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

Using second-generation antiandrogens (AAs) for treating prostate cancer is increasing. Previous research has mentioned an association between second-generation AAs and adverse cognitive and functional outcomes. There is a lack of evidence and data from prospective trials.

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