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Should sentinel lymph-node biopsy be used routinely for staging melanoma and breast cancers? Charles R Scoggins, Anees B Chagpar, Robert CG Martin and Kelly M McMasters* INTRODUCTION
S U M M A RY The sentinel lymph node (SLN) is the lymph node that represents the ‘gate-keeper’ of the lymphatic basin; it is the first node to receive lymphatic drainage from the site of the primary tumor. SLN biopsy is a staging procedure and should be considered as such; it is not meant to be a therapeutic operation. The SLN can be mapped and biopsied using tracer agents (e.g. radiolabelled colloid and/or vital blue dye), which are injected around the primary tumor site. Pathologic analysis of the SLN using a combination of serial sectioning of the node, standard hematoxylin and eosin staining, and immunohistochemistry decreases the false-negative rate compared with traditional nodal processing. SLN biopsy is associated with lower morbidity than full lymphadenectomy. The SLN technique accurately reflects the metastatic status of the regional lymph-node basin; recurrent nodal disease in the mapped basin is rare following a tumor-free SLN biopsy result. The objectives of this review are to provide a current and concise overview of the current literature on SLN biopsy and describe its role in clinical oncology. KEYWORDS breast cancer, melanoma, sentinel lymph node
REVIEW CRITERIA The information for this review was obtained by searching the PubMed database using Entrez. Articles published up to 30 March 2005, including electronic early release publications were included. In addition, searches were performed on the MEDLINE database using OVID for articles published from 1 January 1975 to 1 March 2005. The search terms included “sentinel lymph node”, “lymphatic mapping”, “melanoma”, “breast cancer”, and “staging”. The abstracts of retrieved citations were reviewed and prioritized. Full articles deemed relevant were analyzed and then included in this review.
CR Scoggins, AB Chagpar and RCG Martin are Assistant Professors of Surgical Oncology, AB Chagpar is Director of the James Graham Brown Cancer Center Multidisciplinary Breast Program and Director of the Norton Breast Health Program, and KM McMasters is the Sam and Lolita Weakley Professor and Chairman of the Department of Surgery, all at the University of Louisville, Louisville, KY, USA. Correspondence *Department of Surgery, University of Louisville School of Medicine, 550 S. Jackson Street, Louisville, KY 40202, USA
[email protected] Received 27 May 2005 Accepted 26 July 2005 www.nature.com/clinicalpractice doi:10.1038/ncponc0293
448 NATURE CLINICAL PRACTICE ONCOLOGY
Many solid tumors metastasize to regional lymph nodes, including melanoma, breast, gastric, and colonic cancer. Traditionally, regional lymph nodes were analyzed for the presence of metastases by pathologic processing of complete lymphadenectomy specimens. Until the mid1990s the practice of elective or prophylactic lymphadenectomy was common for both breast cancer and melanoma; this placed a significant number of patients at risk for complications related to full nodal basin dissection (removal of the entire regional lymph-node basin), including LYMPHEDEMA and infection. In the early 1990s, Dr Donald Morton and colleagues from the John Wayne Cancer Institute introduced the concept of SENTINEL LYMPH NODE (SLN) mapping.1,2 This minimally invasive technique can be used for accurate nodal staging of solid malignancies while minimizing morbidity. SLN biopsy provides accurate prognostic information, facilitates early therapeutic lymphadenectomy, and is useful for selection of patients suitable for adjuvant therapy.3–6 The two most widely accepted clinical scenarios for SLN biopsy are melanoma and breast cancer. Most modern medical centers worldwide now offer SLN biopsy for these malignancies, yet debate continues regarding whether SLN biopsy should be routinely used in clinical practice. A review of the current literature is warranted to understand fully the role of this technology. SENTINEL LYMPH NODE BIOPSY AND MELANOMA Historical perspective
The incidence of melanoma is increasing faster than that of any other cancer.7 As with most malignancies, patient outcome is determined by a combination of clinical and pathologic factors that ultimately determine the stage of disease. The factors that affect outcome in melanoma include BRESLOW TUMOR THICKNESS, CLARK’S LEVEL OF INVASION (for melanomas ≤1 mm), primary tumor ulceration, lymph-node metastases, and
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distant metastasis.8 In fact, with the exception of metastatic status, these same factors have been shown to predict SLN metastasis.9 Indeed, nodal status is the single most important determinant of patient survival in early-stage melanoma.3,8 When melanomas metastasize, regional lymph nodes are usually the first-detected sites of spread. Furthermore, it is relatively rare for patients who develop distant metastatic melanoma to never manifest nodal metastasis at some point in time, although nodal metastasis is not always the first-detected site of metastatic disease. Of course, many patients with nodal metastasis will subsequently develop distant metastatic disease. Not long ago, patients with intermediate or thick melanomas and clinically negative (non-palpable) regional nodes were offered either elective lymph-node dissection or nodal observation. The lack of survival benefit and the risk of significant morbidity from elective lymph-node dissection led investigators to pursue SLN biopsy. Current management
SLN biopsy is widely accepted as an accurate method of staging regional lymph-node basins, and has been shown to reflect accurately the true metastatic status of the entire basin.10–12 No other clinical or pathologic factor provides the same degree of prognostic information as SLN biopsy.3 Despite the accuracy of SLN biopsy in documenting the nodal-basin status, up to 15% of patients will develop metastatic disease and die without histologic evidence of nodal metastasis.13–15 This is poorly understood; however, it is known that some patients’ melanoma will metastasize beyond the regional lymph nodes without detectable nodal metastases. The most common site of failure following a negative SLN biopsy is within the nodal basin itself; this pattern of recurrence is found in approximately 6–9% of patients whose results were negative after undergoing SLN biopsy.13,14 Some authors have suggested that SLN biopsy might not be valuable, since it has not been shown to improve survival.16,17 However, SLN biopsy is an accurate staging tool that provides significant prognostic information. No other staging modality is scrutinized for therapeutic benefit, including CT, chest radiography, and MRI. SLN biopsy is an accurate and minimally invasive staging test; it should not be expected to provide a survival benefit in order to be considered valid and clinically useful.
Table 1 Selected series investigating identification of the sentinel lymph node in melanoma. Study and referencea
Study size (number of patients)
SLN identification (%)
Albertini et al. (1996)50
106
96%
Gershenwald et al. (1999)3
612
93%
1145
98%
3076
99.8%
Sumner et al. Chao et al.
(2002)51
(2004)52
aAll
these studies used both radioisotope and vital blue dye labeling. SLN, sentinel lymph node.
Technical issues Most surgeons use the combination of radioisotope localization and vital blue dye mapping to ensure accurate identification of the SLN (Table 1). This combination can be especially useful in identifying SLN at unusual sites (sometimes outside traditional cervical, axillary, and inguinal nodal basins) and in patients with multiple draining basins. Truncal and distal extremity melanomas may drain to multiple basins, and multiple-basin drainage patterns appear to negatively impact survival18 (Figure 1). For these reasons, it is useful to obtain a preoperative LYMPHOSCINTIGRAM (nuclear medicine scan) to identify the lymphatic drainage patterns prior to SLN biopsy. Approximately 5% of patients with thin melanomas (
