Why phase III trials of maximal androgen blockade versus castration in M1 prostate cancer rarely show statistically significant differences

Abstract

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 meta-analysis all trials where a negative impact of disease flare on survival could not be excluded resulted in no difference in survival between MAB and castration.

Conclusions: Trials of MAB should be planned to detect differences of no more than 5-10% in median survival. The analyses should only be carried out on mature data and should take into account the possibility of a negative impact on survival due to disease flare if no anti-androgen has been given initially with an LH-RH agonist.