title: Intermittent androgen suppression for rising PSA level after radiotherapy.
abstract: BACKGROUND
  Intermittent androgen deprivation for prostate-specific antigen (PSA) elevation after radiotherapy may improve quality of life and delay hormone resistance. We assessed overall survival with intermittent versus continuous androgen deprivation in a noninferiority randomized trial.
  
  
  METHODS
  We enrolled patients with a PSA level greater than 3 ng per milliliter more than 1 year after primary or salvage radiotherapy for localized prostate cancer. Intermittent treatment was provided in 8-month cycles, with nontreatment periods determined according to the PSA level. The primary end point was overall survival. Secondary end points included quality of life, time to castration-resistant disease, and duration of nontreatment intervals.
  
  
  RESULTS
  Of 1386 enrolled patients, 690 were randomly assigned to intermittent therapy and 696 to continuous therapy. Median follow-up was 6.9 years. There were no significant between-group differences in adverse events. In the intermittent-therapy group, full testosterone recovery occurred in 35% of patients, and testosterone recovery to the trial-entry threshold occurred in 79%. Intermittent therapy provided potential benefits with respect to physical function, fatigue, urinary problems, hot flashes, libido, and erectile function. There were 268 deaths in the intermittent-therapy group and 256 in the continuous-therapy group. Median overall survival was 8.8 years in the intermittent-therapy group versus 9.1 years in the continuous-therapy group (hazard ratio for death, 1.02; 95% confidence interval, 0.86 to 1.21). The estimated 7-year cumulative rates of disease-related death were 18% and 15% in the two groups, respectively (P=0.24).
  
  
  CONCLUSIONS
  Intermittent androgen deprivation was noninferior to continuous therapy with respect to overall survival. Some quality-of-life factors improved with intermittent therapy. (Funded by the Canadian Cancer Society Research Institute and others; ClinicalTrials.gov number, NCT00003653.).
authors.affiliation: British Columbia Cancer Agency, Cancer Centre for the Southern Interior, 399 Royal Ave., Kelowna, BC V1Y 5L3, Canada. jcrook@bccancer.bc.ca
authors.forename: Juanita M
authors.initials: JM
authors.lastname: Crook
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: O'Callaghan
authors.forename: Graeme
authors.initials: G
authors.lastname: Duncan
authors.forename: David P
authors.initials: DP
authors.lastname: Dearnaley
authors.forename: Celestia S
authors.initials: CS
authors.lastname: Higano
authors.forename: Eric M
authors.initials: EM
authors.lastname: Horwitz
authors.forename: Eliot
authors.initials: E
authors.lastname: Frymire
authors.forename: Shawn
authors.initials: S
authors.lastname: Malone
authors.forename: Joseph
authors.initials: J
authors.lastname: Chin
authors.forename: Abdenour
authors.initials: A
authors.lastname: Nabid
authors.forename: Padraig
authors.initials: P
authors.lastname: Warde
authors.forename: Thomas
authors.initials: T
authors.lastname: Corbett
authors.forename: Steve
authors.initials: S
authors.lastname: Angyalfi
authors.forename: S Larry
authors.initials: SL
authors.lastname: Goldenberg
authors.forename: Mary K
authors.initials: MK
authors.lastname: Gospodarowicz
authors.forename: Fred
authors.initials: F
authors.lastname: Saad
authors.forename: John P
authors.initials: JP
authors.lastname: Logue
authors.forename: Emma
authors.initials: E
authors.lastname: Hall
authors.forename: Paul F
authors.initials: PF
authors.lastname: Schellhammer
authors.forename: Keyue
authors.initials: K
authors.lastname: Ding
authors.forename: Laurence
authors.initials: L
authors.lastname: Klotz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant; D004334:Drug Administration Schedule; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy; D011788:Quality of Life; D013739:Testosterone / Q000097:blood
chemical_list: D000726:Androgen Antagonists; D013739:Testosterone; D017430:Prostate-Specific Antigen