Systematic Review: Prognostic Molecular Biomarkers in Wilms Tumors.

Abstract

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 (<i>TP53</i> [and/or 17p loss], <i>MYCN</i>, <i>FBXW7</i>, <i>WT1</i>, <i>WTX</i>, <i>SIX1/SIX2</i>, <i>DROSHA</i>, <i>DGCR8</i>, <i>AMER1</i>, <i>CTNNB1</i>, <i>GPC3</i>, <i>MLLT1</i>, <i>DICER1</i>, <i>DIS3L2</i>). 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. <i>TP53</i> and <i>MYCN</i> 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 <i>TP53</i>, <i>MYCN</i>, 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.