The Prostate Cancer Working Group 4 guidelines (PCWG4) represent a significant evolution in the framework used to evaluate prostate cancer progression and treatment response in clinical trials. Building on the foundations established by the Prostate Cancer Working Group 3, PCWG4 incorporates advances in imaging technologies, particularly prostate-specific membrane antigen (PSMA) PET, and introduces updated terminology. This review summarizes the updates and additions to PCWG4 guidelines as well as the rationales underpinning these changes. Key developments include replacement of traditional “castration-sensitive” and “castration-resistant” terminology with androgen pathway modulation–based classifications, incorporation of PSMA PET throughout the disease continuum, and further refinement of conventional imaging response criteria. Although conventional imaging modalities such as CT, MRI, and bone scintigraphy remain validated endpoints for regulatory purposes, PSMA PET is increasingly integrated into clinical trial frameworks as noninvestigational for staging and recurrence and as an investigational modality for response assessment. The PCWG4 framework emphasizes standardized visual evaluation, careful classification of new metastatic lesions, and systematic data collection to support future validation of PSMA PET as a clinical trial endpoint. These updates aim to improve the accuracy of disease characterization, facilitate biomarker-driven therapeutic evaluation, and lay the groundwork for further methodologic advancements anticipated in future iterations of the guidelines.
Kuo et al. (Mon,) studied this question.