Why phase III trials of maximal androgen blockade versus castration in M-1prostate cancer rarely show statistically significant differences

BACKGROUND. The meta-analysis of maximal androgen blockade (MAB) concluded that there is no survival advantage of MAB over castration alone. However, the results from the largest trials yield conflicting results. METHODS. The design and results of three trials were examined. RESULTS. Most studies were planned to detect an over-optimistic difference in survival and immature data were published. The survival curves show that statistical assumptions are not fulfilled. Excluding from the mete-analysi s all trials where a negative impact of disease flare on survival could not be excluded resulted in no difference in survival between MAB and castrati on. CONCLUSIONS. Trials of MAB should be planned to detect differences of no mo re than 5-10% in median survival. The analyses should only be carried out o n mature data and should take into account the possibility of a negative im pact on survival due to disease flare if no anti-androgen has been given in itially with an LH-RH agonist. Prostate 48:29-39, 2001. (C) 2001 Wiley-Liss , Inc.