Radiation therapy is not part of the traditional treatment approach to cutaneous melanoma. Aggressive surgical resection of both the primary site and regional nodal metastases has long been considered the only option for achieving long-term disease-free and overall survival. Many patients who present with melanoma have thin lesions (< 1 mm Breslow thickness) and are essentially cured with a wide local excision of the primary site. Patients with thicker melanomas and clinically negative regional nodal basins often undergo wide excision and sentinel node biopsy to identify occult nodal metastases. Those who have a sentinel lymph node positive for metastatic disease or clinically positive nodes undergo a therapeutic lymph node dissection to provide local control and possibly prevent distant metastatic disease. Recent articles such as the one by Ballo and Ang, however, highlight the in- creased role of external-beam radiation therapy in the treatment of malignant melanoma.
Role of Adjuvant Radiation Therapy
A recent paper from the Centre for Evidence-Based Medicine at the University of Oxford examined randomized clinical trials comparing narrow vs wide excision of primary cutaneous melanoma, which included more than 2000 patients.[1] These authors reported that the overall rate of local recurrences as the first relapse of melanoma was 0.01%, with no difference between the wide and narrow excision margins. For the majority of patients, wide excision with 1- or 2-cm margins (depending on the Breslow depth) provides excellent local control. Yet, as Ballo and Ang note, there are subgroups of patients whose melanomas possess features rendering them at higher risk for local recurrence. These patients include those with desmoplastic melanomas and thick melanomas (> 4 mm) with ulceration.
Investigators have reported that in a recent study, adjuvant radiation therapy decreased further recurrences after the resection of recurrent desmoplastic melanoma.[2] No data are available on the use of radiation after resection of thick, ulcerated melanomas. Close or positive resection margins as an indication for adjuvant radiation therapy should rarely occur in the treatment of primary melanoma, except possibly for lesions on the face.
Adjuvant radiation therapy is more well-established in the treatment of regional nodal metastases, especially for melanomas of the head and neck. There is strong evidence that extranodal extension is the most significant risk factor for regional recurrence and a clear indication for adjuvant radiation therapy. In a review from the John Wayne Cancer Institute of 196 patients with cervical nodal metastases treated with neck dissection, the 5-year regional recurrence rate was 31% and 13% for those with and without extranodal extension, respectively [3].
Ballo and Ang also recommend adjuvant radiation for cervical nodal disease, based on two published series[ 4,5] that showed an increased regional recurrence rate for cervical metastases compared to axillary or inguinal disease. The cervical region can be a more difficult area in which to perform a lymph node dissection because of the close proximity of neuro- vascular vital structures. It would be interesting to examine the total number of nodes obtained in basins where regional recurrence developed vs those where it did not, to determine whether regional recurrence is associated with an inadequate initial lymphadenectomy.
Future Horizons
This article also discusses the use of elective regional nodal radiation therapy in patients who are not candidates for systemic therapy or regional lymph node dissection. In this setting, radiation therapy assumes a role similar to that of elective lymph node dissection, which may be used to treat a clinically negative regional nodal basin. Elective lymph node dissection has been shown in a randomized trial conducted by the Intergroup Melanoma Surgical Program to make no difference in overall survival.[6] Table 5 in Dr.Ballo's article reports a weighted average risk of 21% and 33% for a positive sentinel node in patients with intermediate and thick melanomas, respectively. Therefore elective radiation therapy for patients with clinically negative regional nodes will subject 70% to 80% of patients to unnecessary therapy while exposing them to the potential morbidity of radiation therapy.
The use of sentinel node biopsy to stage a clinically negative regional nodal basin has revolutionized the care of patients with primary melanoma, allowing accurate staging with a minimally invasive procedure that most patients can tolerate. The combination of sentinel node biopsy with regional nodal irradiation for a positive sentinel node is an intriguing one. In this manner, only patients with histologically proven regional metastases are treated, and in patients with truncal melanomas, all the draining lymphatic basins are identified through lymphatic mapping using lymphoscintigraphy. Certainly before this approach can be adopted for clinical care, it needs to studied in a randomized trial comparing completion node dissection to regional nodal irradiation for a positive sentinel node.
Conclusions
The article by Ballo and Ang emphasizes the need to consider a multimodality approach to the treatment of primary and regionally metastatic cutaneous melanoma. Certainly the combination of surgery, radiation therapy, and chemotherapy has been shown to improve outcomes in the treatment of breast cancer and many gastrointestinal malignancies.
At this time, there is no proven efficacious systemic regimen for advanced melanoma, emphasizing the importance of thorough comprehensive treatment for primary melanoma to prevent regional or distant recurrences. Adjuvant radiation therapy for melanoma has a well-defined role in specific situations and presentations of melanoma. However, further prospective studies are necessary to fully define the potential benefit of radiation therapy in melanoma and how it should be implemented in relation to wide excision and sentinel node biopsy.
Financial Disclosure: The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.
