Neuroblastoma, the most common solid tumor outside the brain in children under five, presents a clinical paradox: some tumors vanish without treatment, while others resist even the most intensive therapies. A new narrative review, published in the World Journal of Pediatric Surgery (DOI: 10.1136/wjps-2025-001127), synthesizes current evidence to provide a comprehensive framework for managing this unpredictable disease.
The review, authored by specialists from the Royal Hospital for Children in Glasgow and the University of Liverpool, integrates diagnosis, risk classification, surgery, chemotherapy, immunotherapy, and survivorship into a single clinical pathway. It underscores that outcomes are shaped by more than just tumor stage—age, histology, chromosomal changes, and molecular features like MYCN amplification all play critical roles.
Neuroblastoma accounts for about 15% of pediatric cancer deaths, yet five-year survival exceeds 90% for low- and intermediate-risk cases. For high-risk patients, survival drops below 60%. This stark disparity drives the need for precise, risk-adapted strategies that balance treatment intensity against toxicity and long-term quality of life.
According to the review, about 70% of patients present with abdominal disease. 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-defined risk factors to classify disease before treatment, while molecular markers like MYCN amplification—found in 40-50% of high-risk cases—signal aggressive biology.
Treatment ranges from observation alone in select infants to intensive multimodal therapy for high-risk disease. For carefully selected infants, a prospective study cited in the review reported 10-year event-free survival of 94.7% and overall survival of 97.4%, supporting a watch-and-wait approach when strict criteria are met.
The authors highlight unresolved controversies, including whether CT or MRI better defines surgical anatomy in high-risk abdominal tumors and whether more extensive resection improves survival. They advocate for standardized surgical reporting to improve trial comparisons.
The review's central message is that neuroblastoma cannot be managed with a one-size-fits-all 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,” the authors write. They emphasize that surgery is one part of a coordinated pathway, not an isolated technical goal.
For the medical community, this risk-based framework offers practical guidance for multidisciplinary tumor boards, helping clinicians decide when to observe, biopsy, operate, or intensify therapy. The discussion of emerging therapies—including GD2-targeting monoclonal antibodies, CAR T-cell therapy, ALK mutations, and telomere biology—points toward more personalized treatment.
Importantly, the authors stress that survival is not the only endpoint. As more children survive neuroblastoma, long-term follow-up for fertility, hearing, endocrine health, cognition, and secondary cancers becomes essential. This holistic perspective could shape future clinical protocols and trial design, ensuring that children not only live but thrive after treatment.
