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HomeDermatologyThe Role of Sentinel Node Biopsy in Skin Cancer

The Role of Sentinel Node Biopsy in Skin Cancer

Background

The incidence of malignant melanoma is increasing rapidly, at a rate of 2-4% per year over the past decade, while the death rate is increasing less rapidly at a rate of 2-3% per year over the past decade. Malignant melanoma typically affects young patients (median age 48 y). The lifetime risk of developing melanoma for a person born in the United States is now estimated to be 1 in 27 for males and 1 in 42 for females.

Historically, the treatment of malignant melanoma has been primarily surgical, and it remains largely so for early-stage disease while exciting advances in systemic therapies are shifting treatment paradigms for more advanced disease.

The natural history of cutaneous melanoma is most often an orderly progression from invasion at the primary site, to regional lymph nodes via dermal lymphatics, and then to distant sites. If a melanoma is identified and treated at an early stage, the likelihood of synchronous lymph node metastases is quite low, and patients are usually treated with wide local excision alone. While much effort has been directed toward using molecular, cellular, and biochemical markers to determine the prognosis and appropriate treatment of melanoma,
the presence or absence of lymph node metastases, absent distant metastatic disease, remains the most powerful predictor of outcome. Numerous studies support that sentinel lymph node status is the most important independent prognostic factor with respect to disease progression and melanoma-specific survival.
Moreover, the microstaging afforded by sentinel node surgery further refines prognosis for stage III melanoma patients.

One indicator of the degree to which sentinel lymph node biopsy with selective lymph node dissection has been accepted in the staging and treatment of melanoma is the evolution of the American Joint Commission on Cancer (AJCC) staging guidelines for melanoma, which, beginning in 2004, incorporate nodal microstaging and discriminate between microscopic and macroscopic nodal disease.
Additionally, the National Comprehensive Cancer Network (NCCN) guidelines for the treatment of melanoma include sentinel lymph node biopsy with selective lymph node dissection in their treatment algorithms, and this technique has been endorsed by the World Health Organization (WHO) as well as multiple other national and international cancer treatment organizations. Over the years as this technique has gained acceptance, it has been refined.

Rationale and objectives for sentinel lymph node biopsy

The sentinel lymph node concept is that a primary or sentinel lymph node (or nodes) exists through which tumor cells from a primary tumor in a particular location first must travel to spread to a particular regional lymph node basin. A tracer substance injected into the dermis at the primary tumor site provides a roadmap leading to the sentinel lymph node(s). In addition, the hypothesis that careful examination of the sentinel lymph node(s) indicates the status of the entire lymph node basin has been validated in several studies. Thus, sentinel lymph node biopsy with selective lymph node dissection has been embraced as an alternative to elective lymphadenectomy or observation for patients with clinically negative regional lymph nodes who are at risk for nodal metastases.

The objectives of combining sentinel lymph node biopsy with or without selective lymphadenectomy in clinical practice include both decreasing the extent of the operation for selected patients and increasing the identification rate of occult lymph node metastases, thereby increasing the accuracy of staging by providing the pathologist with the lymph node (or nodes) most likely to contain metastatic disease. Historical evidence of a survival benefit for elective lymph node dissection in selected melanoma patients, as well as immunohistochemical- and molecular-based detection of metastatic melanoma in lymph nodes deemed negative by standard histopathology, implies that some patients are understaged by conventional techniques.

The WHO truncal melanoma trial (No. 14) found a significant improvement in 5-year survival rates (48% vs 26%, P = .04) for patients with clinically occult metastatic lymph nodes who underwent elective lymph node dissection at the time of wide local excision versus patients who underwent therapeutic lymph node dissection after developing clinically detectable lymphadenopathy.

In addition, a second randomized, prospective, multi-institutional study, the Intergroup Melanoma Trial, revealed a significant improvement in 10-year overall survival for patients who underwent elective lymph node dissection versus wide excision in several prospectively stratified subgroups.
Results indicated a 30% reduction in 10-year mortality rates for patients with nonulcerated melanomas (overall survival 84% vs 77%, P =.03), a 27% reduction in 10-year mortality rates for patients with melanomas from 1-2 mm thick (overall survival 86% vs 80%, P = .3), and a 27% reduction in 10-year mortality rates for patients with extremity melanomas (overall survival 84% vs 78%).

While these trials predate the rapidly shifting landscape of adjuvant systemic therapy options for melanoma patients, they provide a rationale for sentinel lymph node surgery to better stage appropriately selected clinically node-negative patients. The objective of sentinel lymph node biopsy is to identify patients who present with clinically occult regional disease. Sentinel lymph node biopsy also (1) minimizes morbidity by identifying those most likely to benefit from adjuvant therapies and/or lymphadenectomy after a minor outpatient procedure with a much diminished risk of lymphedema and other complications, (2) identifies patients who may benefit from postoperative adjuvant therapy and those who may avoid adjuvant therapy, (3) provides a means for homogeneous stratification of patients for and within randomized clinical trials, and (4) by ascertaining regional lymph node status, provides a means to assess quality and health outcome measures.

The technique of sentinel lymph node biopsy with selective lymph node dissection has been widely adopted by surgical oncologists, which has resulted in its use in the treatment of other cutaneous and noncutaneous malignancies with regional lymphatic metastatic potential.

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