What are the treatment options for malignant melanoma?

Treatment Options for Malignant Melanoma

The treatment of malignant melanoma requires a stage-specific approach, with surgical excision being the cornerstone of therapy for localized disease, while advanced melanoma may require immunotherapy agents such as pembrolizumab or nivolumab. 1

Diagnosis and Staging

Before initiating treatment, proper diagnosis and staging are essential:

• Diagnosis should be based on full thickness excisional biopsy with 2mm margins of normal skin 1
• Histology report should include:
  • Breslow thickness (mm)
  • Clark invasion level (I-V)
  • Surgical margin clearance
  • Presence of ulceration
  • Presence and extent of regression 1

Staging workup includes:

• Physical examination focusing on tumor satellites, in-transit metastases, and regional lymph nodes
• Basic laboratory tests (blood count, LDH, alkaline phosphatase)
• Imaging based on tumor thickness:
  • Chest X-ray for all patients
  • Sonography of abdomen and regional lymph nodes for melanomas >1mm or with suspicious findings
  • Further imaging as clinically indicated 1

Treatment by Stage

1. Localized Disease

Surgical Management:

• Wide excision with specific margins based on tumor thickness:
  • In situ melanoma: 0.5 cm margin
  • 1-2 mm thick: 1 cm margin

  • 2 mm thick: 2-3 cm margin 1, 2

• Modifications may be needed for functional preservation in anatomically sensitive areas (fingers, toes, ears) 1

Lymph Node Assessment:

• Sentinel lymph node biopsy (SLNB) should be performed for:
  • Melanomas >1 mm thick
  • Thinner melanomas with high-risk features (ulceration, high mitotic rate)
• SLNB should be performed only by skilled teams in experienced centers 1, 2
• Complete lymph node dissection if sentinel node is positive 1

Adjuvant Therapy:

• No standard adjuvant therapy for high-risk melanoma
• High-dose interferon may provide disease-free survival benefit but not overall survival benefit
• Toxicity must be weighed against potential benefits 1
• Adjuvant chemotherapies and hormone therapies have not proven beneficial 1

2. Locoregional Metastatic Disease

• Complete surgical resection of positive regional lymph nodes for all patients who can tolerate surgery 1
• For in-transit metastases or inoperable primary tumors of limbs:
  • Isolated limb perfusion with melphalan and tumor necrosis factor
  • Radiation therapy as an alternative 1
• No standard adjuvant therapy after complete resection 1

3. Systemic Metastatic Disease

• Immunotherapy with PD-1 inhibitors:

  • Pembrolizumab for unresectable or metastatic melanoma 3
  • Nivolumab as single agent or in combination with ipilimumab 4

• Chemotherapy options (less effective than immunotherapy):

  • Single-agent chemotherapy (dacarbazine, temozolomide, vindesine) for patients with preserved performance status 1
  • No proven survival benefit with combination chemotherapy over single agents 1

• Other options:

  • Surgery for isolated metastases in selected patients with good performance status 1
  • Palliative radiotherapy for symptomatic brain or bone metastases 1
  • Best supportive care for patients with poor performance status 1

Follow-up Recommendations

• Follow-up duration:

  • 5 years for localized melanoma ≤1.5 mm thick
  • 10 years for thicker melanomas 1

• Follow-up schedule:

  • Every 3 months for first 2 years
  • Every 6-12 months thereafter 1

• Patient education:

  • Avoid sunburns and unprotected UV exposure
  • Perform regular self-examination of skin and peripheral lymph nodes 1

Special Considerations

• Subungual and auricular melanomas can be treated with less radical procedures than amputation 5
• Melanomas diagnosed during pregnancy can be treated with wide local excision under local anesthesia, with SLNB delayed until after delivery 5
• Desmoplastic melanoma management is controversial regarding SLNB indications and postoperative radiation therapy 5

Common Pitfalls

1. Inadequate surgical margins: Ensure appropriate margins based on tumor thickness to reduce recurrence risk 1, 2

2. Overuse of imaging: PET scanning is not useful for initial staging of clinically localized melanoma 1, 6

3. Delayed diagnosis: Early detection significantly reduces morbidity and mortality; suspicious lesions should be promptly biopsied 7, 8

4. Inappropriate use of adjuvant therapy: No proven benefit of adjuvant chemotherapy or hormone therapy; interferon has limited benefit with significant toxicity 1

5. Inadequate follow-up: Regular monitoring is essential for early detection of recurrence, especially in the first 2-3 years when risk is highest 1