Impact of androgen receptor pathway inhibitors on cognitive function in older adults treated for metastatic prostate cancer
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Background:
Androgen receptor pathway inhibitors (ARPI) are commonly used in addition to androgen deprivation therapy (ADT) for metastatic prostate cancer (mPC). Despite preliminary results suggesting effects of ADT+ARPI on cognition, there is limited data on their impact in older adults. The objective was to assess cognition in mPC patients ≥70 years receiving ADT+ARPI.
Methods:
This observational study (COG-PRO trial, NCT02907372, registered on 26/07/2016) recruited castration-resistant mPC patients (aged ≥70) receiving ADT+ARPI, patients receiving ADT alone, and healthy controls (HC). Cognition was prospectively assessed using 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). Rates of patients with impairment before ARPI initiation and decline after 3, 6 and 12 months were estimated using international recommendations. Adjusted scores were then analyzed with linear models.
Results:
We report that at baseline (before starting ARPI for ADT+ARPI patients), objective cognitive impairment affects 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 show poorer subjective cognition in ADT+ARPI patients than in ADT patients (p ≤ 0.033). ADT+ARPI patients also have lower objective performance in processing speed/attention domain at all visits (p ≤ 0.010).
Conclusions:
Although limited by small sample sizes, our study shows that ARPI + ADT can increase the risk of impacting objective and subjective cognition in older adults with mPC, compared to ADT alone. Clinician should use specific measures of objective and subjective cognition to assess ARPI-induced cognitive changes.
