Maximum androgen blockade in advanced prostate cancer: an overview of the randomised trials

Background In advanced prostate cancer, androgen suppression (AS) by surger y or drugs controls testicular hormone secretion, and the further addition of an antiandrogen such as nitutamide, flutamide, or cyproterone acetate is referred to as maximum androgen blockade (MAB), The aim of this overview w as to compare the effects on the duration of survival of MAB and of AS alon e. Methods The collaborative meta-analysis of 27 randomised trials involved ce ntral reanalysis of the data on each of 8275 men (98% of those ever randomi sed in trials of MAB vs AS) with metastatic (88%) or locally advanced (12%) prostate cancer. Half were over 70 years of age, and follow-up was typical ly for about 5 years. Findings 5932 (72%) men have died; of the deaths for which causes were prov ided, about 80% were attributed to prostate cancer. 5-year survival was 25. 4% with MAB versus 23.6% with AS alone, a non-significant gain of 1.8% (SE 1.3; logrank 2p=0.11). There was no significant heterogeneity in the treatm ent effect (MAB vs AS) with respect to age or disease stage. The results fo r cyproterone acetate, which accounted for only a fifth of the evidence, ap peared slightly unfavourable to MAB (5-year survival 15.4% MAB vs 18.1% AS alone; difference -2.8% [SE 2.4]; logrank 2p=0.04 adverse), whereas those f or nilutamide and flutamide appeared slightly favourable (5-year survival 2 7.6% MAB vs 24.7% AS alone; difference 2.9% [SE 1.3]; logrank 2p=0.005). No n-prostate-cancer deaths (although not clearly significantly affected by tr eatment) accounted for some of the apparently adverse effects of cyproteron e acetate. Interpretation In advanced prostate cancer, addition of an antiandrogen to AS improved the 5-year survival by about 2% or 3% (depending on whether the analysis includes or excludes the cyproterone acetate trials), but the ran ge of uncertainty as to the true size of this benefit runs from about 0% to about 5%.