Racial differences in adverse events after androgen deprivation in Veterans with prostate cancer

Abstract: Importance: Androgen deprivation therapy (ADT) for prostate cancer (PC) has been linked to adverse events, such as cardiac events and osteoporosis. Whether these associations differ by race is unknown. Objective: To assess the association between ADT and time to cardiovascular and bone-related adverse events across racial groups. Design, Setting, and Participants: This retrospective, nationwide, population-based, cohort study used electronic health records from the Veterans Affairs Health Care System (VAHCS) database from January 2001 to December 2021, with follow-up until death or study end. Participants included veterans with PC. Patients undergoing bilateral orchiectomy, receiving gonadotropin-releasing hormone antagonists, or lacking data on race and ethnicity were excluded. Data analysis was performed from January to March 2023. Exposure: Luteinizing hormone–releasing hormone agonists (leuprolide, goserelin, or triptorelin) use as a time-dependent variable and first-line systemic therapy. Main Outcomes and Measures: The primary outcome was time to first cardiovascular event (myocardial infarction, stroke, coronary heart disease, congestive heart failure, or peripheral vascular disease). Secondary outcomes included osteoporosis, bone fracture, and a composite event (any of these). Cox models assessed the association between ADT as a time-dependent covariate and time-to-event across all patients by race. Results: Among 790916 veterans with PC (30139 [4%] Hispanic; 145267 non-Hispanic Black [18%]; 598574 non-Hispanic White [76%]; and , 16936 other races [2%]), ADT was associated with increased risk of cardiovascular events (hazard ratio [HR], 1.16; 95% CI, 1.15-1.17; P<.001), bone fractures (HR, 1.59; 95% CI, 1.55-1.62; P<.001), osteoporosis (HR, 2.73; 95% CI, 2.65-2.80; P<.001), and composite event (HR, 1.29; 95% CI, 1.27-1.30; P<.001). When stratified by race, ADT remained significantly associated with all outcomes among all races. Among Black patients, compared with White patients, the excess risk due to ADT was slightly lower for cardiovascular events (HR, 1.09 [95% CI, 1.06-1.17] vs 1.18 [95% CI, 1.16-1.19]) and bone fracture (HR, 1.35 [95% CI, 1.28-1.42] vs 1.65 [95% CI, 1.61-1.70]) but higher for osteoporosis (HR, 3.16 [95% CI, 2.95-3.38] vs 2.64 [95% CI, 2.56-2.73]). HRs for Hispanic patients and those of other races were very similar to those for White patients. Conclusions and Relevance: In this cohort study of 790916 veterans with PC, ADT was associated with increased cardiovascular and bone risks across all racial groups. Although excess risks differed slightly between Black and White patients, overall differences were small. These findings highlight the need for monitoring and mitigation strategies for patients receiving ADT.

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