What is the prognosis for a child with neuroblastoma?

Prognosis of Neuroblastoma

The prognosis of neuroblastoma varies dramatically based on risk stratification, with low-risk patients achieving >95% five-year survival, intermediate-risk patients achieving 90-95% five-year survival, and high-risk patients having significantly worse outcomes despite intensive multimodality therapy. 1

Risk-Based Prognostic Stratification

The prognosis is fundamentally determined by risk classification, which integrates multiple clinical and biological factors 1:

Low-Risk Disease (>95% Five-Year Survival)

Children with low-risk neuroblastoma have excellent outcomes with minimal intervention. 1

Key favorable prognostic features include:

• Age <12 months with MS disease, favorable histology, MYCN non-amplified, hyperdiploid tumors without segmental chromosomal aberrations 1
• Localized L1 tumors that are completely resected (regardless of MYCN status) 1
• Ganglioneuroblastoma intermixed and ganglioneuroma subtypes, which carry excellent prognosis 1

Treatment approach and outcomes:

• Surgery alone or observation without biopsy for select infants <6 months with small adrenal masses (≤3.1 cm if solid, ≤5 cm if ≥25% cystic) 2, 3
• No chemotherapy or radiation required for most patients 2
• Five-year survival exceeds 95% 1, 2

Intermediate-Risk Disease (90-95% Five-Year Survival)

Patients whose disease characteristics fall between low-risk and high-risk criteria maintain excellent survival with moderate-intensity chemotherapy. 1

Treatment and outcomes:

• Require 2-8 cycles of cyclophosphamide-based chemotherapy followed by surgical resection 2
• Goal is achieving 50-90% tumor volume reduction before surgery, depending on biology 2
• No radiation routinely indicated 2
• Five-year survival: 90-95% 1, 2

High-Risk Disease (Significantly Worse Prognosis)

High-risk neuroblastoma carries a poor prognosis despite intensive multimodality therapy. 4

Automatic high-risk assignment occurs with:

• MYCN amplification (the strongest independent prognostic risk factor, overriding all other features except completely resected L1 tumors) 1, 2
• Age ≥18 months with stage M disease (regardless of other features) 1, 2
• Age 12-18 months with M or MS disease plus unfavorable histology, segmental chromosomal aberrations, or MYCN amplification 1

Historical outcomes:

• Five-year survival <50% with older treatment approaches 4
• Estimated survival has improved with modern intensive multimodality therapy including immunotherapy with dinutuximab 5, 4

Critical Prognostic Molecular Biomarkers

MYCN amplification is the strongest independent prognostic factor and should be assessed in all neuroblastomas. 1

Additional key prognostic markers include:

• Segmental chromosomal aberrations (SCAs) involving chromosomes 1p, 11q, 3p, 4p, 17q, 1q, or 2p are associated with inferior outcomes 1
• Tumor cell ploidy: DNA index >1 (hyperdiploid) is more favorable than DNA index =1 1
• Histology classification per International Neuroblastoma Pathology Classification distinguishes favorable versus unfavorable histology based on differentiation grade, mitosis-karyorrhexis index, and age 1

Age-Specific Prognostic Considerations

Age at diagnosis is an independent prognostic factor, with infants having significantly better outcomes than older children with the same stage disease. 6, 7

Age-related prognosis:

• Infants <1 year with localized and Stage IVS disease have extremely good prognosis (90% survival), often cured without intensive chemotherapy 6
• Infants <1 year with Stage IV disease have significantly better prognosis (18% survival) than older children with Stage IV disease, though still poor 6
• Children ≥18 months with metastatic disease are automatically high-risk regardless of other features 1, 2

Unique Biological Behaviors Affecting Prognosis

Neuroblastoma exhibits distinctive features that impact prognosis 7, 8:

• Spontaneous regression can occur, particularly in infants with Stage IVS disease 6, 7
• Maturation into benign lesions (ganglioneuroma) is possible 7
• Metastatic patterns typically involve bone, bone marrow, lymph nodes, and liver; spread to lung or brain is rare 7

Critical Prognostic Pitfalls

If MYCN amplification is discovered after incomplete resection in a presumed low-risk patient, immediately reassign to high-risk protocol. 2

Other important caveats:

• Approximately 9% of high-risk patients progress despite intensive induction regimens 2
• Survivors of high-risk neuroblastoma face significantly elevated risks of late morbidity and mortality, including grade 3-5 chronic health conditions, second malignant neoplasms, and treatment-related organ dysfunction 2
• International cooperative groups may use different risk classification criteria than Children's Oncology Group, potentially categorizing the same patient differently 1

Long-Term Considerations

High-risk neuroblastoma survivors require lifelong monitoring for treatment-related complications. 2

Common late effects include:

• Ototoxicity from platinum-based chemotherapy (most high-risk patients experience hearing loss, with 13% developing new or worsening hearing loss after eflornithine) 2
• Cardiac dysfunction requiring serial monitoring 2
• Fertility impairment (preservation should be discussed before chemotherapy when possible) 2
• Second malignancies 2