PCWG4 vs PCWG3: Advanced Prostate Cancer Terminology Overhaul

The Prostate Cancer Working Group 4 (PCWG4), published in February 2026, introduces patient-centric updates to advanced prostate cancer trial design, shifting from PCWG3’s clinical state model to a therapeutic indication framework. PCWG4 replaces outdated terms like “castration-resistant prostate cancer” (CRPC), “non-metastatic castration-resistant prostate cancer” (nmCRPC), “metastatic castration-resistant prostate cancer” (mCRPC), “hormone-sensitive prostate cancer” (HSPC), and “castration-sensitive prostate cancer” (CSPC), which PCWG3 used to describe disease based on testosterone levels, with “androgen pathway modulation” (APM) terminology: APM-naïve/sensitive (APMN/S, formerly HSPC/CSPC) for treatment-untreated or early-response states, and APM-resistant (APMR, formerly CRPC) for progression after diverse therapies beyond just castration.

This change, driven by patient feedback on insensitive language and the rise of non-castration APM agents like androgen receptor pathway inhibitors (ARPIs), better reflects modern biology and serial profiling via biopsies. PCWG4 also integrates prostate-specific membrane antigen positron emission tomography (PSMA-PET) for staging and progression (new lesions, not SUV changes), contrasting PCWG3’s reliance on conventional CT/bone scans, while updating bone scan rules: ≥6 new lesions confirm progression without re-scan (vs. PCWG3’s 2-scan confirmation for any new lesions). Overall, these evolve trials toward biomarkers, patient-reported outcomes (PROs, direct patient reports on symptoms, quality of life, and functioning via validated questionnaires), and diversity, optimizing endpoints like radiographic progression-free survival (rPFS) in heterogeneous populations.

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