Prostate Cancer Working Group 4 Publishes Landmark Recommendations in the Journal of Clinical Oncology
Comprehensive Guidance Document Establishes New Standards for Prostate Cancer Clinical Trial Design in Era of Precision Medicine
New York, NY – February 26, 2026 – The Prostate Cancer Clinical Trials Consortium (PCCTC) today announced the publication of the Prostate Cancer Working Group 4 (PCWG4) recommendations in the Journal of Clinical Oncology. The comprehensive manuscript, Trial Design and Objectives for Patients With Prostate Cancer: Recommendations From the Prostate Cancer Working Group 4, provides updated standards for clinical trial design, patient eligibility, and outcome measures in advanced prostate cancer.
Building on the widely adopted PCWG3 framework, PCWG4 reflects the dramatic evolution in clinical trial conduct driven by advances in imaging approaches, molecular phenotyping, genetic subtypes, and effective therapies across multiple disease states. The recommendations were developed by an international, multidisciplinary expert committee that convened between 2016 and 2025 to address today's more heterogeneous and diverse patient population.
Key Updates Include:
Redefined disease state terminology and prior therapy classifications in a patient-centric context, moving away from castration-sensitive/castration-resistant nomenclature
New imaging-specific radiographic progression-free survival (rPFS) criteria, including guidance for serial PSMA PET/CT imaging
Expanded response assessments incorporating pathology, ctDNA, circulating tumor cells, and PSA declines
Recommendations for both androgen pathway modulator-naïve/sensitive and resistant settings
Specified intervals for imaging, biomarker assessments, and patient-reported outcomes
Updated eligibility criteria emphasizing representation and inclusion of diverse patient populations
"PCWG4 represents a critical evolution in how we design and conduct prostate cancer clinical trials in an era of precision medicine," said Dr. Andrew Armstrong of Duke University, co-first author of the recommendations. "These updated recommendations emphasize the need for continued development and validation of PET imaging and molecular criteria to appropriately risk-stratify patients, predict and assess treatment benefit, and measure post-treatment outcomes reliably. Ultimately, these recommendations should accelerate personalized therapeutic development, maximizing survival and quality of life improvements to those patients most likely to benefit."
The PCWG4 prostate cancer clinical state model, a framework for patient treatment and drug development, updated for Prostate Cancer Clinical Trials Working Group 4. Combination therapy is considered one line of therapy. Androgen pathway modulation includes ADT and ARPI. Within each state, specify where relevant: (1) genotype (germline, somatic), (2) imaging modality used to define metastasis (PET, CT/MRI/bone scan), (3) disease characteristics and biomarkers critical for risk stratification, including pathology and immunohistochemistry, and (4) previous therapies and outcome including lack of exposure (treatment-naïve), exposed but not resistant, and resistant. APMN/S is the preferred term for hormone-/castration-naïve/castration-sensitive disease (HSPC, CSPC), whereas APMR is the preferred term for castration-/hormone-resistant prostate cancer (CRPC/HRPC). Mapping of previous PCWG3 disease states to the current PCWG4 state model is shown in Appendix Table A1. ADT, androgen deprivation therapy; APMN/S, androgen pathway modulation–naïve/sensitive; APMR, androgen pathway modulator–resistant; ARPI, androgen receptor pathway inhibitor; CSPC, castration-sensitive prostate cancer; CT, computed tomography; HSPC, hormone-sensitive prostate cancer; MRI, magnetic resonance imaging; PCWG, Prostate Cancer Clinical Trials Working Group; PET, positron emission tomography.
Co-first author Dr. Michael Morris of Memorial Sloan Kettering Cancer Center added, "PCWG4 refines clinical trial eligibility, end points, objectives, and serial biological and patient-centric classifications of advanced prostate cancer, along with updated nomenclature to inform design of clinical trials. The PCWG4 framework not only updates recommendations on patient and tumor characterization, therapy development, and imaging criteria but also extends guidance into earlier androgen pathway modulator-naïve/sensitive disease states to reflect an evolving, heterogeneous, and diverse patient population to optimize treatment benefits for all patients."
The manuscript emphasizes several critical areas for clinical trial optimization:
Patient-reported outcomes as key measures of clinical benefit
Baseline molecular characterization to guide trial selection and biomarker development
Incorporation of PSMA-PET imaging where feasible
Development of validated response biomarkers following FDA BEST criteria
Dose optimization strategies aligned with FDA Project Optimus
About the Prostate Cancer Working Group 4 (PCWG4):
PCWG4 is an international working group of clinical and translational prostate cancer experts dedicated to establishing best practices for clinical trial design and conduct. The group includes leading experts from major cancer centers worldwide who collaborate to advance precision medicine approaches in prostate cancer care.
The full manuscript is now available in the Journal of Clinical Oncology at https://ascopubs.org/doi/pdfdirect/10.1200/JCO-25-02834
