SUMMARY:
Surgery forms the mainstay of treatment for localised disease. All but Tis, and T1a,, tumours should have sentinel node biopsy, and if positive a regional node dissection
Radiotherapy is rarely used for primary treatment, except for lentigo maligna/lentigo maligna melanoma which is treated with superficial x-rays to 50 Gy in 20#.
Adjuvant radiotherapy to lymph node regions improves local control but not overall survival when patients have extranodal extension, 1-3+ lymph nodes involved or with large lymph nodes (>3-4 cm)
Palliative radiotherapy has a role to play in CNS metastases (30 Gy in 10#), bony metastases (30 Gy) or dermal metastases (36 Gy in 6#)
Systemic therapies are limited due to poor tuour response. Non-cytotoxic options may be more beneficial, including interleukin 2, ipilimumab or vemurafenib.
Melanoma management is dictated by the aggressiveness of the primary tumour, the presence of nodal metastases, or other distant metastases.
Local Treatment
Surgical excision of the primary melanoma is essential form diagnostic and curative purposes.
- Excision margins of at least 2 cm are preferred as they give the best rates of local control. Wider excisions have minimal evidence. For T1 lesions, a margin of 1 cm may be appropriate
Primary radiotherapy is only indicated for lentigo maligna in patients where surgical resection would lead to massive reconstruction or not be possible due to medical cormobidities. A similar dose to skin radiotherapy is used (eg. 50 in 20 fractions). Superficial delivery is usually sufficient as the tumour is non-invasive. This provides close to 100% control for lentigo maligna and 80-90% control for lentigo maligna melanoma.
All melanomas except stage IA (T1a) should undergo sentinel lymph node biopsy. If the sentinel node is positive, surgical resection of the lymph node region is indicated.
Adjuvant systemic therapy is typically considered for patients with stage IIB or IIC disease (T3b/T4a/T4b) as there is a high risk of relapse and death (30-80%). Inteferon alpha has been shown in large trials to improve disease free survival.
Regional Treatment
Nodal disease is the most common site of initial relapse or may be present at diagnosis. It is a hallmark of metastatic disease and treatment of nodal groups has rarely shown improvements in survival in randomised trials.
Surgical lymphadenectomy is the standard of care and provides local control in 80% of patients.
Adjuvant radiotherapy has been shown to be beneficial by the TROG 02.01 trial. This was given for patients with "high risk" of relapse. It reduces local recurrence by 50% (from 30% to 15%) similar in magnitude to breast DCIS. It has no impact on overall survival which is poor (50%). High risk features are:
- Numbers of nodes involved:
- 1 parotid node or cervical node
- 2 axillary nodes
- 3 inguinal nodes
- Size of involved nodes:
- 3 cm in parotid or neck
- 4 cm in axilla or inguinal region
- Extracapsular extension
The total dose is 48 Gy in 20 fractions.
Systemic Disease
Conventional cytotoxic therapy (dacarbazine) has disappointing results with low rates of response (~ 20%) and therefore other approaches have been explored:
- Interleukin-2 is only active in 15-20% of patients but in a small number may result in complete response and potential cure even with metastatic disease (about 2% of treated patients). Toxicity can be severe and includes cardiac and respiratory difficulties
- About 50% of melanomas contain a mutation in the V600 codon of BRAF, leading to overexpression of the MAPK pathway. This can be targeted with BRAF inhibitors (e.g. vemurafenib) which produce high rates of response. Unfortunately response only occurs while on medication, and even then is usually limited to 6 - 12 months.
- Ipilimumab is a CTLA4 targeting monoclonal antibody that causes an immune response against the tumour. It has a proven benefit in median survival but is associated with auto-immune complications.
Palliative Radiotherapy
Radiotherapy can provide good symptomatic relief at most metastatic sites:
- Bone or brain are effectively treated with 30 Gy in 10 fractions
- Dermal or nodal sites may be treated with 36 in 6 fractions (twice weekly) with good results
