Androgen deprivation therapy for prostate cancer and the risk of bladder cancer: A systematic review of observational studies

Background: Recent interest has been geared towards the potential therapeutic and chemopreventive benefit of androgen deprivation therapy (ADT) for bladder cancer. As a result, several observational studies have investigated this potential association. Given the important side effects associated with ADT treatment, understanding the methodological strengths and weaknesses of the current evidence is warranted. Objectives: The objective of this systematic review was to examine the heterogeneity of the current observational studies on the association between ADT and bladder cancer by assessing the methodological strengths and limitations of these studies. Material and methods: We systematically searched Medline, EMBASE, Healthstar, Cochrane Library Online, Science Citation Index, and Dissertation Abstracts Online, from inception to August 2019 to identify all observational studies investigating the association between ADT and bladder cancer. We assessed overall study quality using the ROBINS-I tool and evaluated the presence of other key pharmacoepidemiologic biases. Results: Overall, our systematic review included 7 observational studies. Five studies reported a decreased risk of bladder cancer with ADT use, 1 study reported no association, and 1 study reported an increased risk. All studies had time-related biases, did not consider a lag period, and had potential residual confounding. Moreover, 1 study had potential detection bias, 6 included prevalent users, 3 had inadequate follow-up durations, 6 had exposure misclassification, and 5 used an inappropriate comparator. Conclusion: Taken together, future methodologically-rigorous studies addressing the limitations underlined in this systematic review are needed to evaluate the important potential association between ADT and bladder cancer. (C) 2020 Elsevier Inc. All rights reserved.