Treatment of Axillary Nodal Metastasis from Melanoma
Radical axillary lymph node dissection (complete levels I-III) is the recommended surgical treatment for clinically-detected axillary nodal metastases from melanoma, followed by consideration of adjuvant systemic therapy with anti-PD-1 immunotherapy (nivolumab or pembrolizumab) or BRAF/MEK inhibitors if BRAF V600 mutation-positive. 1
Surgical Management
Complete Lymph Node Dissection is Standard
Perform radical axillary lymph node dissection (levels I-III) rather than "node picking" (removal of only clinically apparent nodes). 1 The ESMO consensus conference explicitly recommends against limited dissection because the number of involved lymph nodes in clinically-detected disease is significantly greater than in sentinel node-positive disease, and the location of additional involved nodes cannot be accurately predicted. 1
Include level III axillary nodes in all patients with palpable axillary disease. 2 Level III nodes are positive in approximately 17% of melanoma patients with palpable axillary disease, and their involvement provides important prognostic information for overall survival. 2 In contrast, level III nodes are essentially never positive (0%) in patients with only sentinel node-positive disease. 3
Preoperative Requirements
Obtain pathological confirmation (cytology or histology) before proceeding with lymphadenectomy. 1 Fine needle aspiration biopsy cytology is a useful technique for confirming axillary metastasis preoperatively. 4
Complete adequate staging workup before surgery to exclude distant metastatic disease, as this would fundamentally change the treatment approach. 1
Adjuvant Systemic Therapy
Stage III Disease After Complete Resection
Offer adjuvant anti-PD-1 immunotherapy (nivolumab or pembrolizumab) as first-line adjuvant treatment. 5, 6 These agents have demonstrated superior efficacy compared to historical interferon-alpha therapy with better tolerability. 5
For BRAF V600 mutation-positive melanomas, consider dabrafenib plus trametinib as an alternative adjuvant option. 5 BRAF mutation testing is mandatory before finalizing the adjuvant treatment plan. 5
Do NOT use adjuvant chemotherapy (dacarbazine, temozolomide) or interferon-alpha as standard treatment. 5 Chemotherapy has shown no survival benefit in the adjuvant setting, and interferon has been superseded by anti-PD-1 therapy due to inconsistent results and considerable toxicity. 5
Adjuvant Radiotherapy Considerations
Limited Role in Standard Cases
- Adjuvant radiotherapy is NOT routinely recommended after complete axillary lymph node dissection with clear margins. 5, 7 There is no role for radiotherapy after complete excision with adequate margins in standard cases. 5
Specific High-Risk Indications
Consider hypofractionated adjuvant radiotherapy (typically 30 Gy in 6 Gy fractions twice weekly) for patients with multiple positive nodes or extracapsular extension. 8 This is a category 2B recommendation based on retrospective data showing 87% 5-year axillary control rates in high-risk patients. 8
Radiotherapy should be considered for incomplete nodal clearance (fixed nodes, extensive invasion, capsular disruption). 7 This is particularly relevant in the head and neck region but applies to axillary disease as well. 1
Predictors of Benefit from Radiotherapy
Patients at highest risk for axillary recurrence (and thus most likely to benefit from adjuvant radiotherapy) include those with: 8
- Axillary disease >6 cm in size
- ≥4 positive lymph nodes
- Extracapsular extension
- Recurrent disease after initial surgical resection
Management of the Primary Melanoma
If the primary melanoma is still present, perform wide local excision with 1 cm margins for melanomas ≤2 mm Breslow thickness or 2 cm margins for melanomas >2 mm thickness. 5 Primary closure without reconstruction is preferred whenever possible. 1
In the context of stage IV disease (distant metastases), there is no need to resect the primary tumor unless symptomatic or tissue is needed for diagnosis. 1 If resection is indicated, use clear margins without additional safety margins. 1
Common Pitfalls to Avoid
Do not perform limited "node picking" procedures. 1 Complete dissection is required because drainage patterns are highly variable and additional involved nodes cannot be reliably predicted by imaging. 1
Do not omit level III dissection in patients with palpable axillary disease. 2 Unlike breast cancer, where level III can sometimes be spared, melanoma requires complete basin dissection due to unpredictable drainage patterns. 1
Do not use outdated adjuvant therapies (chemotherapy, interferon-alpha, hormone therapy). 5 Modern immunotherapy with anti-PD-1 agents is superior and should be the standard approach. 5
Do not fail to test for BRAF mutations. 5 This is mandatory for treatment selection in both the adjuvant and metastatic settings. 5
Expected Outcomes and Toxicity
Arm lymphedema occurs in approximately 40% of patients after axillary dissection with or without radiotherapy. 8 Grade 1 (transient/asymptomatic) edema occurs in 21%, Grade 2 (requiring medical intervention) in 19%, and Grade 3 (requiring surgical intervention) in only 1% at 5 years. 8
Five-year overall survival after complete resection of palpable axillary disease is approximately 39-50%. 8, 2 Patients with positive level III nodes have significantly worse outcomes (median OS 18.6 months). 2
Axillary recurrence rates after complete dissection with adjuvant radiotherapy are approximately 8-13%. 8, 2 This is substantially better than the 30-50% recurrence risk with surgery alone in high-risk patients. 8