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.

A meta-analysis of six trials (Poseidon) found no overall survival benefit from adding long-course (24 months) hormone therapy to post-operative radiotherapy. It suggests that a shorter course of 4-6 months is adequate for most men, marking a significant shift towards treatment de-escalation to reduce long-term toxicity without compromising efficacy in this specific setting.

The confirmatory Code Break 200 study for sotorasib demonstrated a statistically significant improvement in progression-free survival (PFS) over docetaxel. However, it failed to show a similar benefit in overall survival (OS), a critical distinction for oncologists weighing long-term patient outcomes.

The PSMA Addition study, adding lutetium in metastatic hormone-sensitive prostate cancer, showed an RPFS benefit. However, initial data suggested adverse quality of life scores. Upcoming results on pain and skeletal events are critical to determine if the toxicity profile undermines its clinical utility in this earlier disease setting.

Traditional endpoints like progression-free survival (PFS) incentivize continuous treatment. The NCI group proposes "treatment-free survival," a novel metric that quantifies time spent *off* therapy. This endpoint better captures the patient experience and rewards treatments that provide durable responses after a finite course.

For patients with oligometastatic disease who achieve a deep PSA response (e.g., to zero), oncologists consider finite treatment durations (e.g., 18-24 months) followed by observation. This "do less harm" approach challenges the standard of continuous therapy until progression, aiming for long-term treatment-free intervals.

The EMBARK trial demonstrated an overall survival (OS) benefit, yet experts argue this doesn't automatically make treatment mandatory. For asymptomatic patients with a long life expectancy, factors like treatment-free survival and quality of life are critical considerations, challenging the primacy of OS as the sole decision-driver in this population.

In metastatic hormone-sensitive prostate cancer (mHSPC), radiographic progression-free survival (rPFS) is no longer seen as a convincing primary endpoint on its own. Clinicians demand a clear signal for overall survival (OS) improvement, citing historical data where early treatment intensification showed significant OS gains.

The LEAP-010 trial showed a combination therapy improved tumor response and progression-free survival but failed to improve overall survival, the ultimate measure of benefit. This highlights the risk of relying on surrogate endpoints, which can be misleading, especially when a treatment adds significant toxicity.