The NCI working group concluded that neither metastasis-directed therapy (MDT) nor systemic hormonal therapy should be required as a control arm in trials for biochemically recurrent (BCR) prostate cancer. This facilitates testing novel non-hormonal agents and reflects that surveillance is often a reasonable standard of care.

For an older patient population, the ultimate goal in prostate cancer treatment might not be a traditional cure, but rather turning it into a quiescent, chronic disease manageable with well-tolerated therapy, similar to HIV. This reframes success as long-term control until a patient dies of other causes.

Medical progress isn't just about new therapies; it's also about de-escalation, such as reducing the number of radiotherapy sessions. This type of innovation significantly improves a patient's quality of life by minimizing the exhaustive and disruptive time spent in treatment, a benefit patients value highly.

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.

Traditional non-inferiority trials for reducing treatment are difficult to fund and execute. A proposed paradigm shift is to use superiority trial designs, where the burden of proof is on demonstrating that a higher dose or longer duration of therapy is actually better than a de-escalated approach.

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 next frontier in CSCC isn't just about new drugs, but about optimizing existing ones. A key research area is determining the minimum number of immunotherapy doses required for an optimal response—potentially just one or two—to limit toxicity, reduce treatment burden, and personalize care for high-risk patients.

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.