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.

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 PCWG criteria are not consensus-based practice guidelines but are proposed frameworks for uniform data collection in trials. They are designed to be tested and validated (or disproven) by data, with the ultimate goal of qualifying biomarkers for drug approval.

The rapid advancement of ARPIs wasn't just a scientific breakthrough. It was a rare convergence of FDA interest in new endpoints, a deeper biological understanding of castration resistance, and intense industry and academic collaboration that created a uniquely fertile ground for innovation.

The PCWG4 imaging committee is comprised of at least 50% non-US experts. This reflects the reality that significant expertise in advanced imaging like PSMA PET resides outside the US, particularly in Australia and Germany, making global collaboration crucial for creating relevant standards.

Data from the CAPItello trial showed a significant number of patients with PTEN deficiency experienced radiological progression without a corresponding PSA increase. This challenges the standard reliance on PSA for monitoring in high-risk prostate cancer and suggests a need for more frequent, personalized imaging protocols to detect progression earlier.

Experts believe molecular tests like Decipher and PTEN status are superior to simply counting bone lesions for guiding treatment. While not yet standard practice for all decisions, this represents a significant shift towards using underlying tumor biology to determine therapy, like adding docetaxel.

Clinical trials use arbitrary, time-based definitions (e.g., relapse within 2 years) for endocrine resistance. This isn't a perfect biological classification but a practical necessity to create homogeneous patient groups for testing, which may not fully reflect the diverse patient population in clinical practice.

New imaging criteria declare immediate progression if a patient develops 6 or more new lesions. For 5 or fewer, the old rule requiring a confirmatory scan applies. This change prevents keeping patients on ineffective therapy just to meet trial criteria while preventing premature declarations for minimal changes.