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.

During the consensus meeting, patient advocates successfully argued for a highly robust definition of "event-free survival." The final definition counts not just cancer recurrence, but also the need for any additional standard-of-care treatment—including intravesical therapy—as an "event," reflecting the patient's perspective on what constitutes a successful outcome.

With pirtobrutinib, time to next treatment often exceeds progression-free survival. This discrepancy exists because disease progression is frequently slow and asymptomatic, meaning clinicians do not need to switch therapies immediately upon seeing radiographic changes, allowing for longer treatment duration.

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.

The study utilized "interruption-free survival" as a primary endpoint, a pragmatic measure derived from real-world data. This serves as a valuable surrogate for treatment toxicity, as clinicians typically pause treatment in response to adverse events, providing a quantifiable measure of a drug's real-world tolerability.

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.

Immunotherapies can be effective even without causing significant tumor shrinkage. Immunocore's drug KimTrack had a low 5-7% objective response rate (ORR) but demonstrated a massive overall survival (OS) benefit, challenging the reliance on traditional chemotherapy metrics for evaluating modern cancer treatments.

The term "functional cure" is misleading and hinders progress. With one-third of heavily pretreated patients in the Cartitude 1 trial remaining disease-free for five years without maintenance, the data supports the classical definition of a "cure" used in other cancers. This semantic shift is crucial for advancing the field.