title: Prognostic utility of the cell cycle progression score generated from biopsy in men treated with prostatectomy.
abstract: OBJECTIVE
  The cell cycle progression score is associated with prostate cancer outcomes in various clinical settings. However, previous studies of men treated with radical prostatectomy evaluated cell cycle progression scores generated from resected tumor tissue. We evaluated the prognostic usefulness of the score derived from biopsy specimens in men treated with radical prostatectomy.
  
  
  METHODS
  We evaluated the cell cycle progression score in cohorts of patients from the Martini Clinic (283), Durham Veterans Affairs Medical Center (176) and Intermountain Healthcare (123). The score was derived from simulated biopsy (Martini Clinic) or diagnostic biopsy (Durham Veterans Affairs Medical Center and Intermountain Healthcare) and evaluated for an association with biochemical recurrence and metastatic disease.
  
  
  RESULTS
  In all 3 cohorts the cell cycle progression score was associated with biochemical recurrence and metastatic disease. The association with biochemical recurrence remained significant after adjusting for other prognostic clinical variables. On combined analysis of all cohorts (total 582 patients) the score was a strong predictor of biochemical recurrence on univariate analysis (HR per score unit 1.60, 95% CI 1.35-1.90, p=2.4×10(-7)) and multivariate analysis (HR per score unit 1.47, 95% CI 1.23-1.76, p=4.7×10(-5)). Although there were few events (12), the cell cycle progression score was the strongest predictor of metastatic disease on univariate analysis (HR per score unit 5.35, 95% CI 2.89-9.92, p=2.1×10(-8)) and after adjusting for clinical variables (HR per score unit 4.19, 95% CI 2.08-8.45, p=8.2×10(-6)).
  
  
  CONCLUSIONS
  The cell cycle progression score derived from a biopsy sample was associated with adverse outcomes after surgery. These results indicate that the score can be used at disease diagnosis to better define patient prognosis and enable more appropriate clinical care.
authors: Intermountain Healthcare (JTB), Salt Lake City, Utah; Myriad Genetics, Inc. (JR, WW, ZS, ET, JP, AY, AG, JSL, MB), Salt Lake City, Utah; Department of Surgery, Durham Veterans Affairs Medical Center (SJF, LG), Durham, North Carolina; Department of Surgery (Urology) (SJF, LG), Duke University School of Medicine, Durham, North Carolina; Department of Pathology (SJF), Duke University School of Medicine, Durham, North Carolina; Martini-Clinic, Prostate Cancer Center (PT, MG), University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Institute for Pathology (GS), University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: Jay.Bishoff@imail.org.
authors: Jay T
authors: JT
authors: Bishoff
authors: Intermountain Healthcare (JTB), Salt Lake City, Utah; Myriad Genetics, Inc. (JR, WW, ZS, ET, JP, AY, AG, JSL, MB), Salt Lake City, Utah; Department of Surgery, Durham Veterans Affairs Medical Center (SJF, LG), Durham, North Carolina; Department of Surgery (Urology) (SJF, LG), Duke University School of Medicine, Durham, North Carolina; Department of Pathology (SJF), Duke University School of Medicine, Durham, North Carolina; Martini-Clinic, Prostate Cancer Center (PT, MG), University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Institute for Pathology (GS), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Stephen J
authors: SJ
authors: Freedland
authors: Intermountain Healthcare (JTB), Salt Lake City, Utah; Myriad Genetics, Inc. (JR, WW, ZS, ET, JP, AY, AG, JSL, MB), Salt Lake City, Utah; Department of Surgery, Durham Veterans Affairs Medical Center (SJF, LG), Durham, North Carolina; Department of Surgery (Urology) (SJF, LG), Duke University School of Medicine, Durham, North Carolina; Department of Pathology (SJF), Duke University School of Medicine, Durham, North Carolina; Martini-Clinic, Prostate Cancer Center (PT, MG), University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Institute for Pathology (GS), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Leah
authors: L
authors: Gerber
authors: Intermountain Healthcare (JTB), Salt Lake City, Utah; Myriad Genetics, Inc. (JR, WW, ZS, ET, JP, AY, AG, JSL, MB), Salt Lake City, Utah; Department of Surgery, Durham Veterans Affairs Medical Center (SJF, LG), Durham, North Carolina; Department of Surgery (Urology) (SJF, LG), Duke University School of Medicine, Durham, North Carolina; Department of Pathology (SJF), Duke University School of Medicine, Durham, North Carolina; Martini-Clinic, Prostate Cancer Center (PT, MG), University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Institute for Pathology (GS), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Pierre
authors: P
authors: Tennstedt
authors: Intermountain Healthcare (JTB), Salt Lake City, Utah; Myriad Genetics, Inc. (JR, WW, ZS, ET, JP, AY, AG, JSL, MB), Salt Lake City, Utah; Department of Surgery, Durham Veterans Affairs Medical Center (SJF, LG), Durham, North Carolina; Department of Surgery (Urology) (SJF, LG), Duke University School of Medicine, Durham, North Carolina; Department of Pathology (SJF), Duke University School of Medicine, Durham, North Carolina; Martini-Clinic, Prostate Cancer Center (PT, MG), University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Institute for Pathology (GS), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Julia
authors: J
authors: Reid
authors: Intermountain Healthcare (JTB), Salt Lake City, Utah; Myriad Genetics, Inc. (JR, WW, ZS, ET, JP, AY, AG, JSL, MB), Salt Lake City, Utah; Department of Surgery, Durham Veterans Affairs Medical Center (SJF, LG), Durham, North Carolina; Department of Surgery (Urology) (SJF, LG), Duke University School of Medicine, Durham, North Carolina; Department of Pathology (SJF), Duke University School of Medicine, Durham, North Carolina; Martini-Clinic, Prostate Cancer Center (PT, MG), University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Institute for Pathology (GS), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: William
authors: W
authors: Welbourn
authors: Intermountain Healthcare (JTB), Salt Lake City, Utah; Myriad Genetics, Inc. (JR, WW, ZS, ET, JP, AY, AG, JSL, MB), Salt Lake City, Utah; Department of Surgery, Durham Veterans Affairs Medical Center (SJF, LG), Durham, North Carolina; Department of Surgery (Urology) (SJF, LG), Duke University School of Medicine, Durham, North Carolina; Department of Pathology (SJF), Duke University School of Medicine, Durham, North Carolina; Martini-Clinic, Prostate Cancer Center (PT, MG), University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Institute for Pathology (GS), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Markus
authors: M
authors: Graefen
authors: Intermountain Healthcare (JTB), Salt Lake City, Utah; Myriad Genetics, Inc. (JR, WW, ZS, ET, JP, AY, AG, JSL, MB), Salt Lake City, Utah; Department of Surgery, Durham Veterans Affairs Medical Center (SJF, LG), Durham, North Carolina; Department of Surgery (Urology) (SJF, LG), Duke University School of Medicine, Durham, North Carolina; Department of Pathology (SJF), Duke University School of Medicine, Durham, North Carolina; Martini-Clinic, Prostate Cancer Center (PT, MG), University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Institute for Pathology (GS), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Zaina
authors: Z
authors: Sangale
authors: Intermountain Healthcare (JTB), Salt Lake City, Utah; Myriad Genetics, Inc. (JR, WW, ZS, ET, JP, AY, AG, JSL, MB), Salt Lake City, Utah; Department of Surgery, Durham Veterans Affairs Medical Center (SJF, LG), Durham, North Carolina; Department of Surgery (Urology) (SJF, LG), Duke University School of Medicine, Durham, North Carolina; Department of Pathology (SJF), Duke University School of Medicine, Durham, North Carolina; Martini-Clinic, Prostate Cancer Center (PT, MG), University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Institute for Pathology (GS), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Eliso
authors: E
authors: Tikishvili
authors: Intermountain Healthcare (JTB), Salt Lake City, Utah; Myriad Genetics, Inc. (JR, WW, ZS, ET, JP, AY, AG, JSL, MB), Salt Lake City, Utah; Department of Surgery, Durham Veterans Affairs Medical Center (SJF, LG), Durham, North Carolina; Department of Surgery (Urology) (SJF, LG), Duke University School of Medicine, Durham, North Carolina; Department of Pathology (SJF), Duke University School of Medicine, Durham, North Carolina; Martini-Clinic, Prostate Cancer Center (PT, MG), University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Institute for Pathology (GS), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Jimmy
authors: J
authors: Park
authors: Intermountain Healthcare (JTB), Salt Lake City, Utah; Myriad Genetics, Inc. (JR, WW, ZS, ET, JP, AY, AG, JSL, MB), Salt Lake City, Utah; Department of Surgery, Durham Veterans Affairs Medical Center (SJF, LG), Durham, North Carolina; Department of Surgery (Urology) (SJF, LG), Duke University School of Medicine, Durham, North Carolina; Department of Pathology (SJF), Duke University School of Medicine, Durham, North Carolina; Martini-Clinic, Prostate Cancer Center (PT, MG), University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Institute for Pathology (GS), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Adib
authors: A
authors: Younus
authors: Intermountain Healthcare (JTB), Salt Lake City, Utah; Myriad Genetics, Inc. (JR, WW, ZS, ET, JP, AY, AG, JSL, MB), Salt Lake City, Utah; Department of Surgery, Durham Veterans Affairs Medical Center (SJF, LG), Durham, North Carolina; Department of Surgery (Urology) (SJF, LG), Duke University School of Medicine, Durham, North Carolina; Department of Pathology (SJF), Duke University School of Medicine, Durham, North Carolina; Martini-Clinic, Prostate Cancer Center (PT, MG), University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Institute for Pathology (GS), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Alexander
authors: A
authors: Gutin
authors: Intermountain Healthcare (JTB), Salt Lake City, Utah; Myriad Genetics, Inc. (JR, WW, ZS, ET, JP, AY, AG, JSL, MB), Salt Lake City, Utah; Department of Surgery, Durham Veterans Affairs Medical Center (SJF, LG), Durham, North Carolina; Department of Surgery (Urology) (SJF, LG), Duke University School of Medicine, Durham, North Carolina; Department of Pathology (SJF), Duke University School of Medicine, Durham, North Carolina; Martini-Clinic, Prostate Cancer Center (PT, MG), University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Institute for Pathology (GS), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Jerry S
authors: JS
authors: Lanchbury
authors: Intermountain Healthcare (JTB), Salt Lake City, Utah; Myriad Genetics, Inc. (JR, WW, ZS, ET, JP, AY, AG, JSL, MB), Salt Lake City, Utah; Department of Surgery, Durham Veterans Affairs Medical Center (SJF, LG), Durham, North Carolina; Department of Surgery (Urology) (SJF, LG), Duke University School of Medicine, Durham, North Carolina; Department of Pathology (SJF), Duke University School of Medicine, Durham, North Carolina; Martini-Clinic, Prostate Cancer Center (PT, MG), University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Institute for Pathology (GS), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Guido
authors: G
authors: Sauter
authors: Intermountain Healthcare (JTB), Salt Lake City, Utah; Myriad Genetics, Inc. (JR, WW, ZS, ET, JP, AY, AG, JSL, MB), Salt Lake City, Utah; Department of Surgery, Durham Veterans Affairs Medical Center (SJF, LG), Durham, North Carolina; Department of Surgery (Urology) (SJF, LG), Duke University School of Medicine, Durham, North Carolina; Department of Pathology (SJF), Duke University School of Medicine, Durham, North Carolina; Martini-Clinic, Prostate Cancer Center (PT, MG), University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Institute for Pathology (GS), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Michael
authors: M
authors: Brawer
authors: Intermountain Healthcare (JTB), Salt Lake City, Utah; Myriad Genetics, Inc. (JR, WW, ZS, ET, JP, AY, AG, JSL, MB), Salt Lake City, Utah; Department of Surgery, Durham Veterans Affairs Medical Center (SJF, LG), Durham, North Carolina; Department of Surgery (Urology) (SJF, LG), Duke University School of Medicine, Durham, North Carolina; Department of Pathology (SJF), Duke University School of Medicine, Durham, North Carolina; Martini-Clinic, Prostate Cancer Center (PT, MG), University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Institute for Pathology (GS), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Steven
authors: S
authors: Stone
authors: Intermountain Healthcare (JTB), Salt Lake City, Utah; Myriad Genetics, Inc. (JR, WW, ZS, ET, JP, AY, AG, JSL, MB), Salt Lake City, Utah; Department of Surgery, Durham Veterans Affairs Medical Center (SJF, LG), Durham, North Carolina; Department of Surgery (Urology) (SJF, LG), Duke University School of Medicine, Durham, North Carolina; Department of Pathology (SJF), Duke University School of Medicine, Durham, North Carolina; Martini-Clinic, Prostate Cancer Center (PT, MG), University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Institute for Pathology (GS), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Thorsten
authors: T
authors: Schlomm
mesh_terms: D000368:Aged; D001707:Biopsy, Needle; D002453:Cell Cycle; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011467:Prostate / Q000473:pathology*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000601:surgery*
keywords: biopsy; prognosis; prostate; prostatectomy; prostatic neoplasms