Treatment of Melanoma
Surgery is the cornerstone of melanoma treatment, with wide local excision margins determined by Breslow thickness, and systemic immunotherapy reserved for advanced disease. 1
Primary Localized Melanoma Treatment
Surgical Excision Margins
The surgical margins are determined by Breslow thickness and represent the standard of care 1:
- Melanoma in situ: 0.5 cm margin 1
- Breslow ≤1 mm: 1 cm margin 1
- Breslow 1-2 mm: 1-2 cm margin 1
- Breslow 2-4 mm: 2 cm margin 1
- Breslow >4 mm: 2-3 cm margin 1
Excision should extend to the muscle fascia or deeper 1. If tumor regression is noted on histology, use margins for the next thickness category up 1.
Sentinel Lymph Node Biopsy (SLNB)
SLNB is recommended for melanomas with Breslow thickness >1 mm 1. It may also be considered for melanomas >0.75 mm with additional risk factors such as ulceration or elevated mitotic rate 2. This should only be performed by experienced teams in specialized centers 1.
Adjuvant Therapy for Localized Disease
There is no standard adjuvant therapy for high-risk localized melanoma 1. High-dose interferon-alpha prolongs disease-free survival but not overall survival, and this benefit must be weighed against significant toxicity 1. Adjuvant chemotherapy and hormone therapy have not proven beneficial 1.
Radiotherapy is not indicated for operable melanoma 1, but should be considered when re-excision is not feasible (e.g., head and neck melanoma with inadequate margins) 1.
Regional Metastatic Disease (Stage III)
Lymph Node Management
Complete surgical resection of positive regional lymph nodes is mandatory for all patients who can tolerate surgery 1. The extent of lymphadenectomy should be determined by the multidisciplinary team, though no consensus exists on optimal extent 1.
Routine prophylactic lymph node dissection after excision of isolated cutaneous melanoma is not recommended due to significant morbidity (10-15% early complications, 6-15% late lymphedema in lower limbs) without proven survival benefit 1.
In-Transit Metastases
Surgical excision is the standard treatment for in-transit metastases 1. For numerous metastases or inoperable limb tumors, isolated limb perfusion with melphalan ± tumor necrosis factor may be considered, but only by specialized teams 1.
Adjuvant Therapy After Complete Resection
Adjuvant interferon-alpha is an option but cannot be routinely recommended due to inconsistent results showing possible benefit only in disease-free survival, not overall survival, with considerable toxicity 1. Patients must be strictly selected and closely monitored 1.
Adjuvant Treatment for Completely Resected Melanoma
Nivolumab (OPDIVO) is FDA-approved for adjuvant treatment of adult and pediatric patients 12 years and older with completely resected Stage IIB, IIC, III, or IV melanoma 3. This represents a significant advance over older interferon-based regimens.
Metastatic Disease (Stage IV)
First-Line Systemic Therapy
Nivolumab, as a single agent or in combination with ipilimumab, is FDA-approved for unresectable or metastatic melanoma in adults and pediatric patients 12 years and older 3. This immunotherapy approach has dramatically improved outcomes, with 5-year survival rates for stage IV disease increasing from 16% (pre-immunotherapy era) to 35% 4.
Molecular testing is mandatory for stage III or IV disease, including BRAF mutations and, if BRAF-negative, testing for NRAS and c-kit mutations 2.
Alternative Systemic Options
When immunotherapy is not appropriate, palliative chemotherapy with single agents (dacarbazine, vindesine, or temozolomide) may be given to patients with preserved performance status 1. Combination chemotherapy or chemo-immunotherapy has not been consistently superior to dacarbazine alone 1.
There is no proof that systemic treatment results in significant prolongation of survival in metastatic disease 1, though newer immunotherapies have changed this landscape considerably 3, 4.
Surgical Resection of Metastases
Surgical excision may be considered for slowly developing single metastases or in-transit metastases 1. Therapy should be adapted according to number of lesions, rate of disease progression, and patient performance status 1.
Special Considerations
Lentigo Maligna (Melanoma in Situ)
Standard treatment is surgical excision with 0.5 cm margin 1. If complete excision is impossible or contraindicated, options include radiotherapy, CO2 laser, or cryotherapy 1.
Local Recurrence
Surgical excision is the standard treatment for isolated local recurrence 1.
Common Pitfalls to Avoid
- Do not perform routine prophylactic lymph node dissection without sentinel node positivity, as morbidity is significant without proven survival benefit 1
- Do not use narrow excision margins to avoid local recurrence risk 1
- Do not delay molecular testing in advanced disease, as targeted therapies depend on mutation status 2
- Do not use adjuvant radiotherapy after complete nodal clearance, as it has not shown benefit 1
- Ensure adequate Breslow depth measurement by avoiding superficial shave biopsies; use deep scoop shave, saucerization, punch, or full-thickness excision 4
Follow-Up
Surveillance is indicated throughout life for all melanoma patients 1. Follow-up is based primarily on clinical examination and patient self-surveillance 1. Routine blood tests or imaging are not indicated in the absence of clinical signs or symptoms 1.
For melanomas with Breslow >1.5 mm or with histological regression: every 3 months for 4 years, every 6 months for years 5-10, then annually for life 1. For thinner melanomas (≤1.5 mm): every 3 months for 2 years, then every 6-12 months 1.
Patients should be instructed on lifelong sun protection, avoidance of UV exposure, and regular self-examination of skin and lymph nodes 1.