Urological Oncology
Clinical performance of the Prostate Health Index (PHI) for the prediction of prostate cancer in obese men: data from the PROMEtheuS project, a multicentre European prospective study Alberto Abrate, Massimo Lazzeri, Giovanni Lughezzani, Nicolòmaria Buffi, Vittorio Bini*, Alexander Haese†, Alexandre de la Taille‡, Thomas McNicholas§, Joan Palou Redorta¶, Giulio M. Gadda, Giuliana Lista, Ella Kinzikeeva, Nicola Fossati, Alessandro Larcher, Paolo Dell'Oglio, Francesco Mistretta, Massimo Freschi** and Giorgio Guazzoni Division of Oncology, Unit of Urology, URI, **Department of Pathology, IRCCS Ospedale San Raffaele, Università Vita-Salute San Raffaele, Milan, *Department of Internal Medicine, University of Perugia, Perugia, Italy, †Martini-Clinic Prostate Cancer Center, University Clinic Hamburg-Eppendorf, Hamburg, Germany, ‡Department of Urology, APHP Mondor Hospital, Créteil, France, §South Bedfordshire and Hertfordshire Urological Cancer Centre, Lister Hospital, Stevenage, UK, and ¶Urologic Oncology Section of the Department of Urology and Radiology Department, Fundaciò Puigvert, Barcelona, Spain
Objectives
Results
To test serum prostate-specific antigen (PSA) isoform [-2]proPSA (p2PSA), p2PSA/free PSA (%p2PSA) and Prostate Health Index (PHI) accuracy in predicting prostate cancer in obese men and to test whether PHI is more accurate than PSA in predicting prostate cancer in obese patients.
Of the 965 patients, 383 (39.7%) were normal weight (BMI 45 years, with or without positive DRE and with suspicious PSA levels, even with previous negative biopsy. Patients’ demographic and clinical characteristics were recorded on specific requisition forms. Patients with bacterial acute prostatitis, diagnosed in the 3 months before biopsy, or subjected to previous transurethral endoscopic surgery were excluded. Furthermore, patients with chronic renal failure, marked blood protein alterations (plasma normal range 6–8 g/100 mL), haemophiliacs or those previously multiply transfused were excluded as these conditions may alter p2PSA concentration [15]. Methods Before prostate biopsy, blood was drawn to measure tPSA, free PSA (fPSA) and p2PSA levels. The samples were centrifuged within 3 h, and then frozen at −80 °C and centrally processed using an Access 2 Immunoassay System, an automated
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© 2014 The Authors BJU International © 2014 BJU International
random-access analyser that performs immunoassays on body fluid samples (Beckman Coulter, Brea, CA, USA). tPSA and fPSA were determined using Hybritech calibration. Subsequently, the clinician performed a DRE. Prostate and transition zone volume (length × height × width × π/6), and abnormalities within the prostate were evaluated by TRUS. Patients underwent TRUS-guided prostate biopsies according to a standardised extended scheme: at least 12 cores taken from the prostate peripheral portion (apex, mid-gland and base), with additional cores taken when necessary according to patient’s age, prostate volume, ultrasound abnormalities or Institutional protocols. Prostate biopsy specimens were placed in specific single-core specimen containers (10% buffered formalin), processed and evaluated at each center by an experienced genitourinary pathologist. Prostate cancer was identified and graded according to the 2005 consensus conference of the International Society of Urological Pathology definitions [16]. High-grade intraepithelial neoplasia (HGPIN) or atypical small acinar proliferation of prostate (ASAP), according to contemporary diagnostic criteria, were not considered positive for the outcome of interest, i.e. prostate cancer. Outcomes The primary outcome was to test ‘clinical validity’, by defining sensitivity, specificity and accuracy, of serum p2PSA, %p2PSA {[(p2PSA pg/mL)/(fPSA ng/mL × 1000)] × 100} and Beckman Coulter PHI [(p2PSA/fPSA) × √PSA] [11] in obese patients (BMI ≥30 kg/m2). A comparison of their performance with tPSA, fPSA and fPSA/tPSA ratio (%fPSA) for the identification of prostate cancer was also performed. The analysis was carried out according to the STAndards for the Reporting of Diagnostic accuracy studies (STARD) methodology (http://www.stard-statement.org). BMI was categorised according to the WHO and National Institutes of Health (NIH) classification: normal
Clinical performance of the Prostate Health Index (PHI) for the prediction of prostate cancer in obese men: data from the PROMEtheuS project, a multicentre European prospective study Alberto Abrate, Massimo Lazzeri, Giovanni Lughezzani, Nicolòmaria Buffi, Vittorio Bini*, Alexander Haese†, Alexandre de la Taille‡, Thomas McNicholas§, Joan Palou Redorta¶, Giulio M. Gadda, Giuliana Lista, Ella Kinzikeeva, Nicola Fossati, Alessandro Larcher, Paolo Dell'Oglio, Francesco Mistretta, Massimo Freschi** and Giorgio Guazzoni Division of Oncology, Unit of Urology, URI, **Department of Pathology, IRCCS Ospedale San Raffaele, Università Vita-Salute San Raffaele, Milan, *Department of Internal Medicine, University of Perugia, Perugia, Italy, †Martini-Clinic Prostate Cancer Center, University Clinic Hamburg-Eppendorf, Hamburg, Germany, ‡Department of Urology, APHP Mondor Hospital, Créteil, France, §South Bedfordshire and Hertfordshire Urological Cancer Centre, Lister Hospital, Stevenage, UK, and ¶Urologic Oncology Section of the Department of Urology and Radiology Department, Fundaciò Puigvert, Barcelona, Spain
Objectives
Results
To test serum prostate-specific antigen (PSA) isoform [-2]proPSA (p2PSA), p2PSA/free PSA (%p2PSA) and Prostate Health Index (PHI) accuracy in predicting prostate cancer in obese men and to test whether PHI is more accurate than PSA in predicting prostate cancer in obese patients.
Of the 965 patients, 383 (39.7%) were normal weight (BMI 45 years, with or without positive DRE and with suspicious PSA levels, even with previous negative biopsy. Patients’ demographic and clinical characteristics were recorded on specific requisition forms. Patients with bacterial acute prostatitis, diagnosed in the 3 months before biopsy, or subjected to previous transurethral endoscopic surgery were excluded. Furthermore, patients with chronic renal failure, marked blood protein alterations (plasma normal range 6–8 g/100 mL), haemophiliacs or those previously multiply transfused were excluded as these conditions may alter p2PSA concentration [15]. Methods Before prostate biopsy, blood was drawn to measure tPSA, free PSA (fPSA) and p2PSA levels. The samples were centrifuged within 3 h, and then frozen at −80 °C and centrally processed using an Access 2 Immunoassay System, an automated
538
© 2014 The Authors BJU International © 2014 BJU International
random-access analyser that performs immunoassays on body fluid samples (Beckman Coulter, Brea, CA, USA). tPSA and fPSA were determined using Hybritech calibration. Subsequently, the clinician performed a DRE. Prostate and transition zone volume (length × height × width × π/6), and abnormalities within the prostate were evaluated by TRUS. Patients underwent TRUS-guided prostate biopsies according to a standardised extended scheme: at least 12 cores taken from the prostate peripheral portion (apex, mid-gland and base), with additional cores taken when necessary according to patient’s age, prostate volume, ultrasound abnormalities or Institutional protocols. Prostate biopsy specimens were placed in specific single-core specimen containers (10% buffered formalin), processed and evaluated at each center by an experienced genitourinary pathologist. Prostate cancer was identified and graded according to the 2005 consensus conference of the International Society of Urological Pathology definitions [16]. High-grade intraepithelial neoplasia (HGPIN) or atypical small acinar proliferation of prostate (ASAP), according to contemporary diagnostic criteria, were not considered positive for the outcome of interest, i.e. prostate cancer. Outcomes The primary outcome was to test ‘clinical validity’, by defining sensitivity, specificity and accuracy, of serum p2PSA, %p2PSA {[(p2PSA pg/mL)/(fPSA ng/mL × 1000)] × 100} and Beckman Coulter PHI [(p2PSA/fPSA) × √PSA] [11] in obese patients (BMI ≥30 kg/m2). A comparison of their performance with tPSA, fPSA and fPSA/tPSA ratio (%fPSA) for the identification of prostate cancer was also performed. The analysis was carried out according to the STAndards for the Reporting of Diagnostic accuracy studies (STARD) methodology (http://www.stard-statement.org). BMI was categorised according to the WHO and National Institutes of Health (NIH) classification: normal
