Discussion

Current surgical management

of limb malignant melanoma

Lingam MK, McKay AJ

Department of Vascular Surgery

Gartnavel General Hospital - Great Western Road

Glasgow G12 OYN - Scotland - United Kingdom

The unpredictable natural history of malignant melanoma renders it unusual among human tumours. The tendency to arise from a benign lesion, its capacity to spread without regard for anatomical boundaries, its ability to lie dormant for many years and finally its tendency for spontaneous regression contribute to our lack of understanding of melanoma and our inability to deal with it more effectively.

The incidence of malignant melanoma is rising worldwide at a rate of 6% - 7% per year which is faster than any other cancer1. In Scotland (population of 5 million), 588 cases were registered in 1992, an increase from 507 in 1991. Approximately 50% of all melanomas occur on the extremities and a large percentage of these occur in women2. Multivariate analysis of prognostic variables has shown that the most important prognostic factors are pathological stage, ulceration, thickness and site.

Since Handley delivered his Hunterian lecture4 in 1907, the treatment of malignant melanoma has been almost exclusively surgical, and based on wide excision of the primary tumour with or without regional lymphadenectomy.

For many years wide excision margins were recommended to remove occult foci of melanoma cells which could lead to metastasis or local recurrence. Current practise is to excise the primary malignant melanoma with surgical margins that are based on tumour thickness and ulceration, as these factors correlate with the risk of local recurrence5,6. It is known that the incidence of local recurrence or metastasis from melanoma less than 0.76mm thick is not affected by the width of the excision margin7.

The World Health Organisation (WHO)8 randomised study of 612 patients in whom excision was randomised to 1 or 3 cm, demonstrated that a 1 cm margin was adequate for primary melanoma less than 1mm thick. The optimal excision margin for melanoma thicker than 1mm is still controversial9,10. Indeed, a further randomised study is presently being conducted on excision margins in the United Kingdom (Meirion Thomas, Royal Marsden Hospital, London).

Our current recommendations for surgical margins are as follows:

    Type                                  Margin

    In situ                              local excision

    <1mm thick                          1 cm

    1-3mm thick                           2 cm

    > 3mm                                 3 cm (if cosmetically possible)

The site of the primary lesion clearly has an important bearing on excision margins.

The surgical world still has considerable difficulty in knowing how to deal with lymph nodes which may not contain metastatic malignancy. Most would agree that involved lymph nodes should be removed, but what if nodes are not clinically involved and yet contain micrometastases? Such a situation is probably more common than has been hitherto realised and has important implications for the staging of disease and interpretation of therapeutic trials.

Those surgeons who advise immediate elective lymph node dissection in all patients with high risk malignant melanoma (Breslow 1.5 - 4.0mm) must accept that many patients will undergo an unnecessary operation which is associated with significant morbidity11.12. Others adopt a 'wait and see' policy and remove lymph nodes if and when they become clinically palpable13,14. Neither policy is ideal, but around the world enthuasium for elective lymph node dissection is waning15.

If a technique could be developed that would allow positive identification of the subgroup of patients with clinically occult nodal disease, it may well be that such patients would be most likely to benefit from lymphadenectomy. Lymphatic mapping first described by Morton16 and Cochran17 may be such a technique.

Intraoperative lymphatic mapping has been developed on the assumption that metastases embolise via lymphatic channels to the regional lymph nodes. The technique is based on identifying the first or sentinel lymph node (the draining lymph node nearest the primary melanoma) and examining it for micrometastases. The method depends on using a dye to stain this sentinel node.

Patent blue dye is injected around the site of the primary melanoma, the regional lymphatic basin is explored and the blue lymphatic channels are followed to the first stained blue node. We have performed this technique in 40 patients with clinically stage I disease. Sentinel nodes were identified in all patients and nine nodes were found to contain micrometastases.

Our pilot study revealed that it was not possible to predict the status of the sentinel node from the Breslow thickness of the primary tumour. This is perhaps surprising as the proponents of elective lymphadenectomy claim that the risk of developing regional node disease increases with the thickness of the primary melanoma and propose that elective lymph node dissection is most beneficial in those patients with intermediate thickness tumour (1.5-4.0mm)18.

However, tumour ulceration did appear to be significant in the prediction of sentinel node status. Seven of the nine patients with positive sentinel nodes had ulceration in the primary tumour while only one of the thirty-one patients with negative sentinel nodes had ulceration in the primary tumour.

Our initial experience of this technique suggests that it is sensitive and easy to master. It may allow us to reserve lymphadenectomy for patients in whom metastases are positively identified. A multicentre study is currently in progress on the role of lymphatic mapping in malignant melanoma. The WHO are also proposing a multicentre study of the technique. The exact role of intraoperative lymphatic mapping must await the outcome of these studies but our initial experience does show that it is practical and allows detection of clinically unsuspected disease.

Since 1984, we have been using isolated limb perfusion in the management of limb malignant melanoma. In a study of 120 patients with lesions greater than 1.5mm (mean thickness 3.1mm) we have been unable to show survival benefits for adjuvant isolated limb perfusion using melphalan and mild hyperthermia (<40 C). Though there is a trend in favour of the isolated limb perfusion group both in terms of survival and time to first recurrence, this does not reach statistical significance. This finding has been supported by a prospective study of isolated limb perfusion being conducted by the members of the EORTC melanoma subgroup. At the present time it is not possible to recommend routine adjuvant isolated limb perfusion using melphalan for patients with limb lesions more than 1.5mm.

We continue to use isolated limb perfusion for patients with recurrent melanoma of the extremities. In more than 180 patients, we are able to achieve a complete response of 80% and a partial response of 19%. These results are comparable with those being achieved in other centres19,20.

When isolated limb perfusion is not possible, or has failed to achieve disease control, the option for disease control includes isolated limb perfusion with melphalan and tumour necrosis factor, or laser ablation. The addition of tumour necrosis factor to the perfusion circuit has produced encouraging results, though the morbidity of the procedure rises21. Our own experience of laser ablation is limited to 19 patients but we are convinced that it is a useful means of achieving local control and has the great benefit of being a relatively minor procedure which can be readily repeated22.

Despite the vast increase in our knowledge of melanoma in all its facets, it seems extraordinary that the prognosis for an individual patient given appropriate surgery, has not changed since 1907. If improvement of disease control and prognosis is to be achieved, then targeting and destroying subclinical melanoma metastases must be the way forward. We have

shown that in animal studies the use of targeted radiotherapy is effective in killing melanoma cells. Other investigators have reported the value of melanoma cell vaccincs24.

At present, sensible local excision and more accurate staging is possible. Local disease control is usually achievable. Adequate treatment for disseminated disease remains elusive.

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