Short-term androgen deprivation and radiotherapy for locally advanced prostate cancer: Results from the Trans-Tasman Radiation Oncology Group 96.01 randomised controlled trial: Denham JW, Steigler A, Lamb DS, Joseph D, Mameghan H, Turner S, Matthews J, Franklin I, Atkinson C, North J, Poulsen M, Christie D, Spry NA, Tai K-H, Wynne C, Duchesne G, Kovacev O, D’Este C, Trans-Tasman Radiation Oncology

Abstract

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. 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. 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 < 0.0001), biochemical failure-free survival (0.58 [0.46–0.74], p < 0.0001), disease-free survival (0.56 [0.45–0.69], p < 0.0001), freedom from salvage treatment (0.53 [0.40–0.71], p < 0.0001), distant failure (0.67 [0.45–0.99], p = 0.046) and prostate-cancer-specific survival (0.56 [0.32–0.98], p = 0.04) compared with no androgen deprivation. 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.