Elective Radiation Therapy to Regional Nodes
In addition to its role as definitive or adjuvant therapy, radiation treatment may be used electively (prophylactically) to treat suspected nodal disease, which is subclinical, particularly at sites such as the head and neck region where the draining node field is usually in close proximity to the primary tumour. Furthermore, this may obviate the need for SLNB.
In 2012, a French randomized trial of elective prophylactic regional radiotherapy vs. observation in patients with stage 1 MCC was published. All patients received wide local excision (the trial mandated at least 1·5 cm) followed by irradiation of the tumour bed; those randomized to the intervention arm also received radiation treatment to the regional nodes. This trial did not complete accrual but it remains distinguished by the fact that it is the only randomized trial performed in this disease to date. Eighty-three patients were accrued (of 210 originally proposed), and despite the small numbers, there was a statistically significant reduction in regional recurrence from 16·7% in the observation arm to 0% in the nodal radiotherapy arm. There was no difference in survival between the two trial arms. The authors state that the trial was interrupted prematurely because of a drop in recruitment, thought to be mainly due to the introduction of SLNB in the management of MCC.
In our experience, the role of SLNB in this disease remains controversial. In a series from the Melanoma Institute Australia (formerly the Sydney Melanoma Unit), eight patients had negative sentinel nodes. Despite the negative biopsy results, two of these patients received elective radiation treatment to the node field and did not recur; however, disease recurred in five of the six remaining patients within the node field. The sentinel node specimens were all re-reviewed by a pathologist subspecialized in cutaneous malignancies, but no metastases were detected even on review of both the routine haematoxylin and eosin-stained sections or on sections stained immunohistochemically for various MCC-associated antigens. Other series also report unacceptably high failure rates after negative SLNB in MCC ranging from 5% to 33%. In contrast, the failure rate for melanoma after a negative SLNB was only 2·7% in over 1000 patients treated at the Sydney Melanoma Unit. The expertise of the author surgeons dealing with MCC is not in doubt, suggesting that this entity behaves in a very different fashion from melanoma. Another recently published series from Westmead Hospital, Sydney has also reported a 20% false-negative rate for SLNB, reinforcing our concerns. Treating this disease using standard melanoma or nonmelanoma skin cancer paradigms is therefore inappropriate. However, the use of lymphoscintigraphy to identify the location of sentinel lymph nodes and draining node fields may be of value in rational radiotherapy field planning, particularly in areas with unpredictable lymphatic drainage, such as midline head and neck, or the torso.
Nevertheless, some groups have reported data that support the role of SLNB in this disease. For example, Gupta et al. published the Dana-Farber experience (61 patients) and a meta-analysis of the available literature (93 patients). In 39 of 122 (32%) patients initially presumed not to have nodal disease based on clinical examination, pathological involvement was discovered following SLNB. In patients with a negative SLNB, there was no significant difference in 3-year relapse-free survival rates for those who received (90%, n = 24) or did not receive (70%, n = 19) adjuvant nodal therapy. In addition, the use of SLNB has been recommended by Bichakjian and colleagues from Ann Arbor in a critical review with guidelines for the multidisciplinary management of this disease.