Melanoma recurred in 16% of patients after negative SLNB

Vernon K. Sondak, MD

Sentinel lymph node biopsy is widely used for the staging of clinically node-negative cutaneous melanoma, and recent evidence-based guidelines issued jointly by ASCO and the Society of Surgical Oncology indicate that it should be recommended or considered for patients with intermediate and thick melanomas (Breslow thickness ≥1 mm) and selected patients with thin melanomas <1 mm.

Overall, about 15% to 20% of patients have a positive sentinel node, and a large randomized trial showed that melanoma patients with a positive sentinel node are about three times more likely to relapse and die of melanoma compared with those with a negative sentinel node. Because at least 80% of patients who undergo the sentinel node biopsy procedure have a negative sentinel node, it is very important for clinicians and patients alike to understand the implications of a negative biopsy result. The study by Jones and colleagues adds to a growing body of literature on this subject, and the results are quite consistent with other similar studies.

As their study clearly shows, a negative sentinel node biopsy result does not guarantee that a patient’s melanoma will not recur. Jones and colleagues found that 4% of their patients eventually developed recurrent melanoma within other lymph nodes in the sentinel node-negative basin, a finding very consistent with other reports. Looked at the other way, 96% of patients whose sentinel nodes were negative had no evidence of nodal recurrence, further substantiating the conclusion that sentinel node biopsy provides accurate staging with a low rate of nodal failures. However, this 4% regional node basin failure rate can also be looked at another way: The sentinel node biopsy procedure only identified 80% of all patients with a positive node, for a false-negative rate of approximately 20%.

Older males and patients with head and neck primary melanomas are at highest risk for a false-negative biopsy. New techniques such as SPECT/CT lymphoscintigraphy may help lower false-negative rates, especially in the head and neck, but patients with a negative sentinel node need to be counseled about the possibility of regional recurrence and undergo appropriate follow-up. Usually, physical examination of the lymph nodes is sufficient, but future studies may want to investigate whether ultrasound follow-up might be helpful for selected patients considered at higher risk of regional failure.

But even among sentinel node-negative patients with no sign of regional nodal recurrence, distant metastasis of melanoma was occasionally seen. In Jones’ study, 62 of 515 patients (12%) with a negative sentinel node biopsy developed distant metastasis without evidence of nodal failure. Presumably this represents hematogenous dissemination of the melanoma without concomitant lymphatic spread, but it could also be the case that there were very small metastases within the sentinel node that were not visualized by the pathologist or that the melanoma cells transited through the lymph nodes into the systemic circulation without ever developing a nodal deposit of tumor. Whatever the mechanism, sentinel node-negative patients clearly need to be aware of the possibility that their cancer can spread even if it never shows up within the lymph nodes.

The optimum schedule for follow-up of node-negative patients remains unknown. Given the substantial risk of second primary cutaneous malignancies (both melanoma and nonmelanoma skin cancers) in patients with melanoma, periodic dermatologic evaluation is clearly an important consideration. But the results of Jones’ study and others demonstrate the potential value of periodic examination of the regional lymph nodes and assessment for signs and symptoms of distant metastasis, as well. This doesn’t necessarily mean imaging studies like CT or PET/CT scans should be routinely employed, as there is no evidence that such scans improve outcomes and there is growing evidence that these scans involve some risk. Since many — if not most — melanoma recurrences are diagnosed by the patient, it is incumbent on surgeons who perform sentinel node biopsy to inform their patients of the full story behind a negative biopsy result, and to set up a follow-up plan that includes informing patients how to proceed if they do notice signs or symptoms of regional or distant recurrence.

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