Second-generation antiandrogens may increase cognitive decline, fatigue and falls in patients with prostate cancer

In this study, researchers determined if evidence from randomized clinical trials (RCTs) in prostate cancer supports an association between second-generation AAs and cognitive or functional toxic effects.

For this, researchers collected data from PubMed, EMBASE, and Scopus. They included RCTs of second-generation AAs (abiraterone, apalutamide, darolutamide, or enzalutamide) among prostate cancer patients that evaluated cognitive toxic effects, asthenic toxic effects (e.g., fatigue, weakness), or falls.

The study results are as follows:

• There were 12 studies comprising 13 524 participants.
• These studies had a low risk of bias.
• Those taking second-generation AAs had an increased risk of cognitive toxic effects and fatigue compared to those in the control arms.
• Increased age was tied to a greater risk of fatigue with second-generation AAs.
• Using second-generation AAs had an increased risk of falls.

Concluding further, based on this systematic review and meta-analysis findings, second-generation AAs carry an increased risk of cognitive and functional toxic effects, including when added to traditional forms of hormone therapy.

Based on the study’s findings, there is a need to prevent, identify, and intervene in cognitive and functional toxic effects in prostate cancer patients receiving second-generation AAs.

Further reading:

Nowakowska MK, Ortega RM, Wehner MR, Nead KT. Association of Second-generation Antiandrogens With Cognitive and Functional Toxic Effects in Randomized Clinical Trials: A Systematic Review and Meta-analysis. JAMA Oncol. Published online May 25, 2023. doi:10.1001/jamaoncol.2023.0998