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Abstract Details

A Retrospective Study of Androgen Targeting Therapies and Incidence of Neurodegenerative Outcomes in Male Prostate Cancer Patients: Implications for Clinic to Bench Translation
Aging and Dementia
S15 - Aging and Dementia 1 (5:06 PM-5:18 PM)

Prostate cancer and multiple neurodegenerative diseases (NDD) share an age-associated pattern of onset. Therapy for metastatic prostate cancer targets androgen and the androgen receptor and is known to impact cognitive function.

To determine whether androgen targeting therapy (ATT) exposure is associated with the risk of NDD in men treated for prostate cancer.
A retrospective cohort study of men aged 45 and older with prostate within the US-based Mariner claims dataset between January 1st and 27th, 2021. Patient claims records were surveyed for a diagnosis of NDD starting 1 year post prostate cancer diagnosis for the duration of enrollment in the claims database. A propensity score approach was used to minimize measured and unmeasured selection bias. Disease risk was determined using Kaplan-Meier survival analyses to determine the association between ATT exposure and diagnosis of NDD in the post index date follow-up period.

Of 1,798,648 men with prostate cancer, 209,722 met inclusion criteria. Mean (SD) follow-up was 6.4 (1.8) years. In the propensity score–matched population, exposure to ATT as a composite group was associated with a minimal increase in NDD incidence (relative risk, 1.07; 95%CI, 1.05-1.10; P<.001). However, GnRH agonists alone were associated with significantly increased NDD risk (RR, 1.47; 95%CI, 1.30-1.66; P<.001). Abiraterone exposure in addition to GnRH was associated with a significantly decreased risk (RR, 0.77; 95%CI, 0.68-0.87; P < .001) of composite NDD.

Among patients with metastatic prostate cancer, GnRH agonist exposure was associated with an increased NDD risk. Specifically, Abiraterone reversed the risks of Alzheimer’s disease and Parkinson’s disease conferred by GnRH agonists whereas risk for ALS was reduced by androgen receptor inhibitors. Outcomes of these analyses contribute to addressing controversies in the field and indicate that GnRH agonism may be a predictable instigator of risk for NDD with opportunities for risk mitigation in combination with another ATT.
Gregory Branigan
Dr. Branigan has nothing to disclose.
Georgina Torrandell Haro (University of Arizona) Miss Torrandell Haro has nothing to disclose.
No disclosure on file
Roberta Diaz Brinton (University of Arizona) Roberta Diaz Brinton, PhD has nothing to disclose.