Melanoma Management: Options for Newly Diagnosed Patients
The role of sentinel lymph node biopsy and options for treatment after initial surgery are areas that are of particular interest to patients who are newly diagnosed with melanoma.
Melanoma remains the deadliest form of skin cancer. Its rapidly increasing incidence over the last several decades, together with our aging population, will result in dramatic increases in the number of newly diagnosed patients.
Significant advances in the assessment and treatment of patients with melanoma over the last several years, however, now allow more individualized treatment, which is both more effective and less toxic than earlier alternatives.
Two areas that are of particular interest to patients who are newly diagnosed with melanoma are the role of sentinel lymph node biopsy in their care, and options for treatment after that initial surgery. Both areas have seen rapid advancement in the modern era and have been evaluated in clinical trials, data from which recently have been reported (Table 1).
Regional Lymph Node Management
In most cases in which melanoma metastasizes, the site of initial metastasis is the regional nodal basin. This clinical finding was noted more than a century ago and led to proposals for immediate removal of all regional lymph nodes at the time of initial treatment for every melanoma diagnosis. This “elective lymph node dissection,” however, was accompanied by a significant risk of morbidity, and in most cases, all of the lymph nodes removed in the operation were normal (Figure 1A). Randomized trials evaluating elective node dissection did not show an unequivocal survival benefit, though trends toward benefit were fairly consistent, with significant survival improvements in several subgroup analyses.
While the elective-node debate raged on, Morton and colleagues altered the treatment landscape through the development of lymphatic mapping and sentinel lymph node biopsy.1 This enabled regional staging, which was actually more accurate than the older, larger operation and spared most patients the morbidity of complete dissection. (Figure 1B). With a negative sentinel node, patients could have their regional nodes safely observed. At the time, those with sentinel node metastases went on to completion dissection. The old debate was completely reframed as a result.
The technique was subjected to evaluation in large, multicenter clinical trials. The long-term results of one of these trials, the first Multicenter Selective Lymphadenectomy Trial (MSLT-I) were reported in 2014 and clarified the utility of the procedure.1 First, MSLT-I confirmed that the pathologic status of the sentinel node was the most important prognostic variable. In fact, the staging accuracy of sentinel node biopsy was markedly better than that of elective lymph node dissection, because pathologists could concentrate their examination on a small number of nodes, making evaluations such as immunohistochemistry possible. This prognostic validation followed numerous prior retrospective series and other prospective clinical trial data.
MSLT-I also confirmed that the procedure was generally well tolerated with much less toxicity than compete dissection. Even for those patients who underwent full dissection, MSLT-I showed that proceeding with that surgery for clinically occult disease (detected by sentinel node biopsy) had a lower risk for the most feared complication, lymphedema, than those who underwent dissection for a clinically detected recurrence. Finally, for patients with intermediate thickness melanomas, early removal of nodal metastases was associated with a marked reduction in the risk of dying of melanoma compared with later removal at the time of clinical recurrence.
Based on these and other data, the procedure is now a accepted as part of standard melanoma management for patients with intermediate-thickness and thick melanomas. Uncertainty remains regarding which patients with thin melanoma should be considered for the procedure, due to their low risk of metastasis for those patients.
The most recent guidelines from the American Society of Clinical Oncology, the Society of Surgical Oncology, and the National Comprehensive Cancer Network suggest that for patients with melanomas with tumor thickness from 0.8 to 1 mm, the procedure should be considered as an option.2
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