Short-term neoadjuvant androgen deprivation and radiotherapy for locally advanced prostate cancer: 10-year data from the TROG 96.01 randomised trial.

Author(s): Denham JW, Steigler A, Lamb DS, Joseph D, Turner S, Matthews J, Atkinson C, North J, Christie D, Spry NA, Tai KH, Wynne C, D'Este C

Affiliation(s): School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia. Jim.Denham@newcastle.edu.au

Publication date & source: 2011-05, Lancet Oncol., 12(5):451-9.

Publication type: Randomized Controlled Trial; Research Support, Non-U.S. Gov't

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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: Australian Government National Health and Medical Research Council, Hunter Medical Research Institute, AstraZeneca, and Schering-Plough. Copyright (c) 2011 Elsevier Ltd. All rights reserved.