Lage, Daniel E.

PURPOSE The continuous development of new imaging approaches, molecular phenotyping, genetic subtypes, prognosis assessments, and effective therapies across a range of disease states has created a need to redefine terminology and best practices for clinical trial conduct in patients with advanced prostate cancer. Methods We convened an international expert committee of diverse working groups, the Prostate Cancer Working Group 4 (PCWG4), between 2016 and 2025. Our objective was to formulate updated criteria based on emerging evidence and clinical trial data in a biomarker context to provide guidance for clinical trial design, eligibility, and end point assessments for patients with advanced prostate cancer. RESULTS PCWG4 redefines terminology around the disease state and previous therapies in a patient-centric context and terminology focused on androgen pathway modulation. We consider imaging, with a particular focus on positron emission tomography (PET)–defined disease. New recommendations are provided for disease state terminology, defining eligibility criteria, response and delay/prevent end points, intervals for reassessments including imaging, and patient-reported outcome determination. We provide recommendations in a biomarker-based context of use for the intended indication, reflective of patient benefit for specific interventions. We emphasize the need for development of validated PET imaging and molecular and phenotypic criteria as well as trial designs to appropriately risk stratify patients, predict and assess benefit, and measure post-treatment outcomes reliably in a trial framework. CONCLUSION PCWG4 updates recommendations on patient and tumor characterization, therapy development, and imaging criteria and 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 burden of cancer and oncologic treatment is reflected not only through morbidity and mortality, but also through impacts on patient quality of life (QoL). However, QoL has not been historically measured or addressed with the same rigorous methodology as traditional disease-related outcomes such as overall survival and progression, as these are driven by objective measurements and events. Prostate cancer (PCa) is one of the most prevalent non-cutaneous cancers in men around the world. Both the cancer and its treatment significantly impact patients’ physical, emotional, sexual, social, and overall QoL. Ensuring assessment and integration of QoL in research and clinical care enables improvement in treatment outcomes that matter most to patients while also facilitating alignment of healthcare priorities with reimbursements. Great strides toward this end have been made over the last decade, but significant room for improvement remains. To ensure high quality, reliable data collection, QoL assessment tools must be psychometrically validated, standardized, widely implemented across trials, and regularly assessed to allow internal and external validity, longitudinal comparative effectiveness research, and quality control. Additional consideration should be taken for instruments used to measure the aspects of QoL specific to minority, caregiver, and elderly populations. Open clinical questions include how providers should weight changes in different QoL subscales and how clinically meaningful difference thresholds should be defined. Review of ongoing clinical trials encouragingly reveals an increased focus on measuring and improving QoL for men with PCa which will inform the way we utilize QoL assessments. However, additional efforts herein described are needed to fully optimize these processes. In summary, this review will explain the rationale for QoL assessments in PCa populations, discuss requirements for effective implementation, describe considerations for vulnerable and under-evaluated populations, and summarize ongoing clinical trials assessing patient QoL.