title: Predictors of castration-resistant prostate cancer after dose-escalated external beam radiotherapy.
abstract: BACKGROUND
  Castration-resistant prostate cancer (CRPC) is a near uniformly fatal form of prostate cancer; however, information on time to development and predictors for progression to CRPC is limited. We report a detailed longitudinal study for development of CRPC in men initially treated with external beam radiotherapy (EBRT).
  
  
  METHODS
  During 1991-2008, 2,478 patients with clinically localized prostate cancer were treated with dose-escalated EBRT at a single institution. The primary objective was to determine predictors of CRPC among men who failed definitive EBRT and progressed to salvage androgen-deprivation therapy (ADT). CRPC was defined as castrate levels of testosterone (<50 ng/dl) with progressive biochemical or radiographic disease.
  
  
  RESULTS
  For the entire cohort (n = 2,478), the 10-year cumulative incidence rate for developing CRPC was 9.9%. For those that progressed to salvage ADT (n = 362), the 7-year cumulative incidence rates for developing CRPC from time of salvage ADT was 33.7%. Amongst this cohort, multivariable analysis demonstrated that PSA doubling-time (continuous; hazard ratio [HR], 0.98 [0.97-0.99], P < 0.001), higher Gleason score (HR, 1.96 [1.12-3.43]; P = 0.034), and duration of ADT at time of EBRT (continuous; HR, 1.02 [1.01-1.03]; P = 0.007) were associated with development of CRPC.
  
  
  CONCLUSIONS
  This represents the first report of predictors of CRPC for patients treated with modern dose-escalated EBRT. We demonstrate that among the minority of patients not initially cured after EBRT, those treated with longer-course ADT have higher rates of resistance to the re-introduction of ADT. Future trials will need to test this subgroup with more aggressive or alternative forms of salvage therapies.
authors.affiliation: Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Spratt
authors.forename: Zachary S
authors.initials: ZS
authors.lastname: Zumsteg
authors.forename: Xin
authors.initials: X
authors.lastname: Pei
authors.forename: Paul B
authors.initials: PB
authors.lastname: Romesser
authors.forename: Josh
authors.initials: J
authors.lastname: Yamada
authors.forename: Marisa A
authors.initials: MA
authors.lastname: Kollmeier
authors.forename: Kaitlin
authors.initials: K
authors.lastname: Woo
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhang
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Zelefsky
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000532:radiotherapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D064129:Prostatic Neoplasms, Castration-Resistant / Q000175:diagnosis* / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D012189:Retrospective Studies
keywords: androgen deprivation therapy; castration resistant prostate cancer; radiotherapy