Neuroblastoma, the most common solid tumor outside the brain in children under five, presents a clinical paradox: some tumors regress spontaneously while others resist intensive therapy. A new narrative review, published in the World Journal of Pediatric Surgery on January 6, 2026, synthesizes current evidence to offer a risk-guided approach that tailors treatment to each child's specific disease profile.
Led by specialists from the Royal Hospital for Children in Glasgow and the University of Liverpool, the review integrates diagnosis, risk classification, surgery, chemotherapy, immunotherapy, and survivorship into a single framework. It underscores that outcomes depend not only on tumor stage but also on age, histology, chromosomal changes, and molecular features such as MYCN amplification. This comprehensive perspective is crucial because neuroblastoma accounts for about 15% of pediatric cancer deaths, with five-year survival exceeding 90% for low- and intermediate-risk cases but dropping below 60% for high-risk disease.
The review highlights that pretreatment risk assessment shapes every step of care. Approximately 70% of patients present with abdominal disease, and diagnosis typically combines urine catecholamine testing, MRI, MIBG scintigraphy, bone marrow assessment, biopsy, and genetic profiling. The International Neuroblastoma Risk Group Staging System (INRGSS) uses imaging findings and image-defined risk factors (IDRFs) to classify disease before treatment. Molecular markers add another layer: MYCN amplification, present in roughly one-quarter of tumors and 40-50% of high-risk cases, signals aggressive behavior.
Treatment ranges from observation or surgery alone in selected infants and low-risk patients to intensive multimodal therapy for high-risk disease. For carefully selected infants monitored without immediate intervention, a prospective study reported 10-year event-free survival of 94.7% and overall survival of 97.4%, supporting observation when strict criteria are met. The authors emphasize that surgery should be viewed as part of the treatment pathway, not an isolated technical goal, and they highlight unresolved questions about the survival benefit of more extensive resection.
The review also points to emerging therapies, including GD2-targeting monoclonal antibodies, chimeric antigen receptor T-cell therapy, and inhibitors for ALK mutations, which hold promise for more personalized treatment. However, the authors stress that survival is not the only endpoint: fertility, hearing, endocrine health, cognition, emotional well-being, and secondary cancers require lifelong follow-up as more children survive neuroblastoma.
This risk-based framework offers a practical roadmap for pediatric specialists, supporting more consistent decisions about when to observe, biopsy, operate, or intensify therapy. Wider use of structured surgical reports could improve international trial comparisons, especially where the true extent of resection remains uncertain. As the authors note, neuroblastoma cannot be managed with a single formula; the safest and most effective plan depends on seeing the child's age, tumor biology, anatomical risk, and likely treatment response as one connected picture.
