Sentinel node biopsy: evaluating a new technique

In breast cancer, the status of the axillary nodes is one of the strongest prognostic indicators, and a major factor in determining adjuvant systemic therapy. Although the landmark National Surgical Adjuvant Breast Project (NSABP 04) study concluded that treatment of the axilla per se did not affect long-term survival,¹ the issue of whether or not good local control (ie, radiotherapy or axillary clearance) affects survival is still debated,^2,3 and the evidence to date suggests that at least Level 2 dissection -- 10 or more nodes -- is required for reliable assessment of axillary involvement.⁴

A proportion of women will experience complications after axillary dissection, including shoulder dysfunction, paraesthesiae and chronic lymphoedema.⁵ The question then arises: can we avoid axillary clearance in selected patients -- for example, by the technique of axillary node biopsy? This technique is based on the assumption that the status of the first node in the draining basin of the primary tumour is an accurate indicator of the overall status of that field of drainage; with a tumour-free sentinel node, axillary dissection may be unnecessary.

Now that screening and evidence-based improvements to treatment are starting to have an impact on survival, we need to be wary of replacing well established methods with new techniques that have not been rigorously evaluated. Can sentinel node biopsy be implemented safely, with real long term benefits for our patients?

In this issue of the Journal , Kollias and colleagues report their results with the sentinel node biopsy technique,⁶ which compare favourably with other international series. Sentinel nodes were identified successfully in 95 of the 117 women by a combination of three techniques -- lymphoscintigraphy, blue dye and a hand-held gamma probe (the latter two for intraoperative identification).

Lymphoscintigraphy is an important prelude to sentinel node biopsy, but in the series of Kollias et al it successfully mapped the sentinel node in only 63.2% of cases. However, the authors point out that they were able to improve the accuracy by increasing the injection volume. The skill and persistence of the nuclear physician are key factors in obtaining optimal lymphoscintigraphy. In Australia, we are fortunate to have a radiopharmaceutical (^99mTc-labelled antimony sulfide colloid) that is superior to those available in other countries. This means that we may produce more accurate maps of lymphatic drainage, and thereby identify sentinel nodes more often. Research reported from the Royal Prince Alfred Hospital in Sydney has shown that drainage patterns from individual tumours can be quite unexpected.⁷ This new area of study means that we will have to re-evaluate the whole notion that "skip metastases" occur, and their significance in determining overall prognosis.⁸

If a decision on whether to dissect the axilla had been based on a confirmed tumour-negative sentinel node, then 66 of the 117 women in the study of Kollias and colleagues would have been spared axillary dissection, although in two women this would have been a false negative diagnosis (two of the 31 women with nodal involvement had sentinel nodes negative for tumour). This rate (6.5%) is comparable with those in other series.^9,10 Although we should be concerned about the false negative rate of sentinel node biopsy, we should also recognise that some occult metastases are not detected in standard haematoxylin-eosin histopathological sections. With standard staining methods, the false negative rate in a series of patients reported from St Vincent's Hospital in Melbourne was 12%; in that series, antimucin monoclonal antibodies showed micrometastatic deposits in 41 of 343 patients previously classified as having node-negative breast cancer by haematoxylin-eosin staining.¹¹

False negative assessments are inevitable when lymph nodes are sampled, but the more detailed examination of one or two "sentinel" nodes may prove more beneficial than the standard examination of many nodes. The detection of micrometastatic deposits introduces a new area of uncertainty requiring further study -- we have yet to determine their significance. How do they affect prognosis and how should we treat them? Ongoing evaluation of locoregional recurrence and distant disease is essential.

At first glance, sentinel node biopsy appears invitingly easy, but success in completing the sometimes technically difficult procedures involved will define the oncological relevance of the technique. Simply removing a "hot" or "blue" node is not enough -- we have to reappraise our indications for treating the internal mammary nodes and the supraclavicular nodes, as well as those in the axilla, as nodes from more than one site may be involved. It is equally important that women with breast cancer be managed in consultation with oncologists: women treated in a multidisciplinary setting tend to have better outcomes.¹²

While Kollias et al conclude that sentinel node biopsy is an accurate method of assessing axillary lymph node status, the accuracy has varied in other series. Reported detection rates range from 66% to 100% and false negative rates from zero to 17%.¹³ Why is there such a discrepancy? A possible explanation is the different techniques used in individual series. Some surgeons used only one method of localisation; others used different combinations of the three techniques -- different dyes, different radiopharmaceuticals, different times between injection and surgery, different methods of injection, and even different criteria by which sentinel nodes are searched for and removed.

In Australia, we have a window of opportunity to work towards a standardised approach to sentinel node biopsy, using agreed protocols and prospective and uniform data collection. Kollias and colleagues, and other representatives from the major breast units and the Section of Breast Surgery of the Royal Australasian College of Surgeons, are working together and have proposed an Australasian prospective randomised trial with the capacity to involve all surgeons who are interested in breast cancer management.

New techniques require proper evaluation. As a group, surgeons have been quick to adopt new procedures before scientific validation.¹⁴ In addition, consumer pressures, and sometimes market pressures, are at work. For comparison, consider laparoscopic cholecystectomy, which has now gained widespread approval. The learning curve was steep -- the early reports of this technique were full of enthusiasm and the procedure was adopted rapidly. There is no doubt that, in those early days, considerable morbidity for many patients could have been avoided with more caution and less haste.¹⁵ The technical aspects of these two quite different operations are not comparable; the parallel to be drawn relates to the way new procedures may be incorporated into, and perhaps finally adopted as, standard procedures. It therefore behoves us to ensure that, with any new procedure, consumers are not placed at increased risk, particularly if it is performed with limited expertise.

Owen A Ung
Clinical Services Director
New South Wales Breast Cancer Institute, and Breast and Endocrine Surgeon
Westmead Hospital, Sydney, NSW
owenuATbci.org.au

Neil R Wetzig
Chairman, Section of Breast Surgery
Royal Australasian College of Surgeons and Senior Surgeon
Princess Alexandra Hospital, Brisbane, QLD

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