Two recent studies highlight potential risks associated with androgen deprivation therapy (ADT) for prostate cancer (PCa) that clinicians should discuss with their patients and monitor.
In the British Journal of Cancer, Reina Haque, PhD, MPH, of Kaiser Permanente Southern California, and colleagues reported an 81% higher risk of heart failure in men with localized PCa treated with ADT who initially had no cardiovascular disease (CVD). They also found 44% greater risks of arrhythmia and triple the risk of conduction disorder among ADT recipients with pre-existing CVD. No significant associations were observed for cardiac ischemia, stroke, or other heart diseases.
“The implication is that patients with localized prostate cancer should be followed to minimize the health effects of androgen deprivation therapy on the cardiovascular system,” Dr Haque stated in a press release. “Patients should consider lifestyle changes, and physicians should actively monitor the patient’s health for early signs of heart disease.”
The prospective study included 7637 men (33% younger than 65 years) from the Kaiser Permanente Southern California health system diagnosed with localized PCa during 1998–2008 and followed until 2010. All patients initially were under active surveillance, and 30% eventually received ADT as primary or salvage therapy. The team adjusted Cox proportional hazard models for CVD risk factors and CVD medications, including antiarrhythmics, anticoagulants, antihypertensives, calcium channel blockers, digoxin, nitrates, and antidiabetics. They also accounted for age, ethnicity, tumor characteristics, and recurrence risk.
In a separate systematic review and meta-analysis of 18 studies involving 168,756 individuals with PCa, Kevin T. Nead, MD, MPhil, and colleagues found a significant 41% increased risk of depression among ADT recipients, according to an online report in Urologic Oncology. When only men with localized PCa were considered, that risk rose to 85%, indicating that advanced cancer was not to blame. The study found no differences in risk between men receiving intermittent versus continuous ADT.
Depression was variably identified across studies by billing codes or inventories. However, the relationship between ADT and depression held in analyses of just clinically diagnosed depression.
Depression is a significant predictor of mortality in patients with prostate cancer, Dr Nead and the team noted: “Health care providers should be alert for and have a low threshold to intervene on depressive symptomology among patients with prostate cancer. The risk of depression secondary to ADT use should be discussed with patients and caretakers before initiating treatment.”
Investigators from both studies urged future research to assess the possible effects of ADT type and duration.
Haque R, UlcickasYood M, Xu X, et al. Cardiovascular disease risk and androgen deprivation therapy in patients with localized prostate cancer: a prospective cohort study. Brit J Cancer 2017;1–8. doi: 10.1038/bjc.2017.280
Androgen Deprivation Therapy Associated With Higher Risk of Heart Failure in Men With Early-Stage Prostate Cancer. Kaiser Permanente. Aug 24, 2017 [news release]
Nead KT, Sinha S, Yang DD, and Nguyen PL. Association of androgen deprivation therapy and depression in the treatment of prostate cancer: A systematic review and meta-analysis. Urol Oncol. doi: 10.1016/j.urolonc.2017.07.016