title: Association between PSA kinetics and cancer-specific mortality in patients with localised prostate cancer: analysis of the placebo arm of the SPCG-6 study.
abstract: BACKGROUND
  The prognostic value of prostate-specific antigen (PSA) kinetics in untreated prostate cancer (PCa) patients is debatable. We investigated the association between PSA doubling time (PSAdt), PSA velocity (PSAvel) and PSAvel risk count (PSAvRC) and PCa mortality in a cohort of patients with localised PCa managed on watchful waiting.
  
  
  METHODS
  Patients with clinically localised PCa managed observationally, who were randomised to and remained on placebo for minimum 18 months in the SPCG-6 study, were included. All patients survived at least 2 years and had a minimum of three PSA determinations available. The prognostic value of PSA kinetics was analysed and patients were stratified according to their PSA at consent: ≤10, 10.1-25, and >25 ng/ml. Cumulative incidences of PCa-specific mortality were estimated with the Aalen-Johansen method.
  
  
  RESULTS
  Two hundred and sixty-three patients were included of which 116, 76 and 71 had a PSA at consent ≤10, 10.1-25, and >25 ng/ml, respectively. Median follow-up was 13.6 years. For patients with PSA at consent between 10.1 and 25 ng/ml, the 13-year risks of PCa mortality were associated with PSA kinetics: PSAdt ≤3 years: 62.0% versus PSAdt >3 years: 16.3% (Gray's test: P < 0.0001), PSAvel ≥2 ng/ml/year: 48.0% versus PSAvel <2 ng/ml/year: 11.0% (Gray's test: P = 0.0008), and PSAvRC 2: 45.0% versus 0-1: 3.8% (Gray's test: P = 0.001). In contrast, none of the PSA kinetics were significantly associated with changes of 13-year risks of PCa mortality in patients with PSA at consent ≤10 or >25 ng/ml.
  
  
  CONCLUSIONS
  We found that magnitude changes in 13-year risks of PCa mortality that can be indicated by PSA kinetics depend on PSA level in patients with localised PCa who were managed observationally. Our results question PSA kinetics as surrogate marker for PCa mortality in patients with low and high PSA values.
  
  
  BACKGROUND
  NCT00672282.
authors.affiliation: Copenhagen Prostate Cancer Center, Department of Urology, Rigshospitalet, University of Copenhagen, Copenhagen thomsen.frederik@gmail.com.
authors.forename: F B
authors.initials: FB
authors.lastname: Thomsen
authors.affiliation: Copenhagen Prostate Cancer Center, Department of Urology, Rigshospitalet, University of Copenhagen, Copenhagen.
authors.forename: K
authors.initials: K
authors.lastname: Brasso
authors.affiliation: Copenhagen Prostate Cancer Center, Department of Urology, Rigshospitalet, University of Copenhagen, Copenhagen.
authors.forename: K D
authors.initials: KD
authors.lastname: Berg
authors.affiliation: Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark.
authors.forename: T A
authors.initials: TA
authors.lastname: Gerds
authors.affiliation: Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
authors.forename: J-E
authors.initials: JE
authors.lastname: Johansson
authors.affiliation: Faculty of Medicine, Norwegian University of Technology and Science, Trondheim, Norway.
authors.forename: A
authors.initials: A
authors.lastname: Angelsen
authors.affiliation: Department of Surgery, Tampere University Hospital and School of Medicine, University of Tampere, Tampere, Finland.
authors.forename: T L J
authors.initials: TL
authors.lastname: Tammela
authors.affiliation: Copenhagen Prostate Cancer Center, Department of Urology, Rigshospitalet, University of Copenhagen, Copenhagen.
authors.forename: P
authors.initials: P
authors.lastname: Iversen
mesh_terms: D000368:Aged; D000813:Anilides / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000009:adverse effects / Q000627:therapeutic use*; D010919:Placebos / Q000627:therapeutic use; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood* / Q000401:mortality / Q000628:therapy*; D014105:Tosyl Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000813:Anilides; D009570:Nitriles; D010919:Placebos; D014105:Tosyl Compounds; C053541:bicalutamide; D017430:Prostate-Specific Antigen
keywords: PSA doubling time; PSA kinetic; PSA velocity; PSA velocity risk count; prostate cancer; survival