title: Age-specific reference range of prostate-specific antigen and prostate cancer detection in population-based screening cohort in Japan: verification of Japanese Urological Association Guideline for prostate cancer.
abstract: OBJECTIVE
  To investigate the age-specific reference range of prostate-specific antigen and clinical characteristics of screening-detected cancer in prostate-specific antigen-based screening, and to verify the age-specific prostate-specific antigen cut-offs in the Japanese Urological Association Guidelines.
  
  
  METHODS
  Prostate-specific antigen distributions were estimated in a total of 69,028 screening tests according to the age of the participants in population screening from 2000 to 2013. The age-specific reference range of prostate-specific antigen for detection of cancer was investigated by analyzing the receiver operating characteristic curves. Furthermore, the clinicopathological features of screening-detected cancer with serum prostate-specific antigen levels below the age-specific prostate-specific antigen cut-off in the Japanese Urological Association Guidelines were also investigated.
  
  
  RESULTS
  Of all 69,028 screens, 2053 prostate biopsies (2.97%) were carried out and 549 cases of cancer (0.79%) were diagnosed. The 95th percentiles in all participants aged 54-59, 60-64, 65-69 and 70-75 years old were 2.90, 3.60, 4.10, and 4.70 ng/mL, respectively. The optimal prostate-specific antigen cut-offs for cancer detection determined from the receiver operating characteristic curves were 2.3 and 2.6 for the age ranges 54-69 and 70-75 years, respectively. These values were lower than the age-specific cut-offs in the Japanese Urological Association Guidelines. Of all 137 patients with prostate-specific antigen levels below the age-specific cut-offs in the Japanese Urological Association Guidelines, 80 (58.4%) had unfavorable clinicopathological features as active surveillance criteria.
  
  
  CONCLUSIONS
  The age-specific reference range of prostate-specific antigen might be lower than that recommended in the Japanese Urological Association Guidelines. An individualized and natural history-adjusted screening system should be established for screening participants with low prostate-specific antigen level.
authors.affiliation: Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan.
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Kitagawa
authors.forename: Kouji
authors.initials: K
authors.lastname: Izumi
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Sawada
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mizokami
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Nakashima
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Koshida
authors.forename: Takao
authors.initials: T
authors.lastname: Nakashima
authors.forename: Kimiomi
authors.initials: K
authors.lastname: Miyazaki
authors.forename: Mikio
authors.initials: M
authors.lastname: Namiki
mesh_terms: D000367:Age Factors; D000368:Aged; D006801:Humans; D007564:Japan; D007610:Kallikreins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D017410:Practice Guidelines as Topic; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis*; D012016:Reference Values; D012189:Retrospective Studies
chemical_list: C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: age-specific prostate-specific antigen reference range; population screening; prostate cancer