Treatment interruptions in prostate cancer: Balancing PSA kinetics and quality of life

In this video, Aaron D. Berger, MD, discusses testosterone recovery following treatment interruption with enzalutamide (Xtandi)-based therapy, including findings from the EMBARK trial and the potential effects of testosterone recovery on patients' quality of life. Berger is the Chief Medical Officer and Director of Clinical Research at Associated Urological Specialists in Chicagoland.

Berger reviews testosterone recovery patterns following treatment interruption in the 3-arm phase 3 EMBARK trial, which evaluated enzalutamide monotherapy, androgen deprivation therapy (ADT) alone, and enzalutamide plus ADT.¹ He explains that testosterone recovery can vary depending on the type of ADT used, with patients receiving gonadotropin-releasing hormone (GnRH) antagonists generally experiencing faster recovery than those receiving GnRH agonists. Recovery following antagonist therapy may occur within approximately 90 days, whereas patients receiving injectable agonists may require 6 to 12 months or longer, particularly after prolonged treatment. Berger also discusses how these differences may influence the duration of treatment-free intervals and the timing of prostate-specific antigen (PSA) increases following therapy interruption.

He highlights the potential quality-of-life benefits of testosterone recovery, including improvements in energy, muscle mass, exercise capacity, libido, sexual function, sleep, and cognitive function. However, he emphasizes that these improvements must be considered alongside the possibility of rising PSA levels and disease progression during treatment breaks. Although patients may be reluctant to resume therapy after experiencing improvements in how they feel, Berger notes that decisions about restarting treatment should account for individual disease characteristics rather than relying on a single PSA threshold.

Berger underscores the importance of shared decision-making and regular monitoring when determining how long patients can remain off therapy. He explains that PSA kinetics, particularly PSA doubling time, can help inform discussions about when to resume treatment, with shorter doubling times potentially signaling a greater need for intervention. Ultimately, he emphasizes that treatment decisions should reflect both clinical considerations and patient preferences, particularly for those who prioritize maintaining quality of life during a treatment-free interval. He adds that clinicians should consider each patient's circumstances and respect their preferences when discussing the risks and benefits of remaining off treatment.

Berger notes, “Patients always have the option to say, ‘Can I take a break?’ You just have to explain to them that in different settings, especially in the metastatic setting, it would be considered not necessarily guideline driven to stop therapy at this point.”

REFERENCE

1. Shore ND, Luz MDA, Giorgi UD, et al. Improved survival with enzalutamide in biochemically recurrent prostate cancer. N Engl J Med. 2026;394(6):563-575. doi:10.1056/NEJMoa2510310