Preoperative Chemotherapy and Its Efficacy in Pediatric Wilms Tumor: A Systematic Review of Randomized Controlled Trials

Wilms tumor (nephroblastoma) is the most common malignant renal tumor in children. Preoperative (neoadjuvant) chemotherapy has been widely adopted to reduce tumor size, facilitate surgical resection, and decrease the risk of intraoperative tumor rupture. However, the magnitude of its clinical benefits remains a subject of debate. This systematic review aimed to evaluate the effectiveness of preoperative chemotherapy in children with Wilms tumor in terms of tumor shrinkage, complete tumor resection, and event-free survival (EFS). This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Google Scholar, and ScienceDirect were searched for randomized controlled trials (RCTs) published up to 2024 that evaluated preoperative chemotherapy in pediatric patients with Wilms tumor. Eligible studies compared preoperative chemotherapy with upfront surgery, alternative chemotherapy strategies, or different durations of preoperative treatment. Data extraction and risk-of-bias assessment were performed independently by two reviewers. Due to the limited number of studies and substantial clinical heterogeneity, a narrative synthesis was conducted instead of a meta-analysis. Three RCTs involving 631 pediatric patients were included. Preoperative chemotherapy consistently resulted in significant tumor shrinkage and facilitated surgical management. A reduction in intraoperative complications, particularly tumor rupture, was observed in patients receiving preoperative therapy compared with upfront surgery. Survival outcomes were generally comparable between treatment groups, with no significant improvement in EFS or overall survival (OS) associated with prolonged preoperative treatment. Evidence from one trial demonstrated improved tumor response and reduced perioperative blood loss with trans-arterial chemoembolization combined with surgery. Overall, extending preoperative chemotherapy beyond four weeks did not provide additional clinical benefit. These findings suggest that preoperative chemotherapy in pediatric Wilms tumor improves tumor shrinkage and surgical feasibility while reducing operative complications. Current evidence does not support extending treatment duration beyond standard short-course regimens, as longer courses do not appear to improve survival outcomes and may increase treatment-related toxicity. Further high-quality randomized studies are needed to strengthen the evidence base and clarify long-term outcomes.