title: Validation of an RNA cell cycle progression score for predicting death from prostate cancer in a conservatively managed needle biopsy cohort.
abstract: BACKGROUND
  The natural history of prostate cancer is highly variable and difficult to predict accurately. Better markers are needed to guide management and avoid unnecessary treatment. In this study, we validate the prognostic value of a cell cycle progression score (CCP score) independently and in a prespecified linear combination with standard clinical variables, that is, a clinical-cell-cycle-risk (CCR) score.
  
  
  METHODS
  Paraffin sections from 761 men with clinically localized prostate cancer diagnosed by needle biopsy and managed conservatively in the United Kingdom, mostly between 2000 and 2003. The primary end point was prostate cancer death. Clinical variables consisted of centrally reviewed Gleason score, baseline PSA level, age, clinical stage, and extent of disease; these were combined into a single predefined risk assessment (CAPRA) score. Full data were available for 585 men who formed a fully independent validation cohort.
  
  
  RESULTS
  In univariate analysis, the CCP score hazard ratio was 2.08 (95% CI (1.76, 2.46), P<10(-13)) for one unit change of the score. In multivariate analysis including CAPRA, the CCP score hazard ratio was 1.76 (95% CI (1.44, 2.14), P<10(-6)). The predefined CCR score was highly predictive, hazard ratio 2.17 (95% CI (1.83, 2.57), χ(2)=89.0, P<10(-20)) and captured virtually all available prognostic information.
  
  
  CONCLUSIONS
  The CCP score provides significant pretreatment prognostic information that cannot be provided by clinical variables and is useful for determining which patients can be safely managed conservatively, avoiding radical treatment.
authors.affiliation: Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Cuzick
authors.affiliation: Myriad Genetics, Inc., Salt Lake City, UT, USA.
authors.forename: S
authors.initials: S
authors.lastname: Stone
authors.affiliation: Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK.
authors.forename: G
authors.initials: G
authors.lastname: Fisher
authors.affiliation: Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK.
authors.forename: Z H
authors.initials: ZH
authors.lastname: Yang
authors.affiliation: Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK.
authors.forename: B V
authors.initials: BV
authors.lastname: North
authors.affiliation: Department of Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK.
authors.forename: D M
authors.initials: DM
authors.lastname: Berney
authors.affiliation: Department of Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK.
authors.forename: L
authors.initials: L
authors.lastname: Beltran
authors.affiliation: National Cancer Registration Service (Eastern Office), Public Health England, Cambridge, UK.
authors.forename: D
authors.initials: D
authors.lastname: Greenberg
authors.affiliation: Cancer Epidemiology and Population Health, King's College London, London, UK.
authors.forename: H
authors.initials: H
authors.lastname: Møller
authors.affiliation: Myriad Genetics, Inc., Salt Lake City, UT, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Reid
authors.affiliation: Myriad Genetics, Inc., Salt Lake City, UT, USA.
authors.forename: A
authors.initials: A
authors.lastname: Gutin
authors.affiliation: Myriad Genetics, Inc., Salt Lake City, UT, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Lanchbury
authors.affiliation: Myriad Genetics, Inc., Salt Lake City, UT, USA.
authors.forename: M
authors.initials: M
authors.lastname: Brawer
authors.affiliation: Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: P
authors.initials: P
authors.lastname: Scardino
mesh_terms: D000328:Adult; D000368:Aged; D001707:Biopsy, Needle; D002453:Cell Cycle / Q000235:genetics*; D015331:Cohort Studies; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000097:blood / Q000401:mortality* / Q000473:pathology* / Q000601:surgery*; D012313:RNA / Q000235:genetics; D012107:Research Design
chemical_list: D012313:RNA