 46 and 20% at the reference series. Due to this, there is an overestimation of the nomogram probabilities shown in the calibration curve for PCa. The AUC values are 0.736 for PCa (C.I.95%:0.68-0.79) and 0.786 for HGPCa (C.I.95%:0.71-0.87) showing an adequate discrimination ability. PDF show differences in the distributions of nomogram probabilities in PCa and not PCa patient groups. A minimization of the overlapping between these curves confirms the threshold probability of harboring PCa >30 % proposed by Hansen is useful to indicate a IBx, but a cut-off > 40% could be better in series of opportunistic screening like ours. Similar results appear in HGPCa analysis. The decision curve also shows a net benefit of 6.31% for the threshold probability of 40%.
  
  
  CONCLUSIONS
  PCA3 is an useful tool to select patients for IBx. Patients with a calculated probability of having PCa over 40% should be counseled to undergo an IBx if opportunistic screening is required.
authors.affiliation: Department of Urology, Instituto Valenciano de Oncología, C/ Prof. Beltrán Báguena 8, 46009, Valencia, Spain. jrubio@fivo.org.
authors.forename: Jose
authors.initials: J
authors.lastname: Rubio-Briones
authors.affiliation: Department of Urology, Hospital Universitario Miguel Servet, Zaragoza, Spain. aborque@comz.org.
authors.forename: Angel
authors.initials: A
authors.lastname: Borque
authors.affiliation: Escuela Universitaria Politécnica de La Almunia, Universidad de Zaragoza, Zaragoza, Spain. lmeste@unizar.es.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Esteban
authors.affiliation: Department of Urology, Instituto Valenciano de Oncología, C/ Prof. Beltrán Báguena 8, 46009, Valencia, Spain. jcasanova@fivo.org.
authors.forename: Juan
authors.initials: J
authors.lastname: Casanova
authors.affiliation: Laboratory of Molecular Biology, Instituto Valenciano de Oncología, Valencia, Spain. anfersefar@yahoo.es.
authors.forename: Antonio
authors.initials: A
authors.lastname: Fernandez-Serra
authors.affiliation: Laboratory of Molecular Biology, Instituto Valenciano de Oncología, Valencia, Spain. luisrubio.fivo@gmail.com.
authors.forename: Luis
authors.initials: L
authors.lastname: Rubio
authors.affiliation: Laboratory of Molecular Biology, Instituto Valenciano de Oncología, Valencia, Spain. i.casanova.salas@gmail.com.
authors.forename: Irene
authors.initials: I
authors.lastname: Casanova-Salas
authors.affiliation: Department of Statistical Methods, Universidad de Zaragoza, Zaragoza, Spain. gerardo@unizar.es.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Sanz
authors.affiliation: Department of Urology, Instituto Valenciano de Oncología, C/ Prof. Beltrán Báguena 8, 46009, Valencia, Spain. jldominguezescrig@hotmail.com.
authors.forename: Jose
authors.initials: J
authors.lastname: Domínguez-Escrig
authors.affiliation: Department of Urology, Instituto Valenciano de Oncología, C/ Prof. Beltrán Báguena 8, 46009, Valencia, Spain. argicollado@gmail.com.
authors.forename: Argimiro
authors.initials: A
authors.lastname: Collado
authors.affiliation: Department of Urology, Instituto Valenciano de Oncología, C/ Prof. Beltrán Báguena 8, 46009, Valencia, Spain. alvarogomezferrer@gmail.com.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Gómez-Ferrer
authors.affiliation: Department of Urology, Instituto Valenciano de Oncología, C/ Prof. Beltrán Báguena 8, 46009, Valencia, Spain. macuiborra_55@hotmail.com.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Iborra
authors.affiliation: Department of Urology, Instituto Valenciano de Oncología, C/ Prof. Beltrán Báguena 8, 46009, Valencia, Spain. ramirezbackhaus@yahoo.es.
authors.forename: Miguel
authors.initials: M
authors.lastname: Ramírez-Backhaus
authors.affiliation: Department of Statistics, University of Valencia, Valencia, Spain. paco.martinez@uv.es.
authors.forename: Francisco
authors.initials: F
authors.lastname: Martínez
authors.affiliation: Department of Pathology, Instituto Valenciano de Oncología, Valencia, Spain. acalatrava@fivo.org.
authors.forename: Ana
authors.initials: A
authors.lastname: Calatrava
authors.affiliation: Laboratory of Molecular Biology, Instituto Valenciano de Oncología, Valencia, Spain. jalopez@fivo.org.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Lopez-Guerrero
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm / Q000378:metabolism*; D015415:Biomarkers / Q000652:urine; D014408:Biomarkers, Tumor; D001706:Biopsy; D015331:Cohort Studies; D003661:Decision Support Techniques; D006801:Humans; D008297:Male; D008875:Middle Aged; D049451:Nomograms; D009929:Organ Size; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors
chemical_list: D000951:Antigens, Neoplasm; D015415:Biomarkers; D014408:Biomarkers, Tumor; C479341:prostate cancer antigen 3, human