Reduced Cardiorespiratory Fitness and Increased Cardiovascular Mortality After Prolonged Androgen Deprivation Therapy for Prostate Cancer

Figures

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  Figure 1. Consort Diagram Consort diagram outlining steps used to identify the final study cohort. Patients were excluded if prostate cancer diagnosis occurred after exercise treadmill test (ETT), if data on prostate cancer treatment/vital status were missing, or if exposure to androgen deprivation therapy (ADT) occurred only after ETT.

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  Figure 2. Frequency of Reduced CRF in ADT-Exposed Versus ADT-Naive Patients With PC Frequency of reduced cardiorespiratory fitness (CRF), defined as failure to achieve >8 metabolic equivalents during exercise treadmill testing, was compared in androgen deprivation therapy (ADT)-exposed versus ADT-naive patients with prostate cancer (PC) using chi-square test. Reduced CRF was more frequent among patients with ADT exposure than among those with no ADT exposure (48.7% vs. 32.6%, p < 0.001).

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  Figure 3. Cumulative Incidence of CV Mortality by ADT Exposure Status Cumulative incidence for cardiovascular (CV) mortality for patients with prostate cancer and no androgen deprivation therapy (ADT) exposure (green), ADT exposure of ≤6 months (blue), and ADT exposure of >6 months (red) were compared using Gray test of equality. Incidence was similar for patients with no ADT exposure and those with ≤6 months’ exposure (p = 0.077). Incidence was significantly higher among patients with >6 months’ exposure compared with among ADT-naive patients with prostate cancer (p = 0.029).

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  Central Illustration. Potential Mechanisms Underlying Association of Prolonged ADT Exposure With Reduced CRF and Increased CV Mortality Association of prolonged androgen deprivation therapy (ADT) exposure with reduced cardiorespiratory fitness (CRF) and increased cardiovascular (CV) mortality are presented together with some proposed mechanisms. Baseline CV risk modifies these associations. Reduced CRF may also in part mediate increased risk of CV mortality. ADT exposure may not only directly influence CRF and CV mortality but may also modify the association between CRF and CV mortality. An exercise intervention concurrent with ADT may mitigate against reduced CRF, and whether this could offset some of the increased risk of CV mortality warrants investigation.