Neuroblastoma, the most common solid tumor outside the brain in children under five, remains one of the most challenging childhood cancers due to its unpredictable behavior. A new narrative review published in the World Journal of Pediatric Surgery offers a comprehensive framework for risk-guided care, integrating diagnosis, risk classification, surgery, chemotherapy, immunotherapy, and survivorship. The review underscores that outcomes depend not only on tumor stage but also on age, histology, chromosomal changes, and molecular features such as MYCN amplification.
The disease 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, authored by specialists from the Royal Hospital for Children in Glasgow and the University of Liverpool, synthesizes current evidence on clinical presentation, imaging, pathology, molecular biology, staging, and treatment. It emphasizes the need to balance treatment intensity against surgical risk, organ preservation, toxicity, and future quality of life.
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 occurs in roughly one-quarter of tumors and in 40-50% of high-risk cases, signaling aggressive behavior.
Treatment ranges from observation or surgery alone in selected low-risk patients to intensive multimodal therapy for high-risk disease, including chemotherapy, surgery, myeloablative therapy, autologous stem cell rescue, radiotherapy, GD2-targeting monoclonal antibodies, and retinoic acid. 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 highlight unresolved questions, such as the role of CT versus MRI in defining surgical anatomy and the survival benefit of more extensive resection. They advocate for standardized surgical reporting to improve international trial comparisons. The review also discusses emerging targeted therapies, including GD2-targeting monoclonal antibodies, chimeric antigen receptor T-cell therapy, and mutations in the ALK gene, pointing toward more personalized treatment.
The central message is that neuroblastoma cannot be managed with a single formula. The safest and most effective plan depends on viewing the child's age, tumor biology, anatomical risk, and likely treatment response as one connected picture. For some infants, this may mean close observation rather than immediate intervention; for high-risk disease, it means coordinated multimodal care and careful surgical judgment.
The review serves as a valuable resource for surgeons, oncologists, radiologists, pathologists, and multidisciplinary tumor boards. Its risk-based framework can support more consistent decisions about when to observe, biopsy, operate, or intensify therapy. 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 comprehensive approach has the potential to shape clinical protocols and future trial design, ultimately improving outcomes and quality of life for children with this complex disease. For more details, the full review is available at https://doi.org/10.1136/wjps-2025-001127.
