Neuroblastoma, the most common solid tumor outside the brain in children under five, remains a formidable challenge due to its unpredictable behavior. While some tumors regress spontaneously, others are aggressive and resistant to therapy. A new narrative review published in the World Journal of Pediatric Surgery (DOI:10.1136/wjps-2025-001127) synthesizes current evidence to offer a unified clinical framework for diagnosis, risk classification, surgery, chemotherapy, immunotherapy, and survivorship. The review underscores that outcomes depend on more than just tumor stage; age, histology, chromosomal changes, and molecular features such as MYCN amplification are critical determinants.
Neuroblastoma accounts for about 15% of pediatric cancer deaths. Five-year survival exceeds 90% for low- and intermediate-risk disease but falls below 60% for high-risk cases. Clinicians must balance treatment intensity against surgical risk, organ preservation, toxicity, and future quality of life. The review, authored by specialists from the Royal Hospital for Children in Glasgow and the University of Liverpool, emphasizes that risk assessment guides every step of care. Approximately 70% of patients present with abdominal disease, and diagnosis typically involves urine catecholamine testing, MRI, MIBG scans, bone marrow assessment, biopsy, and genetic profiling.
The International Neuroblastoma Risk Group Staging System (INRGSS) uses imaging-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 alone in selected infants to intensive multimodal therapy for high-risk disease, including chemotherapy, surgery, myeloablative therapy, stem cell rescue, radiotherapy, GD2-targeting monoclonal antibodies, and retinoic acid. For carefully selected infants under observation, a prospective study reported 10-year event-free survival of 94.7% and overall survival of 97.4%, supporting this approach when strict criteria are met.
The authors highlight unresolved surgical questions, such as the role of CT versus MRI in defining anatomy and the survival benefit of more extensive resection. They advocate for standardized surgical reporting to improve trial comparisons. The review also discusses emerging therapies, including GD2-targeting antibodies, CAR T-cell therapy, ALK inhibitors, and telomere biology, pointing toward more personalized treatment. Importantly, the authors stress that survival is not the only endpoint; long-term follow-up is essential to address fertility, hearing, endocrine health, cognition, emotional well-being, and secondary cancers.
This risk-based framework provides a practical roadmap for pediatric specialists, helping to avoid unnecessary treatment in low-risk disease and improve decision-making for high-risk patients. By integrating molecular biology with clinical staging, the review supports more consistent, individualized care and highlights priorities for future research and trial design.
