title: The natural history of men treated with deferred androgen deprivation therapy in whom metastatic prostate cancer developed following radical prostatectomy.
abstract: OBJECTIVE
  We report on the natural history and factors influencing the prognosis of a cohort of hormone naïve, prostate specific antigen era patients in whom metastatic prostate cancer developed after radical prostatectomy who were followed closely and treated with deferred androgen deprivation therapy at the time of metastasis.
  
  
  METHODS
  A total of 3,096 men underwent radical prostatectomy performed by a single surgeon at Johns Hopkins Hospital between 1987 and 2005. Of these men 422 had prostate specific antigen failure. Distant metastasis developed in 123 patients, of whom 91 with complete data formed the study cohort initially treated during the prostate specific antigen era (1987 to 2005) and receiving androgen deprivation therapy after documented metastasis. A total of 41 men died of prostate cancer. Median survival times were estimated by Kaplan-Meier analysis. Prognostic impact was estimated as the hazard ratio derived from the Cox proportional hazards model.
  
  
  RESULTS
  Median followup from radical prostatectomy was 120 months (range 24 to 216). Kaplan-Meier median (range) times to failure were 24 months (12 to 144) from radical prostatectomy to prostate specific antigen failure, 36 months (0 to 132) from prostate specific antigen failure to metastasis, 84 months (12 to 180) from metastasis to death and 168 months (24 to 216) from radical prostatectomy to death. Statistically significant univariate risk factors for prostate cancer specific mortality at the time of metastasis were pain at diagnosis of metastases (p = 0.002), time from radical prostatectomy to metastasis (p = 0.024) and prostate specific antigen doubling time less than 3 months during the 24 months before metastasis (p = 0.016). Multivariable analysis demonstrated independent predictors of prostate cancer specific mortality at the time of metastasis, namely pain (HR 3.5, p = 0.003) and prostate specific antigen doubling time less than 3 months (HR 3.4, p = 0.017).
  
  
  CONCLUSIONS
  Men treated with deferred androgen deprivation therapy for the development of metastasis after radical prostatectomy may have a long life span, 169 months after radical prostatectomy (range 24 to 216). The presence of pain and short prostate specific antigen doubling time predicted an unfavorable outcome.
authors.affiliation: James Buchanan Brady Urological Institute and the Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA. dmakarov@jhmi.edu
authors.forename: Danil V
authors.initials: DV
authors.lastname: Makarov
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Humphreys
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Mangold
authors.forename: Michael A
authors.initials: MA
authors.lastname: Carducci
authors.forename: Alan W
authors.initials: AW
authors.lastname: Partin
authors.forename: Mario A
authors.initials: MA
authors.lastname: Eisenberger
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Walsh
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Trock
mesh_terms: D000328:Adult; D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000473:pathology / Q000628:therapy*; D013997:Time Factors; D017211:Treatment Failure
chemical_list: D000726:Androgen Antagonists; D017430:Prostate-Specific Antigen