title: Addition of radiotherapy to long-term androgen deprivation in locally advanced prostate cancer: an open randomised phase 3 trial.
abstract: BACKGROUND
  Radiotherapy combined with androgen-deprivation therapy (ADT) is superior to radiotherapy alone in localised prostate cancer; however, data comparing ADT alone are somewhat limited.
  
  
  OBJECTIVE
  To compare 3-yr ADT plus radiotherapy with ADT alone in locally advanced prostate cancer patients.
  
  
  METHODS
  A multicentre randomised open controlled phase 3 trial in 264 histologically confirmed T3-4 or pT3N0M0 prostate cancer patients randomised from March 2000 to December 2003.
  
  
  METHODS
  ADT (11.25mg subcutaneous depot injection of leuprorelin every 3 mo for 3 yr) plus external-beam radiotherapy or ADT alone. Flutamide (750 g/d) was administered for 1 mo.
  
  
  METHODS
  The primary objective was 5 yr progression-free survival (PFS) according to clinical or biologic criteria, using the American Society for Therapeutic Radiology and Oncology (ASTRO) and the newer (Phoenix) definition (nadir plus 2 ng/ml), by intention to treat. Secondary objectives included time to locoregional recurrence and distant metastases, and overall and disease-specific survival. Our Analyses: intent-to-treat analysis, multivariate analyses using a Cox model with a 5% threshold from univariate analysis, and Kaplan-Meier estimates.
  
  
  CONCLUSIONS
  ADT alone was administered to 130 patients and combined therapy to 133. With a median follow-up of 67 mo, 5-yr PFS was 60.9% for combined therapy versus 8.5% with ADT alone (ASTRO; p<0.0001), and 64.7% versus 15.4%, respectively, for Phoenix (p<0.0011). Locoregional progression was reported in 9.8% of combined-therapy patients versus 29.2% with ADT alone (p<0.0001) and metastatic progression in 3.0% versus 10.8%, respectively (p<0.018). Overall survival was 71.4% with combined therapy versus 71.5% with ADT alone; disease-specific survival was 93.2% versus 86.2%. Limitations included the relatively small population and a relatively short follow-up period.
  
  
  CONCLUSIONS
  Combined therapy strongly favoured improved PFS, locoregional control, and metastasis-free survival. Longer follow-up is needed to assess the potential survival impact.
authors.affiliation: Department of Urology, University Hospital, St. Etienne, France. nicolas.mottet@wanadoo.fr
authors.forename: Nicolas
authors.initials: N
authors.lastname: Mottet
authors.forename: Michel
authors.initials: M
authors.lastname: Peneau
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Mazeron
authors.forename: Vincent
authors.initials: V
authors.lastname: Molinie
authors.forename: Pierre
authors.initials: P
authors.lastname: Richaud
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D059248:Chemoradiotherapy; D018572:Disease-Free Survival; D004359:Drug Therapy, Combination; D005485:Flutamide / Q000627:therapeutic use*; D006801:Humans; D016729:Leuprolide / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D005485:Flutamide; D017430:Prostate-Specific Antigen; D016729:Leuprolide