What is the oncological treatment for a patient with ulcerated nodular melanoma?

Oncological Medical Treatment for Ulcerated Nodular Melanoma

Primary Treatment: Surgery First

The standard treatment for ulcerated nodular melanoma is surgical excision with appropriate margins based on Breslow thickness, followed by sentinel lymph node biopsy given the presence of ulceration, and then consideration of adjuvant systemic therapy based on final staging. 1, 2, 3

Surgical Management Algorithm

Wide Local Excision Margins

• 1 cm margin for melanomas ≤2 mm Breslow thickness 1, 2
• 2 cm margin for melanomas >2 mm Breslow thickness 1, 2
• Nodular melanomas are typically thicker at presentation, so 2 cm margins are commonly required 3

Sentinel Lymph Node Biopsy (SLNB)

• Mandatory for all ulcerated melanomas regardless of thickness 1, 3
• Ulceration is an independent indication for SLNB even in thin melanomas 1
• Should only be performed by experienced surgical teams 1
• If positive, complete lymph node dissection has historically been performed, though recent data show no survival benefit from immediate completion dissection 4

Adjuvant Systemic Therapy Based on Final Stage

Stage IIB-IIC (Thick Primary, No Nodal Disease)

Anti-PD-1 immunotherapy is recommended as adjuvant treatment 3:

• Pembrolizumab 200 mg IV every 3 weeks for up to 1 year demonstrates improved recurrence-free survival (HR 0.65) and distant metastasis-free survival (HR 0.64) 5, 3
• Nivolumab also shows benefit with HR 0.42 for recurrence or death 3
• These agents significantly reduce recurrence risk compared to observation alone 3

Stage III (Regional Nodal Involvement)

Multiple effective adjuvant options exist 1, 3:

• Nivolumab (HR 0.72 for recurrence) 3
• Pembrolizumab (HR 0.61 for recurrence) 5, 3
• Dabrafenib + trametinib (HR 0.52 for recurrence) for BRAF V600 mutation-positive melanomas 3

The choice between anti-PD-1 therapy and BRAF/MEK inhibitors depends on BRAF mutation status and patient factors 1, 3.

Stage IV (Distant Metastatic Disease)

First-line treatment is dual checkpoint blockade 3:

• Ipilimumab (anti-CTLA-4) plus nivolumab (anti-PD-1) is the standard first-line therapy 1, 3
• This combination achieves 43% 10-year overall survival in metastatic disease 3
• BRAF mutation testing is mandatory before treatment selection 1
• Vemurafenib or other BRAF inhibitors (combined with MEK inhibitors) are options for BRAF V600 mutation-positive patients 1

Historical Context and Outdated Approaches

What NOT to Do

• Do not use adjuvant chemotherapy (dacarbazine, temozolomide) as standard treatment—these have shown no survival benefit in the adjuvant setting 1
• Do not use adjuvant hormone therapy (progestogens)—no survival advantage demonstrated 1
• Interferon-alpha showed inconsistent results in older trials and has considerable toxicity; it has been superseded by anti-PD-1 therapy 1
• Routine elective lymph node dissection is not recommended without positive sentinel nodes 1, 2

Critical Considerations for Ulcerated Nodular Melanoma

Why Ulceration Matters

• Ulceration is a powerful adverse prognostic factor that upstages the tumor 1, 3
• It mandates SLNB regardless of thickness 1
• It identifies patients who benefit most from adjuvant immunotherapy 1

Nodular Subtype Specifics

• Nodular melanoma represents approximately 5% of cases but is more aggressive 3
• These tumors grow vertically rather than radially, leading to greater thickness at diagnosis 3
• Earlier metastatic potential requires aggressive staging and treatment 3

Common Pitfalls to Avoid

• Inadequate surgical margins lead to higher local recurrence rates, particularly critical in thick melanomas 2
• Failing to perform SLNB in ulcerated melanomas results in understaging and missed opportunities for appropriate adjuvant therapy 1
• Delaying adjuvant immunotherapy in eligible patients (stage IIB-III) reduces the opportunity for improved recurrence-free survival 3
• Not testing for BRAF mutations in advanced disease limits treatment options 1
• Using outdated chemotherapy regimens when modern immunotherapy is available and superior 1, 3

Radiotherapy Role

• No role for adjuvant radiotherapy after complete excision with adequate margins 1, 6
• Consider radiotherapy only for incomplete nodal clearance (fixed nodes, extensive invasion, capsular disruption) 1, 6
• Palliative radiotherapy is appropriate for symptomatic brain or bone metastases in stage IV disease 1, 6