Neuroblastoma, the most common solid tumor outside the brain in children under five, presents a clinical paradox: some tumors regress spontaneously, while others are relentlessly aggressive. A new narrative review published in the World Journal of Pediatric Surgery (DOI: 10.1136/wjps-2025-001127) offers a comprehensive framework that integrates diagnosis, risk classification, and multimodal treatment, aiming to guide pediatric specialists in personalizing care for this unpredictable disease.
The review, authored by specialists from the Royal Hospital for Children in Glasgow and the University of Liverpool, synthesizes current evidence on neuroblastoma's clinical presentation, imaging, pathology, and molecular biology. It underscores that outcomes hinge not solely on tumor stage but on a constellation of factors: patient age, histology, chromosomal aberrations, and molecular markers such as MYCN amplification. These elements determine whether a child is best served by observation, surgery, or intensive multimodality therapy.
Neuroblastoma accounts for approximately 15% of pediatric cancer deaths, yet five-year survival exceeds 90% for low- and intermediate-risk disease, dropping below 60% for high-risk cases. The challenge lies in balancing treatment intensity against potential harm—surgical risk, organ preservation, toxicity, and long-term quality of life. The review emphasizes that pretreatment risk assessment shapes every step of care, from initial diagnosis to survivorship.
About 70% of patients present with abdominal disease. Diagnosis typically combines urine catecholamine testing, magnetic resonance imaging (MRI), meta-iodobenzylguanidine (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, while molecular markers add prognostic precision. MYCN amplification, present in roughly one-quarter of tumors and 40–50% of high-risk cases, signals aggressive behavior.
For carefully selected infants, observation alone can achieve excellent outcomes. A prospective study reported 10-year event-free survival of 94.7% and overall survival of 97.4% in infants monitored without immediate intervention, supporting a 'watch-and-wait' approach when strict criteria are met. In contrast, high-risk disease demands coordinated multimodal therapy: chemotherapy, surgery, myeloablative therapy with autologous stem cell rescue, radiotherapy, GD2-targeting monoclonal antibodies, and retinoic acid.
The review also highlights unresolved controversies. Computed tomography (CT) may better define surgical anatomy in some high-risk abdominal tumors than MRI, yet the survival benefit of more extensive resection remains debated. Standardized surgical reporting could improve future trials by distinguishing complete resection from incomplete removal more reliably.
The authors stress that 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,' they write. For some infants, that may mean close observation rather than immediate intervention; for high-risk disease, it means coordinated care where surgery is viewed as one part of the pathway, not an isolated technical goal.
Emerging therapies, including GD2-targeting antibodies, chimeric antigen receptor T-cell therapy, and agents targeting ALK mutations or telomere biology, point toward more personalized treatment. The review also emphasizes that survival is not the only endpoint. As more children survive neuroblastoma, long-term follow-up must address fertility, hearing, endocrine health, cognition, emotional well-being, and secondary cancers.
This risk-based framework offers a practical roadmap for surgeons, oncologists, radiologists, pathologists, and multidisciplinary tumor boards. By clarifying when to observe, biopsy, operate, or intensify therapy, it supports more consistent decision-making. Wider adoption of structured surgical reports could enhance international trial comparisons, especially where the extent of resection is uncertain. The review's insights are poised to shape both clinical protocols and future research, ultimately improving outcomes for children facing this complex disease.
