title: Predictive value of prostate specific antigen in a European HIV-positive cohort: does one size fit all?
abstract: It is common practice to use prostate specific antigen (PSA) ≥4.0 ng/ml as a clinical indicator for men at risk of prostate cancer (PCa), however, this is unverified in HIV+ men. We aimed to describe kinetics and predictive value of PSA for PCa in HIV+ men.
  
  
  
  A nested case control study of 21 men with PCa and 40 matched-controls within EuroSIDA was conducted. Prospectively stored plasma samples before PCa (or matched date in controls) were measured for the following markers: total PSA (tPSA), free PSA (fPSA), testosterone and sex hormone binding globulin (SHBG). Conditional logistic regression models investigated associations between markers and PCa. Mixed models were used to describe kinetics. Sensitivity and specificity of using tPSA >4 ng/ml to predict PCa was calculated. Receiver operating characteristic curves were used to identify optimal cutoffs in HIV+ men for total PSA.
  
  
  
  61 HIV+ men were included with a median 6 (IQR 2-9) years follow-up. Levels of tPSA increased by 13.7% per year (95% CI 10.3, 17.3) in cases, but was stable in controls (-0.4%; 95% CI -2.5, 1.7). Elevated PSA was associated with higher odds of PCa at first (OR for twofold higher 4.7; 95% CI 1.7, 12.9; P<0.01) and last sample (8.1; 95% CI 1.1, 58.9; P=0.04). A similar relationship was seen between fPSA and PCa. Testosterone and SHBG level were not associated with PCa. tPSA level >4 ng/ml had 99% specificity and 38% sensitivity. The optimal PSA cutoff was 1.5 ng/ml overall (specificity =84%, sensitivity =81%).
  
  
  
  PSA was highly predictive of PCa in HIV+ men; however, the commonly used PSA>4 ng/ml to indicate high PCa risk was not sensitive in our population and use of the lower cutoff of PSA>1.5 ng/ml warrants consideration.
authors.affiliation: Research Department of Infection and Population Health, University College London, London, UK.
authors.forename: Leah
authors.initials: L
authors.lastname: Shepherd
authors.affiliation: Centre for Health & Infectious Disease Research (CHIP), Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Álvaro H
authors.initials: ÁH
authors.lastname: Borges
authors.affiliation: Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Lene
authors.initials: L
authors.lastname: Ravn
authors.affiliation: Charing Cross Oncology Laboratory and Trophoblastic Disease Centre, Charing Cross Hospital Campus of Imperial College Healthcare National Health Service Trust, London, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Harvey
authors.affiliation: National Centre for HIV Malignancy, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Bower
authors.affiliation: Kirby Institute, The University of New South Wales, Sydney, NSW, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Grulich
authors.affiliation: Kaiser Permanente Northern California, Oakland, CA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Silverberg
authors.affiliation: Institut for Klinisk Medicin, Hvidovre Hospital, Hvidovre, Denmark.
authors.forename: Gitte
authors.initials: G
authors.lastname: Kronborg
authors.affiliation: Clinic of Infectious Disease, Luigi Sacco Hospital, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Galli
authors.affiliation: Centre for Health & Infectious Disease Research (CHIP), Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ole
authors.initials: O
authors.lastname: Kirk
authors.affiliation: Centre for Health & Infectious Disease Research (CHIP), Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Lundgren
authors.affiliation: Research Department of Infection and Population Health, University College London, London, UK.
authors.forename: Amanda
authors.initials: A
authors.lastname: Mocroft
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D015331:Cohort Studies; D005060:Europe; D006679:HIV Seropositivity / Q000097:blood* / Q000150:complications; D006801:Humans; D007610:Kallikreins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000150:complications / Q000175:diagnosis*; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000097:blood
chemical_list: D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen