title: Preoperative Prostate-specific Antigen Isoform p2PSA and Its Derivatives, %p2PSA and Prostate Health Index, Predict Pathologic Outcomes in Patients Undergoing Radical Prostatectomy for Prostate Cancer: Results from a Multicentric European Prospective Study.
abstract: BACKGROUND
  Currently available predictive models fail to assist clinical decision making in prostate cancer (PCa) patients who are potential candidates for radical prostatectomy (RP). New biomarkers would be welcome.
  
  
  OBJECTIVE
  To test the hypothesis that prostate-specific antigen (PSA) isoform p2PSA and its derivatives, percentage of p2PSA to free PSA (%p2PSA) and the Prostate Health Index (PHI), predict PCa characteristics at final pathology.
  
  
  METHODS
  An observational prospective multicentre European study was performed in 489 consecutive PCa patients treated with RP. Total PSA (tPSA), free PSA (fPSA), and p2PSA levels were determined. The %fPSA [(fPSA / tPSA) × 100], %p2PSA [(p2PSA pg/ml) / (fPSA ng/ml × 1000) × 100], and PHI [(p2PSA / fPSA) × √tPSA] were calculated.
  
  
  METHODS
  Open or robot-assisted RP.
  
  
  METHODS
  Logistic regression models were fitted to test the predictors of pT3 stage and/or pathologic Gleason score (GS) ≥7 and to determine their predictive accuracy. The base multivariable model included tPSA, digital rectal examination, biopsy GS, and percentage of positive biopsy cores. Decision curve analysis provided an estimate of the net benefit obtained using p2PSA, %p2PSA, or PHI.
  
  
  CONCLUSIONS
  Overall, 344 patients (70%) were affected by pT3 disease or pathologic GS ≥7; pT3 disease and pathologic GS ≥7 were present in 126 patients (26%). At univariable analysis, p2PSA, %p2PSA, and PHI were significant predictors of pT3 disease and/or pathologic GS ≥7 (all p ≤ 0.001). The inclusion of PHI significantly increased the accuracy of the base multivariable model by 2.3% (p=0.003) and 2.4% (p=0.01) for the prediction of pT3 disease and/or pathologic GS ≥7, respectively. However, at decision curve analysis, models including PHI did not show evidence of a greater clinical net benefit.
  
  
  CONCLUSIONS
  Both %p2PSA and PHI are significant predictors of unfavourable PCa characteristics at final pathology; however, %p2PSA and PHI did not provide a greater net benefit for clinical decision making.
  
  
  RESULTS
  Prostate-specific antigen (PSA) isoform p2PSA and its derivatives, percentage of p2PSA to free PSA and the Prostate Health Index, are associated with adverse characteristics of prostate cancer; however, these biomarkers provided only a slight net benefit for clinical decision making.
authors.affiliation: Division of Oncology / Unit of Urology, IRCCS Ospedale San Raffaele - Ville Turro, Vita-Salute San Raffaele University, Milan, Italy. Electronic address: nicola.fossati@gmail.com.
authors.forename: Nicola
authors.initials: N
authors.lastname: Fossati
authors.affiliation: Division of Oncology / Unit of Urology, IRCCS Ospedale San Raffaele - Ville Turro, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Nicolò Maria
authors.initials: NM
authors.lastname: Buffi
authors.affiliation: Martini-Clinic Prostate Cancer Centre, University Clinic Hamburg, Eppendorf Hamburg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Haese
authors.affiliation: Department of Urology, University Hospital Charité, Berlin, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Stephan
authors.affiliation: Division of Oncology / Unit of Urology, IRCCS Ospedale San Raffaele - Ville Turro, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Larcher
authors.affiliation: South Bedfordshire & Hertfordshire Urological Cancer Centre, Lister Hospital, Stevenage, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: McNicholas
authors.affiliation: Department of Urology, APHP Mondor Hospital, Créteil, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: de la Taille
authors.affiliation: Department of Pathology, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Freschi
authors.affiliation: Division of Oncology / Unit of Urology, IRCCS Ospedale San Raffaele - Ville Turro, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Lughezzani
authors.affiliation: Division of Oncology / Unit of Urology, IRCCS Ospedale San Raffaele - Ville Turro, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Abrate
authors.affiliation: Department of Internal Medicine, University of Perugia, Perugia, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Bini
authors.affiliation: Urologic Oncology Section of the Department of Urology and Radiology Department, Fundació Puigvert, Cartagena, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Palou Redorta
authors.affiliation: Martini-Clinic Prostate Cancer Centre, University Clinic Hamburg, Eppendorf Hamburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Graefen
authors.affiliation: Division of Oncology / Unit of Urology, IRCCS Ospedale San Raffaele - Ville Turro, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Guazzoni
authors.affiliation: Division of Oncology / Unit of Urology, IRCCS Ospedale San Raffaele - Ville Turro, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Lazzeri
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015331:Cohort Studies; D006801:Humans; D007610:Kallikreins / Q000378:metabolism; D016015:Logistic Models; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000378:metabolism*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D011498:Protein Precursors / Q000378:metabolism*
chemical_list: C583834:(-2)pro-prostate-specific antigen, human; D014408:Biomarkers, Tumor; D011498:Protein Precursors; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: Biomarkers; Pathologic outcomes; Predictive models; Prostate Health Index; Prostate cancer; p2PSA