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.

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 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.

Beyond rigid trial protocols, a flexible approach to first-line T-DXd is practical and patient-centered. This includes discussing treatment breaks for holidays or switching to a less burdensome maintenance regimen (like subcutaneous HP) if a patient is tired of frequent clinic visits, prioritizing their quality of life.

The oral GnRH antagonist Relagolix allows for much quicker testosterone recovery (1-2 months vs. 3-6 for leuprolide). While beneficial in curative-intent settings, this rapid recovery is a double-edged sword that could shorten the "off-therapy" period during intermittent treatment for metastatic disease.

The oral antagonist relugolix allows for rapid testosterone recovery after discontinuation. While useful for planned intermittent therapy, a case study shows this can be a clinical pitfall. In non-adherent patients who self-discontinue, it can lead to an equally rapid rise in PSA and disease progression.

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.

Unlike older studies with ADT monotherapy, the EMBARC and ADREEM trials show that with modern drug combinations and PSMA PET imaging, intermittent therapy is a viable strategy. This allows for safe treatment breaks that improve quality of life by enabling testosterone recovery.

When using intermittent androgen deprivation, GnRH antagonists like relugolix are preferred over LHRH agonists like leuprolide. Antagonists allow for a much faster recovery of testosterone during off-treatment periods, which is a significant quality-of-life benefit for patients. With agonists, testosterone recovery can sometimes take years.