Metabolic Syndrome Emerges Rapidly in First Year of ADT-ARPI Therapy for Prostate Cancer
核心洞察
A retrospective cohort study of 16,924 men found nearly 40% developed newly documented metabolic syndrome (搜索) within 12 months of starting concurrent ADT and ARPI therapy.
Hypertension (搜索) was the most frequently documented abnormality, with a 12-month cumulative incidence of 83.0%, followed by dyslipidemia (搜索) (51.8%), obesity (搜索) (40.5%), and insulin resistance (搜索) (24.0%).
Metabolic abnormalities appeared early, with a median time to first detection of 1.0 month and median time to metabolic syndrome (搜索) of 2.6 months.
Nearly 40% of men with prostate cancer (搜索) developed newly documented metabolic syndrome (搜索) within the first year of beginning concurrent androgen deprivation therapy (ADT) and an androgen receptor (搜索) pathway inhibitor (ARPI), according to a large retrospective cohort study published in JAMA Oncology. The findings, led by Amy L. Shaver, PhD, PharmD, MPH, and colleagues, underscore the need for early metabolic monitoring during treatment.
Metabolic syndrome (搜索) encompasses a cluster of abnormalities including obesity (搜索), insulin resistance (搜索), hypertension (搜索), and dyslipidemia (搜索). While ADT is already known to increase metabolic risk, less has been understood about the timing and burden of metabolic dysfunction among patients receiving ADT together with newer ARPIs, which are increasingly used earlier in the course of prostate cancer (搜索) treatment.
Study Design and Patient Population
The investigators conducted a retrospective cohort study using Epic Cosmos, a large deidentified electronic health record database. The analysis included adult men treated at U.S. institutions who had prostate cancer (搜索) and received concurrent ADT and an ARPI between January 2014 and September 2025. ARPIs included abiraterone acetate, apalutamide, darolutamide, and enzalutamide.
Patients with documented metabolic syndrome (搜索), hypertension (搜索), obesity (搜索), insulin resistance (搜索), or dyslipidemia (搜索) during the six months before treatment initiation were excluded. Because the study relied on electronic health records, the investigators cautioned that some chronic metabolic conditions may have been present but undocumented before treatment. For that reason, study outcomes represent newly documented metabolic abnormalities rather than definitively new-onset disease.
The cohort included 16,924 men with a mean age of 73.1 years. Thirty-five percent were younger than 70 years, 40% were aged 70 to 79 years, and 25% were aged 80 years or older. Medical ADT was used in 96.8% of patients, and enzalutamide was the most commonly used ARPI.
The primary endpoint was the incidence of metabolic syndrome (搜索) during the 12 months after concurrent ADT-ARPI treatment began. Secondary endpoints included hypertension (搜索), obesity (搜索), dyslipidemia (搜索), and insulin resistance (搜索).
Key Findings
The cumulative incidence of metabolic syndrome (搜索) increased steadily during the first year after ADT-ARPI initiation, reaching 39.1% at 12 months. Incidence differed by age, reaching 37.2% among men younger than 70 years, 41.7% among those aged 70 to 79 years, and 37.8% among those aged 80 years or older.
Hypertension (搜索) was the most frequently documented metabolic abnormality, with a 12-month cumulative incidence of 83.0%. The corresponding incidences were 51.8% for dyslipidemia (搜索), 40.5% for obesity (搜索), and 24.0% for insulin resistance (搜索).
Metabolic abnormalities also appeared early in the treatment course. Among patients with a documented metabolic abnormality, the median time to first detection was 1.0 month. Median time to metabolic syndrome (搜索) was 2.6 months, compared with 1.2 months for hypertension (搜索), 2.3 months for dyslipidemia (搜索), and 1.6 months for insulin resistance (搜索).
Age was associated with several metabolic outcomes. Compared with men younger than 70 years, those aged 70 to 79 years were more likely to develop insulin resistance (搜索), hypertension (搜索), dyslipidemia (搜索), and metabolic syndrome (搜索). The investigators also observed differences among individual ARPIs, but emphasized that these comparisons were exploratory and should not be interpreted as evidence for selecting one ARPI over another.
Study Limitations
The study did not include an ADT-only comparison group. The investigators therefore could not determine how much of the observed metabolic burden was attributable specifically to ARPI therapy rather than ADT itself, aging, underlying cardiometabolic risk, or prostate cancer (搜索)-related factors. Increased clinical surveillance after treatment initiation also may have contributed to detection of abnormalities that were already present.
Clinical Implications
The authors said the findings reinforce the importance of monitoring blood pressure, glucose, and lipid levels early during treatment and incorporating cardiometabolic risk management into prostate cancer (搜索) care.
"Metabolic outcomes varied by age and treatment context, underscoring the importance of early and systematic metabolic monitoring," they concluded. "Multidisciplinary strategies that incorporate cardiometabolic risk assessment and mitigation are needed to optimize long-term outcomes for men with prostate cancer (搜索)."
The rapid emergence of metabolic abnormalities supported systematic monitoring for metabolic syndrome (搜索) and its individual components during concurrent ADT and ARPI therapy. The researchers suggested that this could ideally form part of multidisciplinary care, with earlier identification of cardiometabolic risk potentially allowing appropriate interventions. The study also highlighted the need for scalable approaches to managing metabolic health in men receiving prostate cancer (搜索) treatment, with further research needed to evaluate interventions designed to reduce the early cardiometabolic burden associated with these therapies.