Risk-Guided Care Reshapes Childhood Neuroblastoma Treatment

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 offers a unified framework for managing this disease, integrating diagnosis, risk classification, and multimodal treatment. The review underscores that outcomes hinge on more than tumor stage; age, histology, chromosomal aberrations, and molecular markers such as MYCN amplification are equally critical.

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 treatment. It highlights that about 70% of patients present with abdominal disease, and diagnosis typically involves urine catecholamine testing, MRI, MIBG scintigraphy, bone marrow assessment, biopsy, and genetic profiling. The International Neuroblastoma Risk Group Staging System (INRGSS) uses image-defined risk factors (IDRFs) to classify disease before treatment, aiding in risk stratification.

Molecular profiling adds another layer of precision. MYCN amplification, present in roughly a quarter of tumors and 40-50% of high-risk cases, signals aggressive behavior and guides therapy intensity. Treatment strategies range from observation or surgery alone for low-risk patients to intensive multimodal regimens for high-risk disease, including chemotherapy, surgery, myeloablative therapy, autologous stem cell rescue, radiotherapy, and immunotherapy with GD2-targeting monoclonal antibodies and retinoic acid. For carefully selected infants, observation alone has yielded impressive outcomes: a prospective study reported 10-year event-free survival of 94.7% and overall survival of 97.4%, validating this approach when strict criteria are met.

The review also addresses unresolved controversies, such as the role of extensive surgical resection in high-risk abdominal tumors and the comparative utility of CT versus MRI in defining surgical anatomy. Standardized surgical reporting is advocated to improve consistency in clinical trials and distinguish complete from incomplete resection more reliably.

The authors emphasize that neuroblastoma cannot be managed with a one-size-fits-all approach. They state, "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." For some infants, close observation may be preferable to immediate intervention; for high-risk disease, coordinated multimodal care and careful surgical judgment are essential. Surgery should be viewed as part of the treatment pathway, not an isolated technical goal.

This risk-based framework is invaluable for surgeons, oncologists, radiologists, pathologists, and tumor boards. It supports more consistent decisions about when to observe, biopsy, operate, or intensify therapy. The discussion of emerging therapies, including GD2-targeting antibodies, CAR T-cell therapy, ALK inhibitors, and telomere biology, points toward more personalized treatment. Moreover, the authors stress that survival is not the only endpoint; long-term health issues such as fertility, hearing, endocrine function, cognition, and secondary cancers require lifelong follow-up as survival rates improve.

This review serves as a practical roadmap for tailoring care, avoiding unnecessary treatment in low-risk disease, and improving decision-making for high-risk neuroblastoma, ultimately shaping both clinical protocols and future research.