Sentinel node biopsy has been enthusiastically adopted into clinical practice without a clear understanding of its benefit, which is often assumed rather than proved. Recently, the status of the sentinel node has been shown to be the most important predictor of recurrence and survival for patients with malignant melanoma. The proportion of patients who have had a negative sentinel node biopsy and who are free of disease at three years is 88.5% compared with 55.8% of patients with a positive biopsy; these groups have overall survival rates of 93% and 67%, respectively.1,2
The thickness of the tumour and whether there is ulceration remain important prognostic discriminators in patients with a negative biopsy.1 But is the ability to stratify patients prognostically enough to justify the widespread use of sentinel node biopsy or should we wait for evidence of a survival benefit after selective node dissection in patients who have had a positive sentinel node on biopsy?
Several reasons have been given to justify the use of sentinel node biopsy. Firstly, it is cheaper and causes less morbidity than elective lymph node dissection. The total cost per patient, including the cost of wide local excision, is $19 285 (£12 856) for elective lymph node dissection compared with $13 835 for sentinel node biopsy under general anaesthesia and $6853 under local anaesthesia.3 Because only 20% of patients with a primary melanoma of intermediate thickness are expected to have metastases in their regional nodes, 80% of those undergoing elective lymph node dissection are risking complications without benefit. Although these advantages of sentinel node biopsy may be applicable in the United States and Australia, elective lymph node dissection has never been widely practised in the United Kingdom, where observation and therapeutic lymph node dissection for patients who develop metastasis have been preferred.
A second argument for sentinel node biopsy is that it can be used to select patients for adjuvant therapy. But which adjuvant therapy? Currently no postsurgical therapy is effective in prolonging survival. Furthermore, when the next adjuvant treatment is defined the subsequent controlled trials are likely to prefer to recruit patients at clinical stage III to provide a quicker result. Nevertheless, the use of sentinel node biopsy to determine nodal status would be useful in excluding low risk patients with negative sentinel node biopsies from such studies of adjuvant treatments.
Thirdly, the use of sentinel node biopsy is sometimes justified as a method for selecting patients for completion node dissection on the assumption that clearing the regional node basin in patients who have had positive biopsies of sentinel nodes improves survival. This was also the justification given for elective lymph node dissection, but the results of randomised, prospective clinical trials and several historically controlled trials have found no survival advantage.4–8 One randomised controlled trial did show that there was some survival benefit among a small subset of patients who were under 60 years of age and who had melanomas 1 mm to 2 mm in thickness without ulceration.9 A multinational, randomised clinical trial, the multicentre selective lymphadenectomy trial, is in progress to validate the therapeutic efficacy of sentinel node biopsy using survival as an endpoint.10 This trial will compare survival in patients with primary melanoma who have wide local excision alone with those who have wide local excision plus sentinel node biopsy and selective completion lymph node dissection.
Sentinel node biopsy costs more and complications include seroma (3%), wound infection (3%), and allergic reactions.2 The most serious complication, however, is the potential entrapment of melanoma cells, causing a higher incidence of intransit metastasis (deposits of tumour occurring between the primary tumour site and the regional node basin).11 The sentinel node biopsy technique is not perfect, and there is the possibility of false negative results, which means that patients who have had negative sentinel node biopsies must be kept under review. The immediate false negative rate, as determined by elective lymphadenectomy performed concomitantly with sentinel node biopsy, is consistently less than 4%.1 However, when defined as a recurrence developing in the nodal basin after negative sentinel node biopsy (without completion lymphadenectomy) the false negative rate varies from 0% to 25%, depending on the length of follow up and whether immunohistochemistry was used in the initial pathological analysis of the specimen.2,12 13
A learning curve exists for this procedure for the multidisciplinary team of surgeons, nuclear medicine physicians, and pathologists, and caution should be exercised by using quality control measures and validating results. Performing 30 cases at a centre is sufficient to achieve successful sentinel node identification.10 While learning the procedure, surgeons must perform complete lymph node dissection after biopsy of the sentinel node to monitor the rate of immediate false negatives.11 Similarly, the learning curve for pathological analysis needs to include routine immunohistochemical staining of both sentinel and non-sentinel nodes because histology alone misses up to 14% of occult micrometastases.14 It is also important to select patients carefully. In general, sentinel node biopsy is recommended for patients with an estimated risk of nodal metastasis of 10% or more; these patients include those with melanomas ⩾ 1 mm or graded as Clark level IV. Clark level IV is defined as invasion into the reticular dermis but not into the subcutaneous tissue. This distinction is important when skin thickness is thin and a melanoma may be <1 mm in thickness but still Clark level IV.14
Vastly more sentinel node biopsies have been performed than have been entered into controlled trials to determine the efficacy of the procedure. If the multicentre selective lymphadenectomy trial or similar trials do not show an effect on survival, then sentinel node biopsy has no therapeutic value and patients must be informed accordingly. It is important to recognise that regional lymph node involvement may simply be a marker for more widespread disease. If no survival advantage is shown for sentinel node biopsy and selective completion lymph node dissection, it could be replaced by newer techniques including molecular reverse transcriptase polymerase chain reaction, which measures tumour burden directly in blood.10,15 These techniques could become the methods of choice for the early detection of metastatic disease.10,15 Until the answers to important questions of efficacy are obtained, those responsible for health service funding should control clinical enthusiasm by refusing to underwrite the costs of sentinel node biopsy unless all patients who undergo the procedure are entered into clinical trials.
References
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