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LETTERS TO THE EDITOR |
Gastric and Mixed Tumor Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York
We very much appreciate the thoughtful comments of Dr. van Leeuwen and colleagues regarding our article entitled "Prediction of Nonsentinel Lymph Node Status in Melanoma".1 At this point, given the widespread acceptance of lymphatic mapping and sentinel lymphadenectomy in the staging of patients with primary cutaneous melanoma, two critical questions remain. The first is what, if any, benefit accrues to patients undergoing completion lymph node dissection? The second is can any patient population be identified based on characteristics of the primary melanoma and sentinel node that would be predicted to have a negligible risk of additional positive nonsentinel node at completion lymph node dissection?
Clearly, all retrospective series published to date attempting to address these questions suffer from a similar flaw, i.e., that nonsentinel nodes are generally examined with a single hematoxylin and eosin section, not routinely subjected to the rigorous review of immunohistochemistry or step-sectioning, and less often by the research procedure of molecular staging by reverse transcriptase-polymerase chain reaction, to ascertain the presence or absence of various levels of melanoma in the nodes.
However, it is not at all clear that all disease in sentinel and nonsentinel nodes shares the same clinical implications. It may well be that very low volume disease may not have the same clinical locoregional relevance as lymph nodes with higher tumor burden.
In our article, we attempted to develop a model to predict nonsentinel lymph node status using easily reproducible observations. Using this model, our data suggested that patients with nonulcerated melanomas and small (<2 mm) tumor deposits were much less likely to harbor positive nonsentinel nodes than those patients with positive sentinel nodes in the setting of ulcerated melanomas and/or large sentinel node tumor deposits. In our review, no patient with a Size/Ulceration score of 0 had a positive nonsentinel lymph node, with a 95% confidence interval of 0–14%.
In the experience of Dr. van Leeuwen’s group, fully 19 of 71 patients with positive sentinel nodes were found to have positive nonsentinel nodes, a rate of 26.7% (95% confidence limits ± 10%). This is slightly, although not statistically higher, than the quoted incidence in our Table 5 and higher than the 16% incidence quoted by Dr. McMasters in the Sunbelt Melanoma trial,2 as well as by Dr. Thompson from the Sydney Melanoma Unit.3 As in our model, the authors’ model for predicting nonsentinel node positivity includes incorporation of both primary tumor thickness, a reproducible measurement, as well as sentinel lymph node tumor area, a factor that we are skeptical can be reliably reproduced in community pathology departments. The authors reiterate the observation of others and ours that burden of disease in the sentinel node is an important predictor of clinical outcome.
As pointed out by the large series from the Sunbelt Melanoma trial and the Sydney Melanoma Unit, it is quite unlikely that we will ever develop a model to predict the biologic behavior of melanoma based solely on characteristics of the primary tumor and sentinel nodes at the light microscopic level. As it is unlikely that we will ever define a group of patients at zero risk for sentinel lymph node metastasis, it is also extremely unlikely that we will ever define a group of patients at zero risk for nonsentinel lymph node metastasis. Furthermore, developing a model to predict a low-risk of nonsentinel lymph node metastasis, as a rationale to guide therapy, may be over-simplistic. We still do not know what, if any, benefit completion lymph node dissection offers the individual patient. We clearly need a more sophisticated understanding of the biology of the primary tumor to predict both its regional and distant metastatic potential. Only then will we be able to refine a more rational strategy to manage these patients.
REFERENCES
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