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Melanoma and Lymph Nodes: When to Choose Sentinel Lymph Node Biopsy
In 2016, over 75,000 patients will be diagnosed with melanoma in the United States. The vast majority of these patients (95%) will present with disease localized to the skin and lymph nodes. Although the prognosis for most of these patients is excellent, the presence of metastases in the regional lymph nodes dramatically impacts survival. Lymph node status is an important prognostic criteria and, as such, guides decisions for adjuvant systemic therapy.
Current clinical practice guidelines recommend that initial work-up for patients newly diagnosed with melanoma include a thorough history and physical exam, including a complete dermatologic exam. Given the prognostic importance of involved regional lymph nodes, specific attention should be paid to the regional lymph node basin. Suspicious findings should be evaluated with ultrasound, CT or PET/CT imaging, and subsequent biopsy performed if indicated.
Sentinel lymph node biopsy
For patients with clinically negative regional lymph nodes, further pathologic staging is often recommended. This can be accomplished using the minimally invasive approach of a sentinel lymph node (SLN) biopsy. Sentinel lymph nodes are the first lymph nodes (often one or two) to which melanoma would spread. To identify these nodes, a radioactive protein and often a blue dye are injected near the primary melanoma tumor. These substances are then taken up into the lymphatic channels and drain to the sentinel lymph nodes. The surgeon can identify these sentinel lymph nodes and remove them at the time of surgery for enhanced pathologic evaluation.
The Multicenter Selective Lymphadenectomy Trial-I was an international phase III trial that evaluated the SLN biopsy procedure. Patients with clinically negative lymph nodes were randomized to undergo SLN biopsy versus ongoing surveillance of the lymph nodes with surgery reserved for if metastatic disease became clinically evident. In this study, SLNs were successfully identified in 95% of patients. This study did not identify a survival advantage in association with receipt of a SLN biopsy. However, the trial determined that the SLN biopsy is a highly prognostic, with the 5-year overall survival for patients with negative SLNs 90% but only 72% for patients with SLNs involved with metastases. The SLN biopsy identifies a group of patients at increased risk of subsequent recurrence who may benefit from more intensive follow-up regimens or additional adjuvant systemic therapy.
One of the strongest predictors of having a positive SLN is tumor thickness, with additional adverse pathologic features such as ulceration and present of mitoses also contributing. The National Comprehensive Cancer Network (NCCN) guidelines recommend that a SLN biopsy be considered for patients whose primary melanoma is >1 mm in thickness; the likelihood of these patients having a positive SLN exceeds 5-8%. The NCCN guidelines also state that the SLN biopsy should be considered and discussed with patients whose melanomas are between 0.76 and 1.0 mm in thickness, especially in the presence of ulceration or mitoses. The guidelines currently recommend against the use of SLN biopsy in melanoma <0.75 mm in thickness given the low rate of nodal metastases in these patients.
The lack of survival benefit but strong association with prognosis should be considered when selecting patients to undergo a SLN biopsy. Although reported complications of the SLN biopsy are low, infection, seroma, and lymphedema do occur in 2-5% of patients. Additionally, patients with multiple comorbidities and a limited life expectancy will be less likely to benefit from the prognostic information obtained through the SLN biopsy. Considering the specific circumstances for each individual patient, including their risk of SLN metastases based on the characteristics of their primary melanomas, the likelihood of being recommended adjuvant systemic therapy, and the perceived importance to the patient of knowing their prognosis, are critical aspects of surgeon decision making when deciding whether to perform a SLN biopsy.
SLN biopsy is an accurate and low-morbidity technique of providing pathologic lymph node staging for patients with melanoma. The SLN biopsy provides important prognostic information and can be used to direct recommendations for more intensive follow-up or adjuvant systemic therapy. However, given the lack of a proven survival benefit, decisions whether or not to recommend a SLN biopsy should be personalized based on patients’ preferences and overall life expectancy.
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