title: Short-term neoadjuvant androgen deprivation and radiotherapy for locally advanced prostate cancer: 10-year data from the TROG 96.01 randomised trial.
abstract: BACKGROUND
  The TROG 96.01 trial assessed whether 3-month and 6-month short-term neoadjuvant androgen deprivation therapy (NADT) decreases clinical progression and mortality after radiotherapy for locally advanced prostate cancer. Here we report the 10-year results.
  
  
  METHODS
  Between June, 1996, and February, 2000, 818 men with T2b, T2c, T3, and T4 N0 M0 prostate cancers were randomly assigned to receive radiotherapy alone, 3 months of NADT plus radiotherapy, or 6 months of NADT plus radiotherapy. The radiotherapy dose for all groups was 66 Gy, delivered to the prostate and seminal vesicles (excluding pelvic nodes) in 33 fractions of 2 Gy per day (excluding weekends) over 6·5-7·0 weeks. NADT consisted of 3·6 mg goserelin given subcutaneously every month and 250 mg flutamide given orally three times a day. NADT began 2 months before radiotherapy for the 3-month NADT group and 5 months before radiotherapy for the 6-month NADT group. Primary endpoints were prostate-cancer-specific mortality and all-cause mortality. Treatment allocation was open label and randomisation was done with a minimisation technique according to age, clinical stage, tumour grade, and initial prostate-specific antigen concentration (PSA). Analysis was by intention-to-treat. The trial has been closed to follow-up and all main endpoint analyses are completed. The trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12607000237482.
  
  
  RESULTS
  802 men were eligible for analysis (270 in the radiotherapy alone group, 265 in the 3-month NADT group, and 267 in the 6-month NADT group) after a median follow-up of 10·6 years (IQR 6·9-11·6). Compared with radiotherapy alone, 3 months of NADT decreased the cumulative incidence of PSA progression (adjusted hazard ratio 0·72, 95% CI 0·57-0·90; p=0·003) and local progression (0·49, 0·33-0·73; p=0·0005), and improved event-free survival (0·63, 0·52-0·77; p<0·0001). 6 months of NADT further reduced PSA progression (0·57, 0·46-0·72; p<0·0001) and local progression (0·45, 0·30-0·66; p=0·0001), and led to a greater improvement in event-free survival (0·51, 0·42-0·61, p<0·0001), compared with radiotherapy alone. 3-month NADT had no effect on distant progression (0·89, 0·60-1·31; p=0·550), prostate cancer-specific mortality (0·86, 0·60-1·23; p=0·398), or all-cause mortality (0·84, 0·65-1·08; p=0·180), compared with radiotherapy alone. By contrast, 6-month NADT decreased distant progression (0·49, 0·31-0·76; p=0·001), prostate cancer-specific mortality (0·49, 0·32-0·74; p=0·0008), and all-cause mortality (0·63, 0·48-0·83; p=0·0008), compared with radiotherapy alone. Treatment-related morbidity was not increased with NADT within the first 5 years after randomisation.
  
  
  CONCLUSIONS
  6 months of neoadjuvant androgen deprivation combined radiotherapy is an effective treatment option for locally advanced prostate cancer, particularly in men without nodal metastases or pre-existing metabolic comorbidities that could be exacerbated by prolonged androgen deprivation.
  
  
  BACKGROUND
  Australian Government National Health and Medical Research Council, Hunter Medical Research Institute, AstraZeneca, and Schering-Plough.
authors: School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia. Jim.Denham@newcastle.edu.au
authors: James W
authors: JW
authors: Denham
authors: Allison
authors: A
authors: Steigler
authors: David S
authors: DS
authors: Lamb
authors: David
authors: D
authors: Joseph
authors: Sandra
authors: S
authors: Turner
authors: John
authors: J
authors: Matthews
authors: Chris
authors: C
authors: Atkinson
authors: John
authors: J
authors: North
authors: David
authors: D
authors: Christie
authors: Nigel A
authors: NA
authors: Spry
authors: Keen-Hun
authors: KH
authors: Tai
authors: Chris
authors: C
authors: Wynne
authors: Catherine
authors: C
authors: D'Este
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001315:Australia; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005485:Flutamide / Q000008:administration & dosage; D005500:Follow-Up Studies; D017273:Goserelin / Q000008:administration & dosage; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D009367:Neoplasm Staging; D009520:New Zealand; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D018714:Radiotherapy, Adjuvant; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D017273:Goserelin; D005485:Flutamide