Thromboembolic Events Associated with ADT Treatment in Prostate Cancer Patients

Androgen deprivation therapy (ADT) is the mainstay of systemic therapy for men with metastatic or recurrent hormone-sensitive prostate cancer (mHSPC), as well as localized and PSA recurrent prostate cancer when radiation is indicated for higher risk disease. ADT is also continued indefinitely in men with mCRPC, and thus many men with aggressive forms of prostate cancer will be treated with years of ADT and face the cumulative risks of low testosterone.  These risks range from muscle and bone loss, metabolic syndrome and diabetes, cardiovascular risks, hot flashing, and fatigue to name a few, but Guo et al. have now brought attention to a new added risk: blood clots.

Thrombosis (DVTs) and pulmonary embolisms are a leading cause of cancer-related morbidity and mortality, and are particularly high in patients with pancreatic and other GI cancers, lung cancers, and bladder cancers, particularly in the peri-operative setting.  Guo et al examined through a formal meta-analysis the evidence from 5 retrospective population-based studies that met their rigorous inclusion criteria.  They found that GnRH agonists were associated with a higher risk of DVT (HR 1.47 95% CI 1.07-2.03 p=0.017), particularly among African-American men with prostate cancer (HR for AA vs CA men 1.27 95% CI 1.18-1.36 p<0.001). Orchiectomy also resulted in a higher DVT risk (HR 1.8), and ADT plus an anti-androgen increased DVT risk even further (HR 2.55 95% CI 2.21-2.94).  Similarly, elevated risks of PE were seen (HR 2.12-2.26). 

These thrombosis risks remained high despite a range of adjustments for race, geography, Gleason sum, age, and comorbidities but each study did so in heterogeneous ways, limiting our ability to prove causality. Overall, these findings support an association between hormonal therapy and the risk of blood clots but do not prove cause and effect. For example, men with more advanced disease are the ones more likely to receive ADT, and more advanced disease may be the reason for the association.  Prospective studies of long term ADT vs observation (i.e ECOG 3886, or RTOG 9202) for example, did not find such elevated risks but were not designed to rigorously collect such information on DVT risk long term.  As we intensify our hormonal therapies for men with mHSPC and high risk localized/recurrent PC with ADT plus abiraterone, enzalutamide, apalutamide, and darolutamide, it will become important to track these potential adverse effects long term in order to better understand and manage these risks. 

Written by: Andrew J. Armstrong, MD, Medical Oncologist, Tenured Professor of Medicine, Surgery, Pharmacology and Cancer Biology and Associate Director of the Duke Cancer Institute‚Äôs Prostate and Urologic Cancer Center, Associate Editor Journal: Prostate Cancer and Prostatic Diseases

Read the PCAN Full-Text Article:  Association of Androgen Deprivation Therapy with Thromboembolic Events in Patients with Prostate Cancer: a Systematic Review and Meta-analysis
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