After years of treatment intensification, a new focus in metastatic hormone-sensitive prostate cancer is de-escalation. Trials like ADREAM are evaluating planned treatment interruptions for patients with excellent responses, aiming to provide 'treatment-free intervals' that improve quality of life without sacrificing efficacy.

For patients who meet EMBARK criteria but also show oligometastatic disease on PSMA PET, clinicians are adopting a pragmatic approach. They combine the evidence-backed systemic hormone therapy from the trial with targeted radiation of metastatic sites, aiming to prolong the time until therapy needs to be restarted.

The EMBARK trial showed that enzalutamide monotherapy was superior to standard ADT monotherapy for metastasis-free survival. This suggests potent AR antagonism may be a more effective strategy than simply depleting the testosterone ligand, challenging the long-held dogma of ADT being the fundamental building block for systemic prostate cancer therapy.

After years of successfully intensifying hormonal therapy, the focus in prostate cancer is shifting toward de-intensification. Researchers are exploring intermittent therapy for top responders and developing non-hormonal approaches like radioligands to spare patients the chronic, life-altering side effects of permanent castration.

The advent of highly sensitive PSMA PET imaging is changing the management of biochemically recurrent prostate cancer. Rather than relying on fixed PSA thresholds from older trials like EMBARK to restart therapy, clinicians now use PET imaging at lower PSA levels to guide decisions, aiming to extend treatment-free intervals.

The EMBARC study's "intermittent" arm is misleading. It tested only one treatment-free period, limited to extreme responders who achieved an undetectable PSA. Therapy was then resumed continuously until progression, making it more akin to a trial for metastatic hormone-sensitive disease with a single break, not a model for real-world, multi-cycle intermittent therapy.

The EMBARK study demonstrates that an intermittent approach to androgen deprivation therapy (ADT), especially with combination ADT and enzalutamide, can provide patients with low-volume metastatic disease a median of 1.5 years off therapy, improving quality of life without compromising outcomes.

For patients with conventionally negative imaging but positive PSMA PET scans (oligometastatic disease), continuous intensified therapy may be overtreatment. A new paradigm involves metastasis-directed therapy followed by a short course of escalated treatment, then stopping to observe. This "time-limited" approach balances efficacy with reducing long-term treatment burden.

For high-risk biochemically recurrent prostate cancer, intermittent androgen deprivation therapy (ADT) is the standard of care, not continuous therapy. This approach significantly improves quality of life, bone health, and metabolic health while effectively delaying progression to metastatic disease for years. Continuous therapy is vehemently discouraged in this setting.