What are the treatment options for managing melanoma?

Management of Melanoma: A Comprehensive Approach

The optimal management of melanoma requires a multidisciplinary team approach with treatment strategies determined by disease stage, with surgical excision being the cornerstone of treatment for early-stage disease and immunotherapy/targeted therapy for advanced disease. 1

Diagnosis and Initial Assessment

• Complete clinical evaluation including whole-body imaging and serum LDH analysis for advanced disease
• Genetic mutation analysis (particularly BRAF status) for metastatic disease
• Central nervous system (CNS) assessment for advanced disease
• Evaluation by a qualified surgical oncologist for possible metastasectomy 1

Treatment by Stage

Melanoma In Situ (Stage 0)

• Surgical excision with 0.5-1.0 cm margins is the standard first-line treatment 2
• Depth of excision should extend to but not include the fascia
• For lentigo maligna type (especially on face, ears, or scalp):
  • Mohs micrographic surgery or staged excision with permanent sections
  • Wider margins may be required due to subclinical extension 2
• Alternative treatments when surgery is contraindicated:
  • Radiotherapy (approximately 5% local failure rate)
  • Topical imiquimod 5% cream (75-90% complete clearance rate)
  • CO2 laser or cryotherapy in select cases 2

Early-Stage Melanoma (Stage I-II)

• Wide local excision with margins based on Breslow thickness:
  • In situ: 0.5-1.0 cm margins
  • Thin melanomas: 1 cm margins
  • Thicker melanomas: 1-2 cm margins 1
• Sentinel lymph node biopsy (SLNB) should be considered for:
  • All patients with primary melanoma stage IB and higher 1
• No adjuvant therapy is standard for completely resected stage I-IIA disease 1

Regional Disease (Stage III)

• Complete lymph node dissection for clinically positive nodes 1
• Adjuvant therapy options:
  • Pembrolizumab or nivolumab for completely resected stage IIB, IIC, or III melanoma 3, 4
  • Interferon-α may be considered but has significant toxicity and limited benefit 1

Metastatic Disease (Stage IV)

• Surgical approach:

  • If complete resection of all metastatic disease is possible, metastasectomy should be considered as first-line treatment 1
  • Particularly beneficial for solitary metastases 1

• For unresectable disease, treatment approach based on:

  • BRAF mutation status
  • Performance status
  • CNS disease presence 1

• For BRAF-mutated melanoma:

  • Good performance status, no CNS disease: Immunotherapy first (IL-2 if eligible), followed by BRAF inhibitor upon progression
  • Poor performance status or uncontrolled CNS disease: BRAF inhibitor (vemurafenib, dabrafenib) as first-line therapy 1

• Immunotherapy options:

  • Anti-PD-1 antibodies (pembrolizumab, nivolumab)
  • Combination ipilimumab (anti-CTLA-4) plus nivolumab
  • High-dose IL-2 in selected patients 1, 3, 4

• Conventional palliative chemotherapy (dacarbazine) when other options exhausted 1

Follow-up and Surveillance

• Clinical examination is the standard for surveillance 1
• Self-surveillance should be encouraged through patient education
• Lifelong follow-up recommended:
  • Melanoma in situ: Annual follow-up
  • Invasive melanoma: Every 3 months for 4 years, every 6 months for years 5-10, then annually 1
• No routine blood tests or imaging in the absence of clinical signs or symptoms 1

Common Pitfalls and Caveats

1. Delayed referral: Patients with primary melanoma stage IB and higher should be promptly referred to a Skin Cancer Multidisciplinary Team 1

2. Inadequate surgical margins: Ensure complete histological clearance, particularly for lentigo maligna where subclinical extension is common 2

3. Missed timing for adjuvant therapy: Most clinical trials require entry within 8 weeks of completion of surgery 1

4. Suboptimal sequencing of therapies: For BRAF-mutated melanoma, consider immunotherapy first in patients with good performance status due to the potential for durable responses 1

5. Overlooking metastasectomy: Surgical resection of oligometastatic disease can provide long-term disease-free survival in selected patients 1