title: Radical prostatectomy vs radiation therapy and androgen-suppression therapy in high-risk prostate cancer.
abstract: What's known on the subject? and What does the study add? Prostate cancer is generally considered to be high risk when the prostate-specific antigen (PSA) concentration is >20 ng/mL, the Gleason score is ≥8 or the American Joint Commission on Cancer (AJCC) tumour (T) category is ≥2c. There is no consensus on the best treatment for men with prostate cancer that includes these high-risk features. Options include external beam radiation therapy (EBRT) with androgen suppression therapy (AST), treatment with a combination of brachytherapy, EBRT and AST termed combined-modality therapy (CMT) or radical prostatectomy (RP) followed by adjuvant RT in cases where there are unfavourable pathological features, e.g. positive surgical margin, extracapsular extension and seminal vesicle invasion. While outcomes for both approaches have been published independently these treatments have not been compared in the setting of a prospective RCT where confounding factors related to patient selection for RP or CMT would be minimised. These factors include age, known prostate cancer prognostic factors and comorbidity. RCTs that compare RP to radiation-based regimens have been attempted but failed to accrue.
  
  
  OBJECTIVE
  To assess the risk of prostate cancer-specific mortality after therapy with radical prostatectomy (RP) or combined-modality therapy (CMT) with brachytherapy, external beam radiation therapy (EBRT) and androgen-suppression therapy (AST) in men with Gleason score 8-10 prostate cancer.
  
  
  METHODS
  Men with localised high-risk prostate cancer based on a Gleason score of 8-10 were selected for study from Duke University (285 men), treated between January 1988 and October 2008 with RP or from the Chicago Prostate Cancer Center or within the 21st Century Oncology establishment (372) treated between August 1991 and November 2005 with CMT. Fine and Gray multivariable regression was used to assess whether the risk of prostate cancer-specific mortality differed after RP as compared with CMT adjusting for age, cardiac comorbidity and year of treatment, and known prostate cancer prognostic factors.
  
  
  RESULTS
  As of January 2009, with a median (interquartile range) follow-up of 4.62 (2.4-8.2) years, there were 21 prostate cancer-specific deaths. Treatment with RP was not associated with an increased risk of prostate cancer-specific mortality compared with CMT (adjusted hazard ratio [HR] 1.8, 95% confidence interval [CI] 0.6-5.6, P = 0.3). Factors associated with an increased risk of prostate cancer-specific mortality were a PSA concentration of <4 ng/mL (adjusted HR 6.1, 95% CI 2.3-16, P < 0.001) as compared with ≥4 ng/mL, and clinical category T2b, c (adjusted HR 2.9; 95% CI 1.1-7.2; P = 0.03) as compared with T1c, 2a.
  
  
  CONCLUSIONS
  Initial treatment with RP as compared with CMT was not associated with an increased risk of prostate cancer-specific mortality in men with Gleason score 8-10 prostate cancer.
authors.affiliation: Dana-Farber Cancer Institute, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. kwestover@partners.org
authors.forename: Kenneth
authors.initials: K
authors.lastname: Westover
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Chen
authors.forename: Judd
authors.initials: J
authors.lastname: Moul
authors.forename: Cary
authors.initials: C
authors.lastname: Robertson
authors.forename: Thomas
authors.initials: T
authors.lastname: Polascik
authors.forename: Daniel
authors.initials: D
authors.lastname: Dosoretz
authors.forename: Michael
authors.initials: M
authors.lastname: Katin
authors.forename: Sharon
authors.initials: S
authors.lastname: Salenius
authors.forename: Anthony V
authors.initials: AV
authors.lastname: D'Amico
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001918:Brachytherapy; D003131:Combined Modality Therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000401:mortality / Q000628:therapy*; D015996:Survival Rate
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal