Multicenter Selective Lymphadenectomy Trial Research Articles

The sentinel node concept is a revolutionary advance in cancer staging and has led to a flurry of research; the second biennial International Sentinel Node Conference has just been held. Sentinel node theory states that the sentinel node (or nodes) is the first lymph node to receive drainage from a tumour, having direct lymphatic connection with the tumour site. Histological scrutiny of such a node will determine whether metastasis to regional lymph node has occurred. The term was first coined by Cabanas in 1977 [1] in the context of penile carcinoma, but gained widespread interest in 1992 when Morton et al [2] applied the technique to patients with intermediate thickness malignant melanoma. The potential lies in those cancers where surgical excision of the tumour and regional draining lymph nodes are curative for early stage disease. However, elective regional nodal clearance (ELND) benefits only the minority of patients in this group who actually have occult regional lymph node metastases, and the technique itself has significant morbidity. Sentinel node biopsy (SNB) aims to improve management by targeting ELND to only those patients who will benefit from it. Interest has focused on malignant melanoma and breast carcinoma, but feasibility studies have been performed in vulval, cervical, head and neck, colorectal and gastric carcinoma. For the theory to apply, metastases should progress in a stepwise manner to the sentinel node first, rather than to nodes randomly, and this is thought to be true in melanoma where the incidence of skip metastases is less than 1% [2]. State-of-the-art technique requires sentinel node imaging and is a good example of a new application of ‘‘old’’ technology. In a modification of the lymphoscintigraphic techniques developed in the late 1970s, radiolabelled colloids (Tc nanocolloid in the UK) are injected in or around the tumour site, and drainage patterns and sentinel nodes are visualized with a gamma camera. The nodes are then marked on the skin surface and in theatre the surgeon uses patent blue dye to identify lymphatic tracks and sentinel nodes, guided by a hand-held gamma probe. Excised sentinel nodes are then sent for histological analysis and subsequent ELND is only performed on those whose sentinel nodes contain metastases. Good communication between radionuclide radiologist/physician, surgeon and histologist is essential. Do patients benefit? We do not have the full answer yet, but we are closest to it in melanoma. It has been fiercely debated whether patients with tumours of Breslow thickness 1–4 mm, of whom 20% will have occult nodal metastases, should have wide local excision (WLE) alone or ELND. A large multicentre trial (the American Intergroup Melanoma study) of WLE plus ELND vs WLE alone demonstrated significant survival benefit from WLE plus ELND in patients below 60 years, which was greatest for non-ulcerated melanomas 1–2 mm thick [3]. A similar World Health Organisation (WHO) trial of truncal melanomas 1.5–4 mm thick demonstrated significantly better 5-year survival rates in patients with nodal metastases at ELND compared with WLE alone (48.2% vs 26.6%) [4]. When lymphatic mapping and SNB are used to identify and stage nodal basins, those with negative sentinel nodes have a significantly better disease-free 3-year survival than those whose nodes are positive (88.5% vs 55.8%) [5]. With most centres reproducing high technical success rates in retrieving sentinel nodes, SNB is now a recognized staging procedure and the American Joint Committee for Cancer has revised its staging system for melanoma to include sentinel node status. The imminent results of the Multicenter Selective Lymphadenectomy Trial should tell us whether SNB prolongs 5-year survival. Whilst that trial’s co-ordinators wish to wait before declaring SNB the standard of care for early melanoma, the WHO has already done so [6]. In the USA, ELND has been the standard of care, despite it being unnecessary in about 80% of cases. If SNB is introduced to decide who are the 20% of patients who need to go on to ELND, the projected healthcare savings to the USA are $172 million per year [7]. In the UK, where the standard of care has been WLE and ‘‘watchful waiting’’, the sentinel node procedure costs the Received 29 January 2001 and accepted 22 February 2001. The British Journal of Radiology, 74 (2001), 475–477 E 2001 The British Institute of Radiology

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