Neuroblastoma, the most common solid tumor outside the brain in children under five, presents a clinical paradox: some tumors regress spontaneously while others are relentlessly aggressive. This unpredictability has long challenged pediatric oncologists. A new narrative review, published in the World Journal of Pediatric Surgery, offers a comprehensive framework that integrates diagnosis, risk classification, surgery, chemotherapy, immunotherapy, and survivorship, aiming to tailor treatment to each child's specific disease profile.
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 molecular biology. It underscores that outcomes are influenced not only by tumor stage but also by age, histology, chromosomal changes, and molecular features such as MYCN amplification. These factors guide whether a child should undergo observation, surgery, or intensive multimodality therapy.
Approximately 70% of patients present with abdominal disease. 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 findings and image-defined risk factors (IDRFs) to classify disease before treatment. Molecular markers add critical insight: MYCN amplification, found in about 25% of tumors and 40-50% of high-risk cases, signals aggressive behavior.
Treatment strategies range from observation alone in carefully selected infants to aggressive multimodal therapy for high-risk disease. For low-risk patients, surgery may be curative, while high-risk patients require chemotherapy, surgery, myeloablative therapy with autologous stem cell rescue, radiotherapy, GD2-targeting monoclonal antibodies, and retinoic acid. The review highlights a prospective study reporting 10-year event-free survival of 94.7% and overall survival of 97.4% in infants managed with observation under strict criteria, supporting a less-is-more approach in select cases.
The authors address unresolved controversies, such as the role of extensive surgical resection. While CT may better define surgical anatomy in some high-risk abdominal tumors, the survival benefit of more aggressive resection remains debated. They advocate for standardized surgical reporting to improve comparisons across trials, distinguishing complete from incomplete resection more reliably.
“Neuroblastoma cannot be managed with a single formula,” the authors 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 new therapies are essential to control the tumor while minimizing harm.
The review serves as a practical roadmap for pediatric surgeons, oncologists, radiologists, pathologists, and multidisciplinary tumor boards. Its risk-based framework supports 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 approaches.
Importantly, the authors stress that survival is not the only endpoint. As more children survive neuroblastoma, long-term follow-up is crucial to address fertility, hearing, endocrine health, cognition, emotional well-being, and secondary cancers. These priorities should shape both clinical protocols and future trial designs.
