Where the melanoma is localised and thin (i.e. stage 1 disease), a local excision taking a centimetre around the lesion is almost always curative.
Where the disease is localised but the tumour is thicker than 1mm (i.e thick stage 1B or 2 disease) then a wider surgical excision is advised, taking 3 cm (sometimes 2 cm if at the better end of the depth prognostic scale or functional considerations make 3 cm unworkable) around the tumour – i.e. a wide margin of safety.
For stage 3 disease or patients who relapse in the regional nodes without evidence of relapse further afield, then elective surgical lymph node dissection is often recommended.
For patients with overt spread to further afield (e.g. lung or liver metastases or ‘satellite’ skin nodular metastatic disease) then systemic therapy (therapy that goes all around the body) is recommended.
Dacarbazine and cis-platinum chemotherapy have a response rate of around 30%+ if used together to treat stage 4 disease and other active drugs are vinca alkaloids and nitrosoureas. The optimum regime has yet to be found and none is capable of prolonged remissions reproducibly.
Some melanoma cells express oestrogen receptors and the anti-oestrogen drug tamoxifen (see breast cancer section) has been shown to have occasional activity in the disease.
Malignant melanoma has long been considered to be an ‘odd-ball’ cancer in that it can remain dormant for long periods and then progress rapidly and fatally, and some skin nodular disease can wax and wain. These observations had led many to speculate that there was some immune response mounted by the body in this type of cancer.
Recently, the immune stimulants alpha-interferon and interleukin-2 (a cytokine) have been used to good effect to produce remissions in stage 4 disease and even more recently some vaccination programmes have produced similar results – the vaccines derived from dead melanoma cells.In some of the studies, the combination of chemotherapy and immunotherapy has been used : ‘bio-chemotherapy’.
With the good responses of these immune therapies in advanced disease, it was not surprising that doctors moved the immunotherapies up into front line adjuvant therapy in stage 2 and 3 disease.
There are now data(see below), not convincing to all but enough to have changed current, standard practice in the USA, to support the routine use of adjuvant alpha interferon (in high dosage and after surgery) for such high risk patients without metastatic disease to distant organs.
Alpha interferon adjuvant therapy in stage 2 and 3 disease is still under investigation, but at present it is the only therapy that may reduce the risk of relapse in these patients.
Clinical data : The first study to demonstrate a benefit in favour of alpha-interferon adjuvant therapy, following surgery for higher risk, but localised, malignant melanoma, was the USA East Coast Oncology Group trial in the early 1990’s. In this study, published in 1996 (J Clin Oncol1996; 14:7-17), high dose interferon was administered for one year after surgical resection. It was a randomised trial where patients either received therapy with interferon or not. There was a survival benefit for those receiving therapy with interferon.
This study has subsequently been confirmed by some, but not all, other similar trials using adjuvant interferon.
