title: Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomised, phase 3 trial.
abstract: BACKGROUND
  Whether the addition of radiation therapy (RT) improves overall survival in men with locally advanced prostate cancer managed with androgen deprivation therapy (ADT) is unclear. Our aim was to compare outcomes in such patients with locally advanced prostate cancer.
  
  
  METHODS
  Patients with: locally advanced (T3 or T4) prostate cancer (n=1057); or organ-confined disease (T2) with either a prostate-specific antigen (PSA) concentration more than 40 ng/mL (n=119) or PSA concentration more than 20 ng/mL and a Gleason score of 8 or higher (n=25), were randomly assigned (done centrally with stratification and dynamic minimisation, not masked) to receive lifelong ADT and RT (65-69 Gy to the prostate and seminal vesicles, 45 Gy to the pelvic nodes). The primary endpoint was overall survival. The results presented here are of an interim analysis planned for when two-thirds of the events for the final analysis were recorded. All efficacy analyses were done by intention to treat and were based on data from all patients. This trial is registered at controlledtrials.com as ISRCTN24991896 and Clinicaltrials.gov as NCT00002633.
  
  
  RESULTS
  Between 1995 and 2005, 1205 patients were randomly assigned (602 in the ADT only group and 603 in the ADT and RT group); median follow-up was 6·0 years (IQR 4·4-8·0). At the time of analysis, a total of 320 patients had died, 175 in the ADT only group and 145 in the ADT and RT group. The addition of RT to ADT improved overall survival at 7 years (74%, 95% CI 70-78 vs 66%, 60-70; hazard ratio [HR] 0·77, 95% CI 0·61-0·98, p=0·033). Both toxicity and health-related quality-of-life results showed a small effect of RT on late gastrointestinal toxicity (rectal bleeding grade >3, three patients (0·5%) in the ADT only group, two (0·3%) in the ADT and RT group; diarrhoea grade >3, four patients (0·7%) vs eight (1·3%); urinary toxicity grade >3, 14 patients (2·3%) in both groups).
  
  
  CONCLUSIONS
  The benefits of combined modality treatment--ADT and RT--should be discussed with all patients with locally advanced prostate cancer.
  
  
  BACKGROUND
  Canadian Cancer Society Research Institute, US National Cancer Institute, and UK Medical Research Council.
authors: Princess Margaret Hospital, Toronto, Canada. padraig.warde@rmp.uhn.on.ca
authors: Padraig
authors: P
authors: Warde
authors: Malcolm
authors: M
authors: Mason
authors: Keyue
authors: K
authors: Ding
authors: Peter
authors: P
authors: Kirkbride
authors: Michael
authors: M
authors: Brundage
authors: Richard
authors: R
authors: Cowan
authors: Mary
authors: M
authors: Gospodarowicz
authors: Karen
authors: K
authors: Sanders
authors: Edmund
authors: E
authors: Kostashuk
authors: Greg
authors: G
authors: Swanson
authors: Jim
authors: J
authors: Barber
authors: Andrea
authors: A
authors: Hiltz
authors: Mahesh K B
authors: MK
authors: Parmar
authors: Jinka
authors: J
authors: Sathya
authors: John
authors: J
authors: Anderson
authors: Charles
authors: C
authors: Hayter
authors: John
authors: J
authors: Hetherington
authors: Matthew R
authors: MR
authors: Sydes
authors: Wendy
authors: W
authors: Parulekar
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000532:radiotherapy / Q000628:therapy*; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006801:Humans; D008297:Male; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000401:mortality / Q000532:radiotherapy / Q000628:therapy*; D011788:Quality of Life; D011878:Radiotherapy / Q000009:adverse effects; D015996:Survival Rate
chemical_list: D000726:Androgen Antagonists; D007987:Gonadotropin-Releasing Hormone