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

Abstract

Prostate cancer (PC) is pr imar ily 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. Importantly, risk of cognitive decline may increase with exposure to androgen deprivation therapy and other hormonal therapies. Particular consideration should be given to patients with castrationresistant PC (CRPC), many of whom require continuous, long-term androgen deprivation therapy combined with a second-generation androgen receptor inhibitor. Non-comparative evidence from interventional trials of androgen receptor inhibitors in men with non-metastatic CRPC suggests differential effects on cognitive function and central nervous system-related adverse events within this dr ug class. Dr ug-dr ug 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. Although 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 quality of life 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.

Risk of cognitive impairment in men with advanced prostate cancer treated with NHAs: A systematic review and network meta‐analysis

“…Previous studies failed to perform meta-analysis because cognition function change was not viewed as a frequent adverse event, and published articles usually lack useful and important relevant data. 54,55 We found these data in the EMA, the FDA, and clini cal.gov safety reports. Besides, we used network meta-analysis to compare four NHA simultaneously.…”

“…To our knowledge, this is the first study to compare four NHA side effects in cognitive function by using meta‐analysis. Previous studies failed to perform meta‐analysis because cognition function change was not viewed as a frequent adverse event, and published articles usually lack useful and important relevant data 54,55 . We found these data in the EMA, the FDA, and http://clinical.gov safety reports.…”

Androgen receptor pathway inhibitors, prostate cancer, and older adults: a global Young International Society of Geriatric Oncology drug review

“…Cognitive decline occurs with advancing age and may be worsened by exposure to ADT and treatment with enzalutamide. 58 Cognitive dysfunction markedly affects patients’ QoL, 59 reduces decision-making capacity with autonomy, 60 and may even contribute to cancer-related mortality, 61 making cognition a central component of the GA. A recent review by Morgans et al 58 summarized factors contributing to cognitive decline in patients requiring androgen deprivation for their prostate cancer. Such factors include the following:…”

With New Technology Comes Great Responsibility: Prostate-Specific Membrane Antigen Imaging in Recurrent Prostate Cancer

“…Obviously, with ADT, time to PSA progression could be improved but perhaps at great cost to quality of life for men who may have 5-10 years until radiographic progression on CT or Tc99 scans, so patient selection will be important. 21-23…”

“…Obviously, with ADT, time to PSA progression could be improved but perhaps at great cost to quality of life for men who may have 5-10 years until radiographic progression on CT or Tc99 scans, so patient selection will be important. [21][22][23] What is missing in this equation is knowledge of the natural history of PSMA PET-positive disease. Although extrapolations from existing mCSPC data are possible, there is great risk in these assumptions.…”