Sentinel Lymph Node Biopsy for Thin Melanomas?


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Sabel_large.jpgWhen sentinel lymph node biopsy for the regional staging of melanoma was first introduced, it was recommended for any patient with a melanoma 1.0 mm in Breslow thickness or greater. Patients with thin melanomas were not thought to have a sufficiently high risk to warrant the additional cost and morbidity of the procedure.

As experience grew, several retrospective series identified risk factors beyond Breslow thickness that were associated with an increased risk of regional metastases, and should therefore prompt consideration of sentinel lymph node biopsy for patients with melanomas shy of 1.0 mm (in a range generally considered to be 0.76 to 0.99 mm). These risk factors were quite varied and included Clark level IV, ulceration, mitotic rate, angiolymphatic invasion, and the age of the patient (with younger patients having a higher rate of sentinel lymph node metastases than their older counterparts). Findings implicating the last three of these risk factors were the most consistent.

Staging Revision

When the most recent version of the American Joint Committee on Cancer (AJCC) staging system for melanoma was released,1 one of the most significant changes was the classification of stage T1b as any melanoma ≤ 1.00 mm with ulceration or a mitotic rate ≥ 1/mm2. Despite the authors’ stressing that this decision was made based on survival data and that “the AJCC Melanoma Staging Database did not contain sufficient data to assess risk of occult nodal micrometastases in this population,” many surgeons have advocated extending the indications for sentinel lymph node biopsy to include any T1b melanoma. This would include any melanoma < 0.76 mm with a mitotic rate of at least 1/mm2.

Performing sentinel lymph node biopsy even for intermediate-thickness melanoma remains slightly controversial, as the Multicenter Selective Lymphadenectomy Trial-1 (MSLT-1) has yet to demonstrate an overall survival benefit for the addition of sentinel lymph node biopsy to wide excision of intermediate-thickness (1.2–3.5 mm) melanoma.2 This is primarily because any potential benefit is limited to the node-positive population (16% in the MSLT-I trial) and subset analysis suggests the benefit is only around 10% to 15%. As the likelihood of finding regional metastases decreases, the benefit of the procedure also decreases, and the risk-benefit ratio tilts more toward risk.

Statistical Extrapolation

Advocates for sentinel lymph node biopsy for thin melanoma state that T1b melanomas have a sufficient risk, but this is based on statistical models extrapolated to thin melanomas. A careful analysis of papers advocating sentinel lymph node biopsy for thin melanomas show most if not all potential benefit is limited to patients with melanomas between 0.75 and 0.99 mm, the group for whom we currently recommend consideration. Retrospective series consistently show a sentinel lymph node positivity rate of only 2% to 3% for melanoma < 0.75 mm.3 As these patients were specifically selected for sentinel lymph node biopsy based on adverse features, this may even overestimate the risk among the entire T1b population.

Even if we assume a 2% to 3% risk and extrapolate the same 10% to 15% benefit among the node-positive subset (which itself is a leap of faith), one would have to perform well over 300 sentinel lymph node biopsies to benefit one patient. As the addition of sentinel lymph node biopsy to wide excision significantly increases both the costs and the morbidity, it is difficult to justify this approach.

Conclusions

Data from large national databases suggest that sentinel lymph node biopsy is only being used in a fraction of patients with intermediate-thickness melanoma—those patients most likely to benefit from the procedure.4,5 At this time, our efforts and resources are better spent addressing the utilization of sentinel lymph node biopsy among this population. In addition, we should continue our attempts to identify clinical, molecular, or proteomic markers associated with a sufficient risk of regional metastases among patients with melanomas < 0.75 mm so as to identify a subset of those who should be offered the procedure. Until that time, the standard recommendations for sentinel lymph node biopsy (melanoma ≥ 1 mm or 0.76–0.99 mm with adverse features) should not be extended to include all T1b patients. ■

Disclosure: Dr. Sabel reported no potential conflicts of interest.

References

1. Balch CM, Gershenwald JE, Seng-jaw S, et al: Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol 27:6199-6206, 2009.

2. Morton DL, Thompson JF, Cochran AJ, et al: Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med 355:1307-1317, 2006.

3. Andtbacka RH, Gershenwald JE: Role of sentinel lymph node biopsy in patients with thin melanoma. J Natl Compr Canc Netw 7:307-317, 2009.

4. Lane K, Kempf A, Magno C, et al: Regional differences in the use of sentinel lymph node biopsy for melanoma: A potential quality measure. Am Surg 74:981-984, 2008.

5. Bilimoria KY, Balch CM, Wayne JD, et al: Health care system and socioeconomic factors associated with variance in use of sentinel lymph node biopsy for melanoma in the United States. J Clin Oncol 27:1857-1863, 2009.

Dr. Sabel is Associate Professor of Surgery at the University of Michigan Health System and Director of the University of Michigan Comprehensive Cancer Center Breast Cancer Clinical Outcomes Project, Ann Arbor.



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