Some aspects of radiotherapy for melanoma
The incidence of malignant melanoma is rising among white adults in the Western world. Surgical excision is the treatment of choice for the primary lesion, local recurrence and nodal metastases. However, two papers in this issue look at the use of other treatment modalities. We comment specifically on the use of radiotherapy in these articles.
Fuhrmann et al. have looked at the role of adjuvant radiotherapy following resection of regional lymph node metastases.1 Adjuvant treatment in melanoma is very much an unresolved area. There is presently much interest in systemic adjuvant therapies, as the majority of patients who die do so with disseminated disease. The current MRC trial AIM HIGH is investigating the role of adjuvant interferon-α following the improved survival rates demonstrated by Kirkwood et al. in the ECOG 1684 study.2 However, there is no large randomized controlled trial (RCT) evidence defining the role of postoperative radiotherapy and there are no ongoing studies.
The loco-regional lymph nodes are the most common metastatic site in melanoma. Four prospective RCTs (WHO 1, Mayo, WHO 14, Intergroup) looked at the role of elective lymph node dissection following excision of the primary lesion and failed to show a significant difference in overall survival. Current policy is careful observation, but the role of sentinel node biopsy is being extensively explored.
The role of postoperative radiotherapy at nodal recurrence is not clearly defined, with most recommendations based on retrospective, single-institution studies. Fuhrmann et al. demonstrate the significantly increased risk of distressing complications such as lymphoedema, with little apparent benefit in terms of either overall survival, disease-free survival and local control. There may be several reasons why they failed to demonstrate a survival benefit including a small study number and pairs not matched for depth of invasion, thickness and site of the primary lesion (the most important prognostic factors for survival in melanoma) and particularly, the use of short distance cobalt irradiation to the node sites, a beam which has a field of influence of approximately 3 cm. Very few patients were treated on modern supervoltage linear accelerators. In a nonrandomized setting one has to ask why some patients received radiotherapy and some did not; usually because of some unidentified poor prognostic factor, or maybe the fact that dealing with a systemic disease needs systemic treatment. The majority of patients died with metastatic disease, free of recurrence in the regional lymph node area.
The authors cannot recommend adjuvant radiotherapy in this setting and suggest a multicentre prospective RCT is needed. However, this may not be feasible as a single treatment option, given the ongoing interest in and potential success of systemic therapy. They clearly show that nodal relapse is a marker of systemic disease, but suggest radiotherapy where isolated nodes and recurrences have occurred. Radiotherapy continues to be an option to control fungating and inoperable nodes where quality of life is the most important issue.
Mahendran et al.3 have carried out a postal questionnaire survey to assess dermatological management of lentigo maligna, the in situ phase of lentigo maligna melanoma. Within all age groups surgery was the preferred treatment with high established cure rates, but there was increasing use of cryotherapy, radiotherapy and observation with age. In fact, in the cited series there seemed little difference between the results with the differing modalities used to treat lentigo maligna. They have clearly demonstrated the need for a standard treatment algorithm, which they propose, with the finding that most UK dermatologists only see a few cases of lentigo maligna each year.
Retrospective series have concluded that conventional fractionated radiotherapy with superficial or Grenz rays is a cosmetically acceptable, effective and simple outpatient treatment.4 A recent study has documented excellent results in lentigo maligna melanoma. However, radiotherapy is not a standard practice due to the lack of formal histology; pretreatment biopsies provide no information on margins and possibly failing to detect microinvasive melanoma.5 However, lentigo maligna is seen predominantly in an elderly population with a higher percentage of patients declining or unsuitable for surgery this option should then be considered.
