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Editorial |
Department of Surgical Oncology, Erasmus University Medical Center–Daniel den Hoed Cancer Center, 301 Groene Hilledijk, 3075 EA Rotterdam, The Netherlands
Correspondence: Address correspondence and reprint requests to: Alexander M. M. Eggermont, MD, PhD; E-mail: a.m.m.eggermont{at}erasmusmc.nl.
In this issue of Annals of Surgical Oncology, Starritt et al.1 present their experience with ultrasound (US) examination of sentinel nodes (SNs) in the initial assessment of patients with primary cutaneous melanoma. In 304 patients, histopathology of the SN revealed metastatic disease in 33 node fields in 31 patients. Only 7 of 33 node fields had been also identified by US. Metastatic deposits <4.5 mm had not been identified by US. The authors concluded that because most metastatic deposits in SNs are smaller, US is not cost-effective in this setting. The authors suggest, on the basis not of their own findings, but of the results of a study by Garbe et al.2 (which demonstrated that the ability of US to detect melanoma recurrence in lymph nodes during follow-up was greatest in stage IIb patients), that in this subset of patients with more aggressive melanomas, US of the SN in the primary assessment is likely to be positive more often and should therefore be considered. This is mixed message indicating that this chapter is not closed.
In breast cancer, it has been clearly demonstrated that US of the axilla can reduce the number of SN procedures. A multicenter study in 116 patients in Rotterdam demonstrated in 1999 that US-guided fine-needle aspiration (US-FNA) identified positive lymph nodes in 17% of clinically node-negative cancer patients. For T1 tumors, the detection rate for US-FNA was only 6%, but for T2 tumors it was 25%, and for T3 tumors it was 50%.3 This was recently confirmed in a Japanese study in 262 women, in which US was positive in 6% of T1, 20% of T2, and 70% of T3 tumors.4 These findings indicate that US-FNA can significantly reduce the number of SN procedures and that it is cost-effective in breast cancer for T2/3 tumors. Similar results were also reported by Deurloo et al.5 in 266 patients. These authors demonstrated a reduction of SN procedures of 14% in the overall clinically node-negative breast cancer population.
In melanoma, one might expect a similar situation, and indeed there are reports pointing in that direction. Rossi et al.6 published a prospective study on the preoperative assessment of the regional lymph nodes by US in 125 patients with primary cutaneous melanoma. US correctly detected 12 of 31 histologically positive lymphatic basins in the total population of 125 patients and thus avoided an SN procedure in approximately 10% of patients. Whether this 10% reduction for the total population of melanoma patients considered for SN is cost-effective remains to be shown, because no formal calculations were presented. Of note, in this article, no metastasis <2 mm was picked up by US. Starritt et al. correctly note that there is no formal proof in the report by Rossi et al. that a different node with a different-sized micrometastasis from the histopathologically reported SN was not detected by US. Still, the 10% reduction of SN procedures, as the outcome of the Rossi study stands, is not that much different from the 14% to 17% reported in overall breast cancer populations, and that result is the most important outcome. Moreover, the conclusion that the yield will be higher if one implements US only in thicker melanomas, be it thicker than 3 or 4 mm, is logical and in line with the situation for T2/3 breast cancers. It is therefore fair to state that at this point, a situation in melanoma similar to the one in breast cancer is not unlikely but needs to be formally demonstrated by study reports that can be expected to appear in the near future. A point of interest is that in patients with primary melanomas thicker than 4 mm, on the one hand, US may be have the highest detection rate, but on the other hand, the survival difference between SN-positive and SN-negative patients may not be as significant as with intermediate-thickness melanomas.7–10
It is interesting to see that we are already discussing how to reduce the number of SN procedures in melanoma patients by US, even though the benefit of the SN procedure in terms of effects on survival has not been demonstrated, because we are awaiting the results of the Multicenter Selective Lymphadenectomy Trial (MSLT)-I. Whereas in breast cancer the SN status may define the need for adjuvant systemic therapy, the situation in melanoma is different. Because the pooled data of the high-dose interferon trials failed to show a significant effect on overall survival in a recent publication by Kirkwood et al.11 and because a meta-analysis of all adjuvant interferon trials similarly demonstrated the lack of a significant effect on survival,12 high-dose interferon adjuvant therapy is almost not practiced in Europe13 and is under renewed debate in the United States.14 Thus, the routine praxis of SN procedures in melanoma patients can still be debated. The obvious benefits of SN staging in melanoma are as follows: (1) the patient wants to be optimally informed about the prognosis on which he/she can base decisions regarding treatment options; (2) SN staging is necessary to stratify patients in adjuvant trials to determine whether tumor load affects the efficacy of the adjuvant strategies under study15; and (3) it protects European SN-negative stage II patients against adjuvant interferon treatments that may be offered to them despite an excellent prognosis that would have become evident by SN staging.13
The SN procedure is here to stay, and the effect of US assessment of regional lymph nodes will only increase over time. It will do so because of further technological developments that can be expected to increase its power to detect smaller metastases and because of an increased use of follow-up in patients who have not been SN-staged, as well as in patients who were SN-staged but did not undergo a full lymph node dissection, as is foreseen in the MSLT-II trial. Small metastases are detected in follow-up with such efficiency, as has been demonstrated by Garbe et al.,2 that it seems highly unlikely that an immediate complete lymph node dissection after the diagnosis of positive SN would affect survival compared with the minimally delayed complete lymph node dissection performed when a US-diagnosed 4-mm lymph node metastasis has been demonstrated. Despite this inference, I applaud the initiative of the MSLT-II trial for its primary end point, multiple secondary end points, and biologic side studies that will create more insight into the puzzling biology of melanoma as the only way to make advances in the treatment of this disease.
Received for publication September 13, 2004. Accepted for publication October 18, 2004.
REFERENCES
for high-risk melanoma provide a worthwhile benefit? A meta-analysis of the randomised trials. Cancer Treat Rev 2003;29:241–52.[CrossRef][Medline]
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