On the basis of the results of previous national and international trials and studies, the Renal Tumour Study Group of the International Society of Paediatric Oncology (SIOP–RTSG) has developed a new study protocol for paediatric renal tumours: the UMBRELLA SIOP–RTSG 2016 protocol (the UMBRELLA protocol). Currently, the overall outcomes of patients with Wilms tumour are excellent, but subgroups with poor prognosis and increased relapse rates still exist. The identification of these subgroups is of utmost importance to improve treatment stratification, which might lead to reduction of the direct and late effects of chemotherapy. The UMBRELLA protocol aims to validate new prognostic factors, such as blastemal tumour volume and molecular markers, to further improve outcome. To achieve this aim, large, international, high-quality databases are needed, which dictate optimization and international harmonization of specimen handling and comprehensive sampling of biological material, refine definitions and improve logistics for expert review. To promote broad implementation of the UMBRELLA protocol, the updated SIOP–RTSG pathology and molecular biology protocol for Wilms tumours has been outlined, which is a consensus from the SIOP–RTSG pathology panel.

Renal tumors comprise approximately 7% of all malignant pediatric tumors. This is a highly heterogeneous group of tumors, each with its own therapeutic management, outcome, and association with germline predispositions. Histopathology is the key in establishing the correct diagnosis, and therefore pathologists with expertise in pediatric oncology are needed for dealing with these rare tumors. While each tumor shows different histologic features, they do have considerable overlap in cell type and histologic pattern, making the diagnosis difficult to establish, if based on routine histology alone. To this end, ancillary techniques, such as immunohistochemistry and molecular analysis, can be of great importance for the correct diagnosis, resulting in appropriate treatment. To use ancillary techniques cost-effectively, we propose a pattern-based approach and provide recommendations to aid in deciding which panel of antibodies, supplemented by molecular characterization of a subset of genes, are required.

In the SIOP Wilms' tumor (WT) studies, preoperative chemotherapy is used as primary treatment, and tumors are classified thereafter by pathologists. Completely necrotic WTs (CN‐WTs) are classified as low‐risk tumors. The aim of the study was to evaluate whether a subset of regressive type WTs (RT‐WTs) (67%‐99% chemotherapy‐induced changes [CIC]) showing an exceptionally good response to preoperative chemotherapy had comparably excellent survivals as CN‐WTs, and to establish a cut‐off point of CIC that could define this subset. The study included 2117 patients with unilateral, nonanaplastic WTs from the UK‐CCLG and GPOH‐WT studies (2001‐2020) treated according to the SIOP‐WT‐2001 protocol. There were 126 patients with CN‐WTs and 773 with RT‐WTs, stages I‐IV. RT‐WTs were subdivided into subtotally necrotic WTs (>95% CIC) (STN‐WT96‐99) (124 patients) and the remaining of RT‐WT (RR‐WT67‐95) (649 patients). The 5‐year event‐free survival (EFS) and overall survival (OS) for CN‐WTs were 95.3% (±2.1% SE) and 97.3% (±1.5% SE), and for RT‐WTs 85.7% (±1.14% SE, P < .01) and 95.2% (±0.01% SE, P = .59), respectively. CN‐WT and STN‐WT96‐99 groups showed significantly better EFS than RR‐WT67‐95 (P = .003 and P = .02, respectively), which remained significantly superior when adjusted for age, local stage and metastasis at diagnosis, in multivariate analysis, whereas OS were superimposable (97.3 ± 1.5% SE for CN‐WT; 97.8 ± 1.5% SE for STN‐WT96‐99; 94.7 ± 1.0% SE for RR‐WT67‐95). Patients with STN‐WT96‐99 share the same excellent EFS and OS as patients with CN‐WTs, and although this was achieved by more treatment for patients with STN‐WT96‐99 than for patients with CN‐WT, reduction in postoperative treatment of these patients may be justified.