title: Radiotherapy and short-term androgen deprivation for localized prostate cancer.
abstract: BACKGROUND
  It is not known whether short-term androgen-deprivation therapy (ADT) before and during radiotherapy improves cancer control and overall survival among patients with early, localized prostate adenocarcinoma.
  
  
  METHODS
  From 1994 through 2001, we randomly assigned 1979 eligible patients with stage T1b, T1c, T2a, or T2b prostate adenocarcinoma and a prostate-specific antigen (PSA) level of 20 ng per milliliter or less to radiotherapy alone (992 patients) or radiotherapy with 4 months of total androgen suppression starting 2 months before radiotherapy (radiotherapy plus short-term ADT, 987 patients). The primary end point was overall survival. Secondary end points included disease-specific mortality, distant metastases, biochemical failure (an increasing level of PSA), and the rate of positive findings on repeat prostate biopsy at 2 years.
  
  
  RESULTS
  The median follow-up period was 9.1 years. The 10-year rate of overall survival was 62% among patients receiving radiotherapy plus short-term ADT (the combined-therapy group), as compared with 57% among patients receiving radiotherapy alone (hazard ratio for death with radiotherapy alone, 1.17; P=0.03). The addition of short-term ADT was associated with a decrease in the 10-year disease-specific mortality from 8% to 4% (hazard ratio for radiotherapy alone, 1.87; P=0.001). Biochemical failure, distant metastases, and the rate of positive findings on repeat prostate biopsy at 2 years were significantly improved with radiotherapy plus short-term ADT. Acute and late radiation-induced toxic effects were similar in the two groups. The incidence of grade 3 or higher hormone-related toxic effects was less than 5%. Reanalysis according to risk showed reductions in overall and disease-specific mortality primarily among intermediate-risk patients, with no significant reductions among low-risk patients.
  
  
  CONCLUSIONS
  Among patients with stage T1b, T1c, T2a, or T2b prostate adenocarcinoma and a PSA level of 20 ng per milliliter or less, the use of short-term ADT for 4 months before and during radiotherapy was associated with significantly decreased disease-specific mortality and increased overall survival. According to post hoc risk analysis, the benefit was mainly seen in intermediate-risk, but not low-risk, men. (Funded by the National Cancer Institute; RTOG 94-08 ClinicalTrials.gov number, NCT00002597.).
authors.affiliation: Radiological Associates of Sacramento, Sacramento, CA 95816, USA. jonesc@radiological.com
authors.forename: Christopher U
authors.initials: CU
authors.lastname: Jones
authors.forename: Daniel
authors.initials: D
authors.lastname: Hunt
authors.forename: David G
authors.initials: DG
authors.lastname: McGowan
authors.forename: Mahul B
authors.initials: MB
authors.lastname: Amin
authors.forename: Michael P
authors.initials: MP
authors.lastname: Chetner
authors.forename: Deborah W
authors.initials: DW
authors.lastname: Bruner
authors.forename: Mark H
authors.initials: MH
authors.lastname: Leibenhaut
authors.forename: Siraj M
authors.initials: SM
authors.lastname: Husain
authors.forename: Marvin
authors.initials: M
authors.lastname: Rotman
authors.forename: Luis
authors.initials: L
authors.lastname: Souhami
authors.forename: Howard M
authors.initials: HM
authors.lastname: Sandler
authors.forename: William U
authors.initials: WU
authors.lastname: Shipley
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D007172:Erectile Dysfunction / Q000209:etiology; D005485:Flutamide / Q000008:administration & dosage / Q000009:adverse effects; D005500:Follow-Up Studies; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists / Q000627:therapeutic use; D017273:Goserelin / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D016729:Leuprolide / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011467:Prostate / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D011878:Radiotherapy / Q000009:adverse effects; D011879:Radiotherapy Dosage; D012306:Risk; D015996:Survival Rate
chemical_list: D000726:Androgen Antagonists; D017273:Goserelin; D007987:Gonadotropin-Releasing Hormone; D005485:Flutamide; D016729:Leuprolide