What is the best management approach for an elderly man with metastatic melanoma in the right axillary lymph nodes?

Management of Elderly Man with Metastatic Melanoma in Right Axillary Lymph Nodes

For an elderly man with 2 out of 2 right axillary lymph nodes positive for metastatic melanoma, the optimal management is complete lymph node dissection followed by systemic immunotherapy with combination ipilimumab plus nivolumab (if BRAF wild-type) or consideration of BRAF/MEK inhibitors (if BRAF-mutated), with treatment selection based on performance status, comorbidities, and disease burden rather than chronological age alone. 1, 2

Initial Staging and Molecular Testing

• Mandatory BRAF mutation testing must be performed immediately, as this determines the systemic therapy approach and has critical implications for treatment selection 1, 2
• Complete staging workup including CT chest/abdomen/pelvis and brain MRI to identify distant metastases and confirm stage III disease versus stage IV 1
• Assess LDH levels, performance status (ECOG), and rate of disease progression as these are key prognostic factors 2
• Evaluate for additional nodal disease or in-transit metastases that may alter surgical planning 3

Surgical Management

Complete axillary lymph node dissection should be performed with the goal of removing at least 10 lymph nodes to achieve adequate staging and locoregional control. 3

• The presence of 2/2 positive nodes indicates clinically evident nodal disease (stage IIIB or IIIC depending on primary tumor characteristics) 3
• Sentinel lymph node biopsy is not applicable here as the patient already has known positive nodes 3
• Complete (R0) resection is the surgical goal for all resectable disease 1, 2

Adjuvant Radiation Therapy Consideration

• Consider adjuvant radiation following lymphadenectomy for patients with clinically positive nodes, though this remains controversial (category 2B recommendation) 3
• The decision should weigh the high risk of nodal relapse against potential toxicity in an elderly patient 3
• Radiation may be particularly relevant if there are adverse features such as extracapsular extension or multiple positive nodes 3

Systemic Therapy Selection

For BRAF Wild-Type Disease:

Combination immunotherapy with ipilimumab plus nivolumab followed by nivolumab maintenance is the preferred first-line option, achieving durable responses in 45-50% of patients with 10-year overall survival of 43%. 1, 2, 4

• Alternative single-agent options (pembrolizumab or nivolumab monotherapy) should be considered if combination therapy is contraindicated due to comorbidities or frailty 1, 2
• The elderly can tolerate immunotherapy effectively, though careful monitoring for immune-related adverse events is essential 5

For BRAF-Mutated Disease:

The choice between immunotherapy and targeted therapy (BRAF/MEK inhibitor combinations) depends on specific clinical characteristics: 1

• Immunotherapy first is preferred for patients with favorable prognostic features (good performance status, normal LDH, slow disease progression) as it offers potential for long-term durable control 1, 2
• Targeted therapy first (dabrafenib plus trametinib or other BRAF/MEK combinations) should be considered for patients with poor prognostic features, rapid disease progression, or high disease burden, as it achieves response rates of approximately 70% with rapid onset 3, 1

Special Considerations for Elderly Patients

• Treatment decisions should be based on functional status, comorbidities, and performance status rather than chronological age alone 3, 6
• Geriatric assessment may help identify patients who can tolerate aggressive therapy versus those requiring modified approaches 3
• Both immunotherapy and targeted therapy have shown efficacy and tolerability in older patients with melanoma 5
• Elderly patients with melanoma often present with more aggressive biological features and more locally advanced tumors 6

Treatment Duration and Monitoring

• Continue pembrolizumab for up to 24 months or nivolumab beyond 2 years if ongoing response 2
• For patients achieving complete response after ≥6 months of anti-PD-1 therapy, stopping treatment can be considered with 85-90% remaining disease-free 2
• Tumor assessments should be conducted every 6-12 weeks initially, then every 12 weeks thereafter 4

Critical Pitfalls to Avoid

• Do not delay systemic therapy in patients with favorable prognostic features, as this represents a missed opportunity for long-term durable control with immunotherapy 1
• Do not use single-agent BRAF inhibition; combination BRAF/MEK inhibition is the standard for targeted therapy 1
• Do not assume elderly patients cannot tolerate aggressive therapy based solely on age; functional assessment is more predictive 3, 5
• Do not perform incomplete lymph node dissection when complete dissection is feasible, as adequate staging requires at least 10 nodes 3
• Do not use chemotherapy (dacarbazine, temozolomide) as first-line treatment when modern immunotherapy and targeted therapy options are available, as chemotherapy has response rates less than 20% 3, 1