Reply to False-positivity in the sentinel lymph nodes in melanoma and breast cancer


We agree with Dr. Thomas that the issue of the therapeutic value of sentinel lymph node biopsy (SLNB) is a challenging one and that the interim analysis of what to our knowledge is the only randomized controlled trial (RCT) performed to date to address this issue (the Multicenter Selective Lymphadenectomy Trial-1 [MSLT-1]) is negative. However, we should also acknowledge that the MSLT-1 was not properly designed to assess the effect of SLNB-guided lymphadenectomy on the survival of melanoma patients; in this regard, the MSLT-2 should provide us with a better understanding of the role of SLNB in the management of this disease. In the interim, it is fair to analyze the data at our disposal and make some considerations.

First, with regard to our personal retrospective series,1 the use of multivariate survival analysis should temper the concerns regarding potential biases of unbalanced prognostic factors.

Moreover, we defined survival times starting from the date of the primary melanoma diagnosis and not from the date of the SLNB or that of the elective radical lymph node dissection (RLND). This approach avoids any difficulty in considering 2 different timepoints during the natural history of the disease and thereby eliminates another potential bias while computing the difference in survival between the SLNB-based strategy and the elective RLND strategy.

It is interesting to note that the statistical power of our analysis (based on 190 patients) was below the desirable 80% to detect a hazard ratio <2, which led us to perform the meta-analysis of the available data. As we have reported, the pooling of the summary data of the relevant evidence is in favor of the use of the SLNB-based strategy in terms of overall survival benefit. Although we realize that only a dedicated, well-designed, and properly analyzed RCT can solve this dilemma, we still believe that it is fair to analyze the data generated to date by the scientific community and is reasonable to trust the findings of this analysis until higher level evidence is provided.

Finally, with regard to the issue of the prognostic value of isolated tumor cells (ITC) in melanoma, we must disagree with Dr. Thomas; in fact, our meta-analysis of the role of molecularly determined minimal residual disease in the SLNs does support the prognostic role of ITC.2

Simone Mocellin MD, PhD*, Sandro Pasquali MD*, * Department of Oncological and Surgical Sciences, University of Padova, Padova, Italy.