Risk of Cognitive Effects in Comorbid Patients With Prostate Cancer Treated With Androgen Receptor Inhibitors

Abstract Prostate cancer (PC) is primarily a disease of older men. As the risk of neurocognitive decline increases as people age, cognitive dysfunction is a potential complication in men with PC, imposing detrimental effects on functional independence and quality of life (QoL). Importantly, risk of cognitive decline may increase with exposure to androgen deprivation therapy (ADT) and other hormonal therapies. Particular consideration should be given to patients with castration-resistant PC (CRPC), many of whom require continuous, long-term ADT combined with a second-generation androgen receptor inhibitor (ARI). Non-comparative evidence from interventional trials of ARIs in men with non-metastatic CRPC suggests differential effects on cognitive function and central nervous system-related adverse events (AEs) within this drug class. Drug–drug interactions with concomitant medications for chronic, non-malignant comorbidities differ among ARIs and thus may contribute further to cognitive impairment. Hence, establishing baseline cognitive function is a prerequisite to identifying subsequent clinical decline associated with androgen receptor-targeted therapies. While brief, sensitive screening tools for cancer-related cognitive dysfunction are lacking, mental status can be ascertained from the initial medical history and neurocognitive examination, progressing to more in-depth evaluation when impairment is suspected. On-treatment neurocognitive monitoring should be integrated into regular clinical follow-up to preserve cognitive function and QoL throughout disease management. This review summarizes the multiple factors that may contribute to cognitive decline in men with CRPC, awareness of which will assist clinicians to optimize individual treatment. Practical, clinic-based strategies for managing the risks for and symptoms of cognitive dysfunction are also discussed.