Metabolic Dysfunction After Initiation of Androgen Receptor Pathway Inhibitors in Prostate Cancer

Area of Science:

• Oncology
• Endocrinology
• Cardiology

Background:

• Metabolic syndrome (MetS) comprises obesity, insulin resistance, hypertension, and dyslipidemia.
• Androgen deprivation therapy (ADT) is linked to increased risks of dyslipidemia, adiposity, and MetS.
• Limited data exist on MetS occurrence and timing with concurrent ADT and androgen receptor pathway inhibitor (ARPI) therapy, especially concerning age variations.

Purpose of the Study:

• To characterize MetS occurrence and rate within the first year of initiating concurrent ADT-ARPI therapy.
• To examine associations between MetS and patient age and ARPI type.
• To evaluate individual metabolic component outcomes.

Main Methods:

• Retrospective cohort study using deidentified health records (Epic Cosmos) from January 2014 to September 2025.
• Included prostate cancer patients initiating ADT-ARPI (abiraterone acetate, enzalutamide, apalutamide, darolutamide) without prior MetS.
• Follow-up of up to 12 months post-treatment initiation; data analyzed October 2025-January 2026.

Main Results:

• The cohort comprised 16,924 men (mean age 73.1 years); enzalutamide was the most common ARPI.
• Cumulative incidence of MetS reached nearly 40% within the first year, varying by age group.
• Hypertension was the most frequent component; highest MetS incidence observed in patients aged 70-79 years.

Conclusions:

• Metabolic abnormalities are frequently observed shortly after initiating concurrent ADT and ARPI therapy for advanced prostate cancer.
• Monitoring should encompass early detection of metabolic dysfunction, ideally via multidisciplinary care.
• The significant early burden of metabolic abnormalities necessitates evaluation of interventions for cardiometabolic risk in this population.