What are the implications of 4 months of androgen deprivation therapy (ADT)?

From the Guidelines

At 4 months of androgen deprivation therapy (ADT), patients are at a significant risk of developing osteoporosis, fractures, and other metabolic changes, and should be closely monitored for these adverse effects, with consideration of bisphosphonate therapy or RANK-L monoclonal antibody therapy to mitigate bone loss, as recommended by the most recent guidelines 1. The implications of 4 months of ADT are numerous and can have a significant impact on a patient's quality of life. Some of the key effects of ADT include:

• Osteoporosis and increased risk of fractures, with a 21% to 54% relative increase in fracture risk 1
• Metabolic changes, including insulin resistance, alterations in lipids, and increased risk of diabetes and cardiovascular disease 1
• Decreased libido, erectile dysfunction, hot flashes, depression, and other mood disturbances, fatigue, and weight gain 1 It is essential to note that the side effects of ADT can be mitigated with proper management, including the use of bisphosphonates or RANK-L monoclonal antibody therapy to prevent bone loss, as well as lifestyle modifications to manage metabolic changes and other adverse effects. The most recent guidelines recommend that patients with high-risk features may benefit from extended ADT duration, up to 18 to 24 months, while those with low- or intermediate-risk disease may require shorter durations of ADT, typically 4 to 6 months 1. Overall, the management of ADT requires careful consideration of the potential benefits and risks, as well as close monitoring of patients for adverse effects, to optimize outcomes and minimize morbidity and mortality.

From the Research

Implications of 4 Months of Androgen Deprivation Therapy (ADT)

• The use of 4 months of ADT has been shown to improve overall survival (OS) and disease-specific mortality (DSM) in men with localized prostate cancer when used with radiation therapy 2.
• Short-term ADT may lead to numerous side effects, such as osteoporosis, obesity, sarcopenia, lipid alterations, insulin resistance, and increased risk for diabetes and cardiovascular morbidity 3.
• The administration of 4 months of ADT has been estimated to confer an additional 6 months of life, with OS converging at approximately 15 years 2.
• ADT is associated with an increased risk of multiple side effects that may reduce quality of life and/or OS, and its use should be carefully considered, especially in settings with a high risk-benefit ratio 3, 4.
• The role of ADT in patients with nonmetastatic disease is still evolving, and its use as primary and sole treatment is not recommended, while ADT combined with conventional-dose radiation therapy may delay progression and prolong survival 4.

Side Effects and Risks

• ADT has been associated with various serious adverse events, including cardiovascular disease, diabetes, and skeletal complications that may also affect mortality 4.
• The metabolic effects of ADT on lipids, glycemic control, and bone loss can lead to an increased risk of cardiovascular events and osteoporosis 5.
• The use of ADT should be evidence-based, with special consideration to adverse events and the risk-benefit ratio 4.

Clinical Settings and Treatment Strategies

• ADT is commonly used in various clinical settings, including localized prostate cancer, and its use should be tailored to the individual patient's needs and risk profile 3, 4.
• Intermittent ADT may help mitigate some of the negative effects of ADT in selected patients by allowing for off-treatment intervals 5.
• Newer compounds, such as relugolix, a gonadotropin-releasing hormone (GnRH) antagonist, may offer improved cardiac safety profiles and reduced ADT-related adverse events 6.