What is the recommended staging and treatment approach for adrenal neuroblastoma in an adult patient?

Neuroblastoma of the Adrenals in Adults

Adult adrenal neuroblastoma should be staged using the International Neuroblastoma Risk Group (INRG) staging system and treated with complete surgical resection as the primary curative approach, followed by risk-adapted multimodal therapy based on stage and disease characteristics.

Staging Approach

Use the INRG Staging System for all adult neuroblastoma patients 1, 2. This system classifies disease as:

• L1: Localized tumor without Image-Defined Risk Factors (IDRFs), confined to one body compartment
• L2: Locoregional tumor with one or more IDRFs present
• M: Distant metastatic disease
• MS: Only applicable to children <18 months (not relevant for adults)

Essential Staging Workup

Complete the following before initiating treatment 1:

• 123I-MIBG imaging (detects up to 90% of neuroblastomas via norepinephrine transporter uptake)
• 18F-FDG-PET if MIBG-nonavid or mixed-avidity disease suspected
• CT or MRI of abdomen and chest
• Bone marrow biopsy if metastatic disease suspected
• Urinary catecholamines (though only 40% of adult cases show elevation 3)
• MYCN amplification testing (rarely positive in adults but prognostically important)

Critical caveat: Adults with neuroblastoma have different biology than children—lower rates of elevated catecholamines (40% vs >90%), virtually no MYCN amplification, but paradoxically worse outcomes 3.

Treatment Algorithm

Localized Disease (L1)

Surgery plus radiation therapy achieves superior progression-free survival (11.1 months) compared to single-modality treatment (5-6 months, P=0.07) 2.

• Perform complete surgical resection (R0 resection) as primary treatment
• Add adjuvant radiation therapy to tumor bed
• Consider observation alone only for completely resected, low-risk tumors

Locoregional Disease (L2)

Multimodal therapy is required:

• Neoadjuvant chemotherapy to reduce tumor burden and facilitate resection
• Complete surgical resection targeting >90% tumor removal
• Adjuvant radiation therapy to tumor bed, especially if incomplete resection (R1/Rx)

The evidence shows median PFS of 5.2 months with local therapy alone vs 4 months with added chemotherapy (P=0.23), suggesting both are necessary but insufficient 2.

Metastatic Disease (M)

Prognosis is dismal with 5-year survival of only 7% in adolescents/adults vs 30% in younger children 3. Treatment priorities shift to disease control and quality of life:

1. First-line for MIBG-avid disease: 131I-MIBG radiotherapy (5.5-38 GBq)

   • 22-47% objective response rates
   • Long-term survival of responders: 4.7 years 4
   • Best for soft tissue metastases, limited bone involvement

2. Systemic chemotherapy for MIBG-nonavid or rapidly progressive disease:

   • CVD regimen (cyclophosphamide, vincristine, dacarbazine)
   • CVDD or CDD (adding doxorubicin)
   • 40% clinical benefit rate, 25% tumor reduction 4

3. Surgical debulking if anatomically feasible to reduce hormone secretion and improve subsequent therapy efficacy

4. Locoregional therapies: Embolization, radiofrequency ablation for selected metastases

5. Palliative radiation for painful bone metastases 4

Critical Management Principles

Do not biopsy potentially resectable adrenal tumors—this is potentially harmful and not informative; proceed directly to surgical resection 4.

Expect multiple recurrences and chronic disease: Adult neuroblastoma follows an indolent but relentless course with 94% recurrence rate and median survival of 30% at 5 years despite treatment 3. Patients often experience long courses with multiple recurrences before death.

Surveillance Protocol

After Complete Resection

• Every 3 months for first 2 years: Abdominal CT/MRI, chest CT, urinary catecholamines (if initially elevated) 4
• Gradually increase intervals after 2 years
• Continue for minimum 10 years due to late recurrence risk 4

Metastatic/Inoperable Disease

• Every 2-4 months during first year, then adjust based on disease behavior 4
• Include functional imaging (MIBG or FDG-PET) with anatomic imaging

Key Differences from Pediatric Disease

Adult neuroblastoma demonstrates 3, 5:

• Lower catecholamine elevation rates (40% vs >90%)
• Virtually absent MYCN amplification (0-3% vs 20-25%)
• Higher proportion of metastatic disease at diagnosis (76%)
• Significantly worse survival despite similar staging
• Longer time to progression but ultimately poor outcomes

The bottom line: Despite using pediatric staging systems and adapted pediatric protocols, adult neuroblastoma behaves as a distinct, more aggressive entity requiring maximal surgical effort combined with multimodal therapy, yet outcomes remain poor regardless of stage 2, 3, 5.