Currently there is no standard systemic adjuvant therapy for stage 3 melanoma. Chemotherapy has shown no evidence of benefit and despite high-dose interferon showing a small survival benefit in one study,14 it has not become standard in the UK. Attention has also focused on local adjuvant therapy, using radiotherapy. It is well documented that melanoma cells are radiosensitive if adequate total doses of radiation are used.15 Several studies have been conducted using radiotherapy in the adjuvant setting, but almost all are retrospective. The most convincing data for its use are in patients with intermediate thickness tumours of the head and neck, with or without regional nodal spread.
One study16 showed that in clinically node negative patients at high risk of nodal metastases, or following therapeutic nodal dissection, adjuvant radiotherapy may have a part to play in locoregional control. These factors have consistently been found to correlate with a high risk of relapse and a theoretical benefit of adjuvant radiotherapy in other nodal sites.13 There is no consensus in the UK about adjuvant radiotherapy after elective nodal dissection, but most radiation oncologists would assess each case on an individual basis, taking into consideration the risks as outlined. Complications of nodal radiotherapy are oedema, skin desquamation, fibrosis and mucositis.
Local recurrence and metastatic disease
Surgery is the treatment of choice for patients with single/operable local recurrences, and in transit or regional metastases. Other simple options for extensive but superficial disease are cryotherapy, diathermy curettage, laser, radiofrequency ablation, or direct cytotoxic drug injection into tumour nodules. For larger and deeply placed lesions, radiotherapy can be used.
For a small number of patients, the disease is too advanced or widespread within the limb to be treated by these methods; there may be a role for isolated regional chemotherapy, a technique known as isolated limb perfusion. This is not used regularly because only a small number of patients have disease in a suitable location. The rationale is to deliver high cytotoxic drug concentrations to the tumour without producing serious systemic side-effects.17 Early studies produced impressive results, with overall response rates of about 80 per cent and complete response rates of 30-50 per cent.
Another option for multiple cutaneous metastases, too numerous, too large or recurring too rapidly for multiple local excisions, is carbon dioxide laser ablation. A study in the UK found 1 per cent local recurrence rates after a median follow-up of eight months. Patients reported little or no pain after the operation and required only simple dressings. Wounds were healed in two to six weeks, with good cosmetic results.18
Metastatic melanoma remains one of the most difficult malignancies to treat. Several chemotherapy agents have been tried, but results are disappointing.19 No chemotherapeutic agent has shown significant improvement in survival rates. Dacarbazine remains the most active single agent, with a response rate of 20 per cent and a median duration of response of five to six months.20 A combination of active drugs has resulted in higher response rates, but these have not prolonged remission. The combination of dacarbazine and cisplatin increases response rates to 25 per cent,20 but is associated with increased toxicity, so is reserved for fitter patients.
Radiotherapy has a definite role in the palliation of MM. As in other cancers, it offers local treatment with fewer side-effects than systemic chemotherapy and particularly in melanoma, may have a higher response rate.21
Management of CNS involvement
The CNS is a known site of metastases from MM, with incidence of 10-40 per cent in clinical studies and higher in autopsy series.22 The prognosis for MM patients with cerebral metastases is poor. Median survival is nine to 20 weeks.22,23
Whole brain radiotherapy (see Figure 1) has been the standard of care for such patients,24 especially those with multiple metastases. However, surgery should be considered for single brain metastasis in patients with controlled (stable or responding) or controllable (expected to respond or remain stable) systemic disease.24 There is some evidence for use of temozolomide, alone25 or in combination with radiotherapy, in this situation.26 It has demonstrated 100 per cent oral bioavailability and extensive tissue distribution, including penetration of the blood-brain barrier and cerebrospinal fluid.
Another option is stereotactic radiotherapy. In this approach, high radiation doses are delivered to a limited target volume, with rapid fall-off outside the target.27 It is a highly effective local treatment of brain metastases,24 with advocates claiming that its survival data equal the data for surgery.28 The aim is to control growth of metastases or at least maintain quality of life.28 An upper limit of 3cm is usually applied, but two or three lesions can be treated simultaneously.
Follow-up guidelines for primary melanoma
In years one to three, patients should be followed up every three months, then six-monthly in years four to five. After this, they can be seen annually if they wish, or referred back under the care of their GP.6 A shared care approach is usual, alternating appointments with dermatologists or plastic surgeons. At every appointment, patients should undergo a thorough physical examination, looking for any new suspicious pigmented lesions. Particular attention should be paid to the site of the primary lesion, its surrounding skin and palpation of the lymph nodes for lymphadenopathy.6
All suspicious lesions should be referred to the dermatology team without delay. Any palpable lymph nodes should be referred to the surgical team for fine needle aspiration and consideration of lymph node dissection. CT and bone scans, X-rays, ultrasounds, FBC, RLB, LDH and other examinations are carried out when indicated. Patient education is an integral part of management. Patients should be advised about self-examination and the importance of safe sun behaviour.29
|Dr. Sarah Gwynne is a specialist registrar in clinical oncology at the Velindre Cancer Centre, Cardiff; Catherine Morgans is a skin oncology nurse for Cancer Care Cymru. Competing interests: None declared|
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