# Impact of androgen receptor pathway inhibitors on cognitive function in older adults treated for metastatic prostate cancer

## TL;DR

This study finds that adding ARPI to ADT for prostate cancer in older adults may worsen cognitive function compared to ADT alone.

## Contribution

The study is the first to longitudinally assess cognitive effects of ARPI+ADT in older adults with metastatic prostate cancer.

## Key findings

- Patients on ARPI+ADT showed poorer subjective cognition compared to those on ADT alone.
- Objective cognitive performance in processing speed/attention was lower in ARPI+ADT patients.
- Cognitive impairment was present in over half of ARPI+ADT patients at baseline.

## Abstract

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.

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.

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).

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.

Hormonal treatments for advanced prostate cancer could have an impact on cognition (including memory loss and difficulty concentrating) and affect the daily lives of older adults. This study aimed to assess cognition over a one-year period in patients treated with two different types of hormone therapy. Patients were evaluated using cognitive tests and self-report questionnaires. Results show poorer cognitive function in patients treated with hormone therapy, particularly when new generation androgen receptor pathway inhibitors are added to androgen deprivation hormone therapy. These findings provide a better understanding of the challenges faced by older adults treated for advanced cancer and help identify suitable tools for their evaluation.

Boué et al. longitudinally assess cognition in patients aged ≥70 years receiving hormone therapy for metastatic prostate cancer. Poorer objective and subjective cognition occurs in patients receiving hormone therapy, particularly when androgen receptor pathway inhibitors (ARPI) are added to androgen deprivation therapy (ADT).