In a patient with a primary melanoma of the right toe staged pT4bN0M0 (tumor >4 mm with ulceration, no nodal involvement, no distant metastasis), what is the recommended next management?

Management of pT4bN0M0 Right Toe Melanoma

For a pT4bN0M0 melanoma (>4mm with ulceration, node-negative), proceed immediately with wide local excision using 2 cm margins, perform sentinel lymph node biopsy despite negative clinical nodes, and strongly consider adjuvant immunotherapy with nivolumab or pembrolizumab given the high-risk features of ulceration and thick tumor. 1, 2, 3

Surgical Management Priority

Wide Local Excision

• Execute a 2 cm margin excision for this >4 mm thick melanoma 1, 4
• For toe melanomas specifically, modifications to preserve function are acceptable, but margins should not be compromised below 1 cm if anatomically feasible 1
• Excision depth should extend to (but not including) the fascia 1
• In some anatomically constrained acral sites, 3 cm margins have historically been recommended for melanomas >4 mm, though 2 cm is now the standard 1

Sentinel Lymph Node Biopsy - Mandatory

• SLNB is absolutely mandatory in this case despite N0 clinical staging 2, 4
• Ulceration is an independent indication for SLNB regardless of thickness 2
• The presence of ulceration in a T4b melanoma creates approximately 20% risk of occult nodal metastases 5
• SLNB must be performed before wide excision, ideally in the same operative setting 1
• This should only be performed by experienced surgical teams 1, 2

Adjuvant Systemic Therapy - Strongly Recommended

Stage IIC Disease Requires Adjuvant Treatment

• This pT4bN0M0 melanoma is classified as Stage IIC (>4 mm with ulceration, node-negative) 1, 4
• Adjuvant anti-PD-1 immunotherapy significantly improves recurrence-free survival in Stage IIB-C melanoma 3

Specific Adjuvant Options

• Nivolumab 480 mg IV every 4 weeks for up to 1 year reduces recurrence risk (HR 0.42,95% CI 0.30-0.59, p<0.0001) in Stage IIB/C disease 6, 3
• Pembrolizumab similarly improves recurrence-free survival (HR 0.62,95% CI 0.49-0.79) 3
• These therapies have superseded interferon-alpha, which showed inconsistent results with considerable toxicity 1, 2

If SLNB Reveals Positive Nodes (Stage III)

• Additional adjuvant options include nivolumab (HR 0.72), pembrolizumab (HR 0.61), or dabrafenib + trametinib for BRAF V600 mutation-positive melanomas (HR 0.52) 3
• BRAF mutation testing becomes mandatory if nodal disease is discovered 2, 4
• Complete lymph node dissection may be considered for positive sentinel nodes, though this remains controversial 1

What NOT to Do - Critical Pitfalls

Outdated Therapies to Avoid

• Do not use adjuvant chemotherapy (dacarbazine, temozolomide) - no survival benefit demonstrated 1, 2
• Do not use adjuvant hormone therapy (progestogens) - no survival advantage 1, 2
• Do not use routine elective lymph node dissection without positive sentinel nodes 1
• Do not use adjuvant radiotherapy after complete excision with adequate margins 1, 2

Common Clinical Errors

• Failing to perform SLNB in ulcerated melanomas results in understaging and missed opportunities for appropriate adjuvant therapy 2
• Inadequate surgical margins lead to higher local recurrence rates, particularly critical in thick melanomas 2
• Not considering adjuvant immunotherapy in Stage IIC disease ignores level 1 evidence showing significant benefit 6, 3

Staging Workup Before Treatment

Imaging Requirements

• Imaging of nodal basin, chest/abdomen/pelvis is recommended for proper staging in melanomas >1 mm 1
• This is not low-risk melanoma (<1 mm), so comprehensive staging imaging is mandatory 1
• Physical examination must assess for tumor satellites, in-transit metastases, and regional/systemic metastases 1

Prognosis Context

• Stage IIC melanoma (>4 mm with ulceration, node-negative) has a 10-year melanoma-specific survival rate of 75% 3
• The presence of ulceration is a powerful adverse prognostic factor that upstages the tumor and mandates more aggressive management 2, 4
• Acral melanomas (including toe) may have different mutation profiles than cutaneous melanomas, though treatment algorithms remain similar 4