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 with biochemically recurrent prostate cancer, the decision to treat hinges on PSA doubling time. A doubling time of over two years carries a low risk of metastasis, often warranting observation. Conversely, a doubling time under three months indicates a high risk of metastasis within three years, necessitating intervention.

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 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.

Some men strongly resist continuous androgen deprivation due to its impact on identity and quality of life. Intermittent therapy, pausing treatment after a good response, offers a compromise, allowing for testosterone recovery and a break from side effects.

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.

For biochemically recurrent prostate cancer, the speed at which PSA doubles is a more powerful predictor of outcomes than the absolute value. A doubling time of less than three to nine months indicates highly aggressive disease requiring more intensive treatment consideration.