Androgen deprivation therapy for prostate cancer, measures of adiposity and strength, and adverse cardiovascular outcomes: observations from 3000 men in 5 countries in the RADICAL PC study
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AbstractBackgroundAndrogen deprivation therapy (ADT) is prescribed to nearly half of patients with prostate cancer (PC). ADT is associated with weight gain, reduced muscle strength and increased cardiovascular (CV) risk. However, no PC study has examined the relationship between these physical characteristics, their change with ADT and cardiovascular outcomes.PurposeIn men with PC:To compare 1-year changes in physical measures in those receiving versus not receiving ADTTo evaluate the relationship between physical measures and adverse CV outcomesMethodsWe prospectively studied 3080 men with PC from 37 sites in 5 countries (mean age 68 years), 41% on ADT. Inclusion criteria were one of: PC diagnosed in the past 12 months; started ADT within the past 6 months; or plan to start ADT in the next month. Weight, waist and hip circumference, handgrip strength and get-up-and-go time were recorded at baseline and 1 year. Change in measurements were adjusted for age, education, race, tobacco and alcohol use, baseline cardiovascular disease and renal function. Participants were followed for a median 3 years from enrolment to document adverse CV outcomes associated with adiposity: myocardial infarction, angina, stroke, cerebrovascular disease, peripheral arterial disease, arterial revascularization, heart failure, venous thromboembolism and atrial fibrillation. The relationship between baseline physical measures and outcomes was evaluated by Cox proportional hazards models adjusted for age, diabetes, hypertension, total cholesterol, tobacco use and physical activity levels.ResultsChanges in physical measures are displayed in Table. ADT recipients gained 5x more weight than non-recipients. Weight gain was distributed evenly between waist and hips, resulting in no difference in waist:hip ratio. Muscle strength decreased in both groups but with 43% larger decrease among ADT recipients. The ratio of strength to body weight fell twice as much in ADT recipients as non-recipients. Gait speed slowed by 13% after 12 months’ ADT.We observed 144 adverse CV events. There was a continuous relationship between handgrip strength and CV events. Each quartile reduction in strength was associated with adjusted hazard ratio (95% CI) 1.24 (1.01-1.52). There was no detectable association between other physical measures and CV events.ConclusionADT use is associated with increased adiposity and reduced muscle strength. Low muscle strength, reflected by low handgrip strength is a better predictor of adverse CV outcomes than increased adiposity. These findings may explain help the association between ADT use and adverse CV outcomes.Table
