In a recent issue of Cancer, Pasquali et al presented a personal series and literature meta-analysis that concluded that, in melanoma, early lymphadenectomy for sentinel lymph node (SLN)-positive patients improves their survival advantage when compared with delayed lymphadenectomy when lymph node disease becomes clinically evident. 1 Their analysis assumes that every positive SLN, even when minimally involved, will inevitably progress to palpable lymph node recurrence if not removed. The authors do not consider the possibility of prognostic falsepositivity, 2 meaning tiny deposits of melanoma in the SLN that may be of no adverse prognostic significance and may be destined for dormancy or destruction rather than disease progression.
Breast cancer is the other disease in which prognosis and treatment is governed by SLN status but in which prognostic false-positivity is recognized. Micrometastases measuring <0.2 mm in greatest dimension are accepted as being of no adverse prognostic significance and are not an indication for axillary lymph node dissection nor necessarily for adjuvant chemotherapy. 3 Why should the biological significance of micrometastases in the SLNs of patients with melanoma and breast cancer be considered so differently?
To the best of my knowledge, the first study to report the survival benefit of early versus delayed lymphadenectomy was the ''matched pair'' analysis. 4 In that study, a survival advantage of 22%, 32%, and 37%, respectively, at 5, 10, and 15 years was claimed for early lymphadenectomy based on a comparison of 2 groups of patients matched for all other prognostic factors. How can this large survival advantage be reconciled with the lack of any difference in overall survival from the point of randomization in the Multicenter Selective Lymphadenectomy Trial-1 (MSLT-1) trial, the defining randomized controlled trial? 5 Surely the most likely explanation is that in the ''matched pair'' analysis, and in most of the other studies quoted by Pasquali et al, there was a significant prognostic difference between the 2 groups of patients whose survival was compared. In other words, a propor-tion of patients who underwent early lymphadenectomy were prognostically false-positive for lymph node disease.