title: Validation of a cell-cycle progression gene panel to improve risk stratification in a contemporary prostatectomy cohort.
abstract: OBJECTIVE
  We aimed to validate a previously described genetic risk score, denoted the cell-cycle progression (CCP) score, in predicting contemporary radical prostatectomy (RP) outcomes.
  
  
  METHODS
  RNA was quantified from paraffin-embedded RP specimens. The CCP score was calculated as average expression of 31 CCP genes, normalized to 15 housekeeper genes. Recurrence was defined as two prostate-specific antigen levels ≥ 0.2 ng/mL or any salvage treatment. Associations between CCP score and recurrence were examined, with adjustment for clinical and pathologic variables using Cox proportional hazards regression and partial likelihood ratio tests. The CCP score was assessed for independent prognostic utility beyond a standard postoperative risk assessment (Cancer of the Prostate Risk Assessment post-Surgical [CAPRA-S] score), and a score combining CAPRA-S and CCP was validated.
  
  
  RESULTS
  Eighty-two (19.9%) of 413 men experienced recurrence. The hazard ratio (HR) for each unit increase in CCP score (range, -1.62 to 2.16) was 2.1 (95% CI, 1.6 to 2.9); with adjustment for CAPRA-S, the HR was 1.7 (95% CI, 1.3 to 2.4). The score was able to substratify patients with low clinical risk as defined by CAPRA-S ≤ 2 (HR, 2.3; 95% CI, 1.4 to 3.7). Combining the CCP and CAPRA-S improved the concordance index for both the overall cohort and low-risk subset; the combined CAPRA-S + CCP score consistently predicted outcomes across the range of clinical risk. This combined score outperformed both individual scores on decision curve analysis.
  
  
  CONCLUSIONS
  The CCP score was validated to have significant prognostic accuracy after controlling for all available clinical and pathologic data. The score may improve accuracy of risk stratification for men with clinically localized prostate cancer, including those with low-risk disease.
authors: University of California, San Francisco, Box 1695, 1600 Divisadero St, A-624, San Francisco, CA 94143-1695, USA. mcooperberg@urology.ucsf.edu
authors: Matthew R
authors: MR
authors: Cooperberg
authors: Jeffry P
authors: JP
authors: Simko
authors: Janet E
authors: JE
authors: Cowan
authors: Julia E
authors: JE
authors: Reid
authors: Azita
authors: A
authors: Djalilvand
authors: Satish
authors: S
authors: Bhatnagar
authors: Alexander
authors: A
authors: Gutin
authors: Jerry S
authors: JS
authors: Lanchbury
authors: Gregory P
authors: GP
authors: Swanson
authors: Steven
authors: S
authors: Stone
authors: Peter R
authors: PR
authors: Carroll
mesh_terms: D000368:Aged; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics; D015331:Cohort Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000032:analysis; D011468:Prostatectomy / Q000379:methods*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000601:surgery*; D015203:Reproducibility of Results; D018570:Risk Assessment / Q000379:methods / Q000706:statistics & numerical data
chemical_list: D018797:Cell Cycle Proteins; D017430:Prostate-Specific Antigen