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.
While regulators are open to using Patient-Reported Outcomes (PROs) for drug approval, the oncology community reflexively prioritizes survival data. This cultural bias sees PROs as "softer" endpoints, hindering the approval of drugs based on how patients feel and function.
The influential "2+2 rule" on bone scans, which accounts for treatment "flare," wasn't an arbitrary threshold. It was proposed as a working hypothesis to be tested and validated through numerous clinical trials. This exemplifies the data-driven, iterative process behind the PCWG criteria.
PCWG4 replaces terms like "castration-resistant" with "Androgen Pathway Modulation (APM) resistant." This change is driven by patient feedback finding the term "castration" insensitive and by the need for language that reflects modern treatments that don't always involve medical or surgical castration.
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.
The introduction of highly sensitive PSMA PET scans means established endpoints like Metastasis-Free Survival (MFS) may no longer be valid. A metastasis detected by PET likely has a different, better prognosis than one found with older imaging, requiring new validation for this key endpoint.
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.
While PCWG4 advocates for using Patient-Reported Outcomes (PROs), it doesn't mandate specific analysis methods. This flexibility creates a risk where researchers can explore numerous permutations of the data post-hoc to find a result that supports their desired conclusion, whether positive or negative.