Neuroblastoma, the most common extracranial solid tumor in children, presents a clinical paradox: some tumors regress spontaneously, while others are highly aggressive and resistant to therapy. A new narrative review published in the World Journal of Pediatric Surgery (DOI: 10.1136/wjps-2025-001127) offers a comprehensive framework for risk-guided management, aiming to help clinicians tailor treatment to each child's specific disease biology.
The review, authored by specialists from the Royal Hospital for Children in Glasgow and the University of Liverpool, synthesizes current evidence on diagnosis, risk classification, multimodal treatment, and survivorship. It highlights that neuroblastoma outcomes are influenced by a combination of factors, including patient age, tumor histology, chromosomal abnormalities, and molecular markers such as MYCN amplification. Approximately 25% of tumors harbor MYCN amplification, and this feature is present in 40–50% of high-risk cases, where it correlates with aggressive behavior.
The risk stratification system, known as the International Neuroblastoma Risk Group Staging System (INRGSS), uses imaging findings and image-defined risk factors (IDRFs) to categorize disease before treatment. This system helps distinguish localized, metastatic, and special metastatic forms, guiding initial management. For low-risk patients, especially infants, observation or surgery alone may be sufficient, with a reported 10-year event-free survival of 94.7% and overall survival of 97.4% in carefully selected cases. In contrast, high-risk disease requires intensive multimodal therapy, including chemotherapy, surgery, myeloablative therapy with autologous stem cell rescue, radiotherapy, GD2-targeting monoclonal antibodies, and retinoic acid.
The review also addresses ongoing controversies, such as the role of computed tomography (CT) versus magnetic resonance imaging (MRI) in surgical planning, and the survival benefit of more extensive tumor resection. The authors advocate for standardized surgical reporting to improve the reliability of clinical trials and comparisons across institutions.
Dr. [Name], lead author of the review, emphasized that neuroblastoma cannot be managed with a single treatment 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," he said. "For some infants, close observation is preferable to immediate intervention; for high-risk disease, coordinated multimodal care and careful surgical judgment are essential to control the tumor without adding avoidable harm."
The review underscores that surgery is one component of a complex treatment pathway, not an isolated technical goal. It also highlights emerging therapies, including chimeric antigen receptor T-cell therapy, ALK inhibitors, and telomere biology-based approaches, which hold promise for more personalized treatment.
Beyond survival, the authors stress the importance of long-term follow-up for survivors, addressing issues such as fertility, hearing loss, endocrine dysfunction, cognitive deficits, and secondary cancers. These considerations should shape clinical protocols and future trial design.
This risk-based framework provides a practical roadmap for pediatric oncologists, surgeons, radiologists, and pathologists, supporting more consistent decisions about when to observe, biopsy, operate, or intensify therapy. By integrating molecular biology with surgical judgment, the review aims to improve outcomes for children with neuroblastoma while minimizing unnecessary treatment and long-term morbidity.
