Neuroblastoma, the most common solid tumor outside the brain in children under five, 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 that integrates diagnosis, risk classification, surgery, chemotherapy, immunotherapy, and survivorship, aiming to guide clinicians in tailoring care based on individual tumor biology.
The review, authored by specialists from the Royal Hospital for Children in Glasgow and the University of Liverpool, highlights that outcomes depend not only on tumor stage but also on age, histology, chromosomal changes, and molecular features such as MYCN amplification. Approximately 70% of patients present with abdominal disease, and 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 add critical prognostic information. MYCN amplification, found in about 25% of tumors and 40-50% of high-risk cases, signals aggressive behavior and guides treatment intensity.
Treatment approaches range from observation or surgery alone for low-risk patients to intensive multimodal therapy for high-risk disease, including chemotherapy, surgery, myeloablative therapy, autologous stem cell rescue, radiotherapy, GD2-targeting monoclonal antibodies, and retinoic acid. For carefully selected infants, a prospective study reported 10-year event-free survival of 94.7% and overall survival of 97.4% with observation alone, supporting a 'watch-and-wait' strategy when strict criteria are met. The authors also address unresolved controversies, such as the role of CT versus MRI in surgical planning and the survival benefit of more extensive resection. They advocate for standardized surgical reporting to improve future trials.
The review emphasizes that neuroblastoma cannot be managed with a single formula. The safest and most effective plan depends on viewing the child's age, tumor biology, anatomical risk, and likely treatment response as one connected picture. For some infants, close observation may be preferable to immediate intervention; for high-risk disease, coordinated multimodal care and emerging therapies are essential. Surgery should be seen as part of the treatment pathway, not an isolated technical goal.
This risk-based framework has practical implications for surgeons, oncologists, radiologists, pathologists, and multidisciplinary tumor boards. It supports more consistent decisions about when to observe, biopsy, operate, or intensify therapy. Wider use of structured surgical reports could enhance international trial comparisons, especially where the true extent of resection is uncertain. The discussion of novel therapies, including GD2-targeting antibodies, CAR T-cell therapy, ALK inhibitors, and telomere biology, points toward more personalized treatment. Importantly, the authors stress that survival is not the only endpoint: fertility, hearing, endocrine health, cognition, emotional well-being, and secondary cancers require lifelong follow-up as more children survive neuroblastoma. These priorities should shape both clinical protocols and future trial design.
