Impact of androgen receptor pathway inhibitors on cognitive function in elderly patients treated for metastatic prostate cancer

Androgen receptor pathway inhibitors (ARPI) are commonly used in addition to androgen deprivation therapy (ADT) for metastatic prostate cancer (mPC). However, there is limited data on their cognitive impact in elderly patients. This prospective multicenter trial recruited castration-resistant mPC patients aged ≥70 receiving ADT+ARPI, patients receiving ADT alone, and healthy controls (HC). Cognition was assessed with a self-report questionnaire (subjective cognition) and cognitive tests addressing six domains: processing speed/attention, working memory, verbal memory, visual memory, visuospatial abilities, and executive functions (objective cognition). At baseline (before starting ARPI for ADT+ARPI patients), objective cognitive impairment concerned 36 (51%), 5 (26%) and 3 (10%) ADT+ARPI patients, ADT patients and HC, respectively. After 3 and 6 months of follow-up, adjusted scores showed poorer subjective cognition in ADT+ARPI patients than in ADT patients (p≤0.033). ADT+ARPI patients also had lower objective performance in processing speed/attention domain at all visits (p≤0.010). Although limited by small sample sizes, our study shows for the first time that ARPI+ADT can increase the risk of impacting objective and subjective cognition in elderly mPC patients, compared to ADT alone.