title: Improving the Specificity of Screening for Lethal Prostate Cancer Using Prostate-specific Antigen and a Panel of Kallikrein Markers: A Nested Case-Control Study.
abstract: BACKGROUND
  A disadvantage of prostate-specific antigen (PSA) for the early detection of prostate cancer (PCa) is that many men must be screened, biopsied, and diagnosed to prevent one death.
  
  
  OBJECTIVE
  To increase the specificity of screening for lethal PCa at an early stage.
  
  
  METHODS
  We conducted a case-control study nested within a population-based cohort. PSA and three additional kallikreins were measured in cryopreserved blood from a population-based cohort in Västerbotten, Sweden. Of 40379 men providing blood at ages 40, 50, and 60 yr from 1986 to 2009, 12542 men were followed for >15 yr. From this cohort, the Swedish Cancer Registry identified 1423 incident PCa cases, 235 with distant metastasis.
  
  
  METHODS
  Risk of distant metastasis for different PSA levels and a prespecified statistical model based on the four kallikrein markers.
  
  
  CONCLUSIONS
  Most metastatic cases occurred in men with PSA in the top quartile at age 50 yr (69%) or 60 yr (74%), whereas 20-yr risk of metastasis for men with PSA below median was low (≤0.6%). Among men with PSA >2 ng/ml, a prespecified model based on four kallikrein markers significantly enhanced the prediction of metastasis compared with PSA alone. About half of all men with PSA >2 ng/ml were defined as low risk by this model and had a ≤1% 15-yr risk of metastasis.
  
  
  CONCLUSIONS
  Screening at ages 50-60 yr should focus on men with PSA in the top quartile. A marker panel can aid biopsy decision making.
  
  
  RESULTS
  For men in their fifties, screening should focus on those in the top 10% to 25% of PSA values because the majority of subsequent cases of distant metastasis are found among these men. Testing of four kallikrein markers in men with an elevated PSA could aid biopsy decision making.
authors: Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden.
authors: Pär
authors: P
authors: Stattin
authors: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors: Andrew J
authors: AJ
authors: Vickers
authors: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors: Daniel D
authors: DD
authors: Sjoberg
authors: Regional Cancer Centre, Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
authors: Robert
authors: R
authors: Johansson
authors: Department of Urology, Sankt Göran Hospital, Stockholm, Sweden.
authors: Torvald
authors: T
authors: Granfors
authors: Section of Genetics, The International Agency for Research on Cancer, Lyon, France.
authors: Mattias
authors: M
authors: Johansson
authors: Division of Biotechnology, University of Turku, Turku, Finland.
authors: Kim
authors: K
authors: Pettersson
authors: Department of Surgery (Urology), Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors: Peter T
authors: PT
authors: Scardino
authors: Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University, Umeå, Sweden.
authors: Göran
authors: G
authors: Hallmans
authors: Department of Surgery (Urology), Memorial Sloan Kettering Cancer Center, New York, NY, USA; Departments of Laboratory Medicine and Medicine (Genitourinary Oncology), Memorial Sloan Kettering Cancer Center, New York, NY, USA; Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Headington, Oxford, UK; Department of Translational Medicine, Lund University, Skåne University Hospital, Malmö, Sweden. Electronic address: liljah@mskcc.org.
authors: Hans
authors: H
authors: Lilja
mesh_terms: D000328:Adult; D001706:Biopsy; D016022:Case-Control Studies; D003661:Decision Support Techniques; D055088:Early Detection of Cancer / Q000379:methods*; D006801:Humans; D007610:Kallikreins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D018579:Patient Selection; D011237:Predictive Value of Tests; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000401:mortality* / Q000473:pathology; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology; D013997:Time Factors; D015854:Up-Regulation
chemical_list: C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: Cancer metastasis; Kallikrein-related peptidases; Prostate biopsy; Prostate cancer; Prostate-specific antigen