Updated Favorable histology Wilms tumor risk stratification: Rationale for future Children’s Oncology Group clinical trials

Patients with Wilms tumor (WT) have benefitted from decades of large collaborative clinical trials leading to improved care. In the National Wilms Tumor Study Group and now Children’s Oncology Group (COG) trials, risk stratification evolved and expanded with each generation of studies, and as a result, ensuring that each patient receives the appropriate therapy has become increasingly complex. This review describes the evolution of risk-based treatment and outlines the rationale for a new risk stratification system that forms the basis for the upcoming COG favorable histology WT (FHWT) study. Additionally, topics of diagnostic and prognostic uncertainty are highlighted, with explanations of their integration into the central review determination of staging of FHWT by committee consensus to facilitate clinical classification for therapeutic studies. Clear documentation of the elements of current risk stratification are of particular importance as refinement of classification of patients with FHWT continues in effort to optimize research, personalize treatment, and provide an educational resource.