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Commentary |
Department of Radiology, St George's Healthcare NHS Trust, Blackshaw Road, London SW17 0QT, UK
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Introduction |
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 Top Introduction References |
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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 nodeimaging 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 (99Tcm 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 radionuclideradiologist/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 NHS approximately £1300 per patient [8] and is an invasive extra staging intervention, usually requiring general anaesthesia. Nevertheless, patients (many of whom are young) want the prognostic information that SNB provides [9], whether or not it improves long-term survival and despite the lack of consensus on how best to treat them if their sentinel node contains metastases.
Breast carcinoma has received more attention, being commoner and of high public profile. The aim of SNB is to avoid unnecessary axillary nodal clearance in the 70–80% of patients who do not have nodal disease. As the standard of care in the UK at present for early disease is nodal clearance, the potential cost savings to the NHS are huge. The unknowns, though, are greater; whether to inject around the tumour or just in the overlying skin; whether drainage to internal mammary nodes is significant and if so what to do about it; whether the high technical success rates from large volume centres with well defined patient populations will be reproducible in smaller and more general hospitals; whether patients with small grade 1 or invasive ductal carcinomas should undergo axillary clearance at all. The Medical Research Council funded ALMANAC trial has completed its audit phase and is on target for recruiting patients into the outcome arm, comparing survival, costs and complications between those staged by SNB vs conventional axillary clearance. Until the results of this and other similar trials are known, SNB should not be regarded as routine management. However, it is still likely that patients will demand the procedure. Information is freely available; a search for "sentinel node" on a standard Internet search engine yields over a thousand "hits", many from centres offering the technique. It is of interest that in the USA, healthcare insurers are pushing SNB because of the belief that it is cost effective and because of patient demand.
SNB offers those patients with positive sentinel nodes entry into trials of chemotherapy sooner than by clinical/radiological staging. Better staging may mean better stratification of chemotherapy trial results. The prediction is that SNB will allow surgery and/or chemotherapy to be targeted to the patients who will benefit from them. If outcome trials do show significant survival benefits (and it is likely that they will soon for melanoma) and the UK is going to offer state-of-the-art cancer care, we will need to make SNB available to large numbers of patients.
The ALMANAC study has shown that 30 supervised cases are sufficient to reach a 90% success rate in retrieving the sentinel node with a <10% false negative rate. However, the issue in the UK is not about training per se, it is one of absolute lack of manpower. The NHS executive estimates a need for 4000 more surgeons, and the Royal College of Radiologists 1000 more radiologists just to keep up with established workloads. The British Nuclear Medicine Society estimates that approximately 70 consultants in radionuclide radiology/nuclear medicine will retire over the next 5 years. The radionuclide radiology training programme has been agreed and training centres are in the process of being accredited, but who will fill these training posts? There is a national shortage of nuclear medicine trained radiographers/technicians. Furthermore, SNB will place huge demands on already overstretched histopathology resources, particularly as multisectioning of the sentinel node, immunohistochemistry and polymerase chain reaction techniques may all be needed to detect micrometastatic disease.
Surgery and histopathology are unavoidable components of SNB, but is imaging really necessary? It is, for the following reasons. Lymphatic mapping has shown that lymphatic drainage patterns are more complex and unpredictable than thought by conventional teaching. Furthermore, lymphatic drainage may be altered by infection, trauma and previous surgery. Since blue dye is not visible on the skin, surgery using blue dye alone is limited to "predictable" drainage basins. A combination of colloid and blue dye finds approximately 10% more sentinel nodes than either technique alone. A pre-operative "road map" giving the sites and estimated depths of sentinel nodes makes dissection of difficult areas such as the head and neck and internal mammary chain much easier. In melanoma, some sentinel nodes are aberrant (outside a named drainage basin) and are not locatable without imaging. Colloid may pass rapidly through the sentinel to secondary nodes. These can be distinguished by lymphoscintigraphy, using dynamic imaging to visualize lymphatic tracks and the sequence of appearance of nodes. This is important because removal of both sentinel and secondary nodes is more extensive surgery and may cause more complications. Imaging is therefore essential in melanoma and also probably so in breast carcinoma, but requires "hands-on" supervision by the imager. Although some of the technical aspects of lymphoscintigraphy can be delegated to radiographers/technicians, responsibility for the results cannot be comfortably delegated because important and almost immediate operative decisions rest on the imaging findings. However, in the USA, the response of many centres to insufficient nuclear medicine facilities is to use blue dye and gamma probe alone. In the UK, this approach cannot be taken without an ARSAC license holder (the training requirements for which have become more stringent) and medical physics support, even if no imaging is performed.
Pre-SNB imaging with radiolabelled tumour agents could potentially detect lymph node metastases in advance and avoid the need for SNB, and future rapid on-table histological techniques might detect nodal disease so that patients could go straight on to ELND. However, with histologists debating whether PCR is necessary to detect micrometastases, none of these techniques will ever be sensitive enough. It has already been shown that 18F-fluorodeoxyglucose positron emission tomography cannot reliably detect sentinel node metastases [10]. Pre-imaging might reduce a fraction of the cases undergoing SNB, but still requires nuclear medicine resources and a fraction of a big number still leaves a big number. We have some time, but healthcare planners will need to monitor the progress of trials carefully and at some point will have to bite the bullet and divert resources. All health planning is a gamble, but current evidence points to insufficient manpower for the task ahead. Some centres are already using blue dye alone and if sufficient imaging manpower is not available, more may be tempted to do the same. The result would be a "second best" sentinel node programme that misses a proportion of sentinel nodes. Any centre wishing to undertake SNB without imaging needs to prove that this has no deleterious effect on patients. For the radiology trainee, there can be no better time to go into radionuclide radiology.
Received for publication January 29, 2001. Accepted for publication February 22, 2001.
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  A. Mallick and A. R. Bodenham Disorders of the lymph circulation: their relevance to anaesthesia and intensive care Br. J. Anaesth., August 1, 2003; 91(2): 265 - 272. [Abstract] [Full Text] [PDF]
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