Neuroblastoma, the most common solid tumor outside the brain in children under five, presents a formidable challenge due to its highly variable 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 risk-guided approach that integrates diagnosis, classification, surgery, chemotherapy, immunotherapy, and survivorship. This framework aims to tailor care to each child's specific risk profile, thereby improving outcomes and minimizing unnecessary treatment.
The review highlights that neuroblastoma accounts for about 15% of pediatric cancer deaths, with five-year survival exceeding 90% for low- and intermediate-risk disease but falling below 60% for high-risk cases. The key to improving these statistics lies in accurate risk stratification, which now incorporates not only tumor stage but also age, histology, chromosomal abnormalities, and molecular markers such as MYCN amplification. About 70% of patients present with abdominal tumors, 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 imaging findings and image-defined risk factors (IDRFs) to classify disease before treatment, enabling a more precise assessment of surgical risk and resectability.
The treatment paradigm ranges from observation alone for carefully selected infants to intensive multimodal therapy for high-risk disease. For low-risk patients, surgery alone may be curative, while high-risk patients require a combination of chemotherapy, surgery, myeloablative therapy with autologous stem cell rescue, radiotherapy, and immunotherapy with anti-GD2 monoclonal antibodies and retinoic acid. The review cites a prospective study where observation in selected infants yielded a 10-year event-free survival of 94.7% and overall survival of 97.4%, supporting a watchful waiting approach when strict criteria are met. Conversely, for high-risk disease, coordinated multimodal care is essential, and surgery should be viewed as one component of the treatment pathway rather than an isolated technical goal.
The authors emphasize that neuroblastoma cannot be managed with a single formula. Instead, the safest and most effective plan depends on viewing the child's age, tumor biology, anatomical risk, and likely treatment response as a connected whole. For some infants, close observation rather than immediate intervention is appropriate; for high-risk patients, careful surgical judgment and novel therapies are needed to control the tumor without adding avoidable harm. The review also addresses unresolved questions, such as the role of computed tomography (CT) in defining surgical anatomy and the survival benefit of more extensive resection. Standardized surgical reporting could help future trials distinguish complete from incomplete resection more reliably.
The review is a valuable resource for surgeons, oncologists, radiologists, pathologists, and multidisciplinary tumor boards. Its risk-based framework supports more consistent decisions about when to observe, biopsy, operate, or intensify therapy. The discussion of emerging targeted therapies, including GD2-targeting monoclonal antibodies, chimeric antigen receptor 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 effects on 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.
