Neuroblastoma, the most common solid tumor outside the brain in children under five, presents a clinical paradox: some tumors vanish without treatment, while others are relentlessly aggressive. A new narrative review published in the World Journal of Pediatric Surgery (DOI:10.1136/wjps-2025-001127) aims to bring clarity to this complexity by synthesizing current evidence into a single, risk-guided framework for diagnosis, treatment, and survivorship.
The review, authored by specialists from the Royal Hospital for Children in Glasgow and the University of Liverpool, underscores that outcomes depend not only on tumor stage but also on age, histology, chromosomal changes, and molecular features such as MYCN amplification. MYCN amplification occurs in roughly one-quarter of tumors and in 40-50% of high-risk cases, signaling aggressive behavior. The International Neuroblastoma Risk Group Staging System (INRGSS) uses imaging findings and image-defined risk factors to classify disease before treatment, aiding in risk stratification.
Treatment strategies vary dramatically based on risk. For low-risk infants, observation or surgery alone may suffice. A prospective study cited in the review reported 10-year event-free survival of 94.7% and overall survival of 97.4% for carefully selected infants monitored without immediate intervention. For high-risk disease, multimodal therapy including chemotherapy, surgery, myeloablative therapy, autologous stem cell rescue, radiotherapy, GD2-targeting monoclonal antibodies, and retinoic acid is often necessary. However, five-year survival for high-risk cases remains below 60%, highlighting the need for refined approaches.
The authors emphasize that surgery is just one part of the treatment pathway, not an isolated goal. They highlight ongoing controversies, such as the role of computed tomography (CT) versus magnetic resonance imaging (MRI) in defining surgical anatomy, and the survival benefit of more extensive resection. Standardized surgical reporting could improve future trial comparisons and help distinguish complete from incomplete resection.
The review also points toward more personalized therapies, including GD2-targeting monoclonal antibodies, chimeric antigen receptor T-cell therapy, and targeting mutations in the anaplastic lymphoma kinase (ALK) gene. These emerging treatments offer hope but must be balanced against long-term side effects. Survivors face risks of fertility issues, hearing loss, endocrine dysfunction, cognitive deficits, and secondary cancers, necessitating lifelong follow-up.
This risk-based framework is designed to support multidisciplinary teams in making consistent decisions about when to observe, biopsy, operate, or intensify therapy. By integrating molecular biology with clinical presentation, the review provides a practical roadmap for tailoring care while avoiding unnecessary treatment in low-risk disease and improving decision-making for high-risk patients.
The full review is available at https://doi.org/10.1136/wjps-2025-001127.
