Systematic Review: Prognostic Molecular Biomarkers in Wilms Tumors

Molecular biomarkers are increasingly used for risk stratification, particularly in up-front surgery settings (Children's Oncology Group trials), whereas in preoperative chemotherapy setting, the ongoing International Society of Pediatric Oncology (SIOP)-Renal Tumor Study Group-2016 UMBRELLA study aims to validate selected biomarkers for future risk-adapted treatment strategies. This systematic review summarizes all literature on the prognostic value of these biomarkers.

A systematic literature review (PubMed and Embase; up to January 2025) included studies with ≥50 de novo Wilms tumors (WTs). Eligible biomarkers included copy number variations; 1q gain, 1p and/or 16q loss of heterozygosity (LOH)/loss, 12 gain, 14q loss, 22 loss, 11p15 LOH/loss of imprinting (LOI), and structural somatic variants (TP53 [and/or 17p loss], MYCN, FBXW7, WT1, WTX, SIX1/SIX2, DROSHA, DGCR8, AMER1, CTNNB1, GPC3, MLLT1, DICER1, DIS3L2). Outcome included relapse-free survival, event-free survival (EFS), and overall survival (OS). Risk of bias was assessed with quality in prognosis studies tool.

Low-bias multivariable/stratified analyses identified 1q gain as worse EFS and 1p and/or 16q LOH/loss as worse EFS/OS prognostic factors, in up-front nephrectomy settings. Preoperative chemotherapy settings revealed similar trends with lacking significance. TP53 and MYCN were adverse prognostic in univariate analyses. No prognostic data were available for the remaining variants.

1q gain and 1p and/or 16q LOH/loss emerge as independent prognostic biomarkers in up-front nephrectomy settings. Evidence remains limited in preoperative chemotherapy settings, particularly when using SIOP-oriented treatment algorithms. Prognostic value of TP53, MYCN, and 11p15 LOH/LOI warrants further validation in both settings. This highlights the need for adequately powered prospective studies, specifically in the preoperative chemotherapy setting, to establish reliable molecular biomarkers.