Short-term androgen deprivation and radiotherapy for locally advanced prostate cancer: results from the Trans-Tasman Radiation Oncology Group 96.01 randomised controlled trial

Summary Background Androgen deprivation is an established treatment regimen for disseminated prostate cancer; however, its role in patients with localised cancer is less clear. We did a large randomised controlled trial to determine whether 3 months or 6 months of androgen deprivation given before and during radiotherapy improves outcomes for patients with locally advanced prostate cancer. Methods 818 men with locally advanced prostate cancer were randomly assigned to: no androgen deprivation (ie, radiotherapy alone: 66 Gy in 33 fractions of 2 Gy per day over 6·5–7·0 weeks to the prostate and seminal vesicles); 3 months' androgen deprivation with 3·6 mg goserelin given subcutaneously every month and 250 mg flutamide given orally three times a day starting 2 months before radiotherapy (same regimen as control group); or 6 months' androgen deprivation, with the same regimen, starting 5 months before radiotherapy (same regimen as control group). Primary endpoints were time to local failure and prostate-cancer-specific survival; secondary endpoints were distant failure, disease-free survival, and freedom from salvage treatment. Analyses were done by intention to treat. Findings 802 (98%) patients were eligible for analysis. Median follow-up was 5·9 years (range 0·1–8·5). Compared with patients assigned no androgen deprivation, those assigned 3 months' treatment had significantly improved local failure (hazard ratio [HR] 0·56 [95% CI 0·39–0·79], p=0·001), biochemical failure-free survival (0·70 [0·56–0·88], p=0·002), disease-free survival (0·65 [0·52–0·80], p=0·0001), and freedom from salvage treatment (0·73 [0·56–0·96], p=0·025). 6 months' androgen deprivation significantly improved local failure (0·42 [0·28–0·62], p Interpretation 6 months' androgen deprivation given before and during radiotherapy improves the outlook of patients with locally advanced prostate cancer. Further follow-up is needed to estimate precisely the size of survival benefits. Increased radiation doses and additional periods of androgen deprivation might lead to further benefit.