Retrospective cohort study of metabolic dysfunction after initiation of androgen receptor pathway inhibitors in prostate cancer

Metabolic syndrome (MetS) includes obesity, insulin resistance, hypertension, and dyslipidemia. A retrospective cohort study using the Epic Cosmos dataset investigated the occurrence of MetS during the first year following initiation of androgen deprivation therapy (ADT) concurrent with androgen receptor pathway inhibitor (ARPI) among patients with prostate cancer. The cohort included 16 924 men (mean age 73.1 year; SD 9.1). Medical ADT use predominated, and enzalutamide was the most frequently used ARPI. During the first year following iniation of concurrent ADT and ARPI therapy, the cumulative incidence of MetS increased steadily, reaching nearly 40%. Hypertension was the most frequently documented MetS component outcome. Metabolic associations varied by age, with the highest incidence of MetS among patients aged 70 to 79 years (51.7 events per 1000 person-months; 95% CI 50.7-53.9). Heterogeneity in metabolic outcomes by ARPI type was observed in exploratory analyses. The authors conclude that metabolic abnormalities were frequently documented shortly after initiation of concurrent ADT and ARPI therapy for prostate cancer. This suggests that monitoring should extent beyond cancer-specific outcomes.