Abstract
We appreciate the comments by Drs. Benbassat, Malchoff, and McDonald (1,2) in response to our recent review on familial nonmedullary thyroid cancer (FNMTC) that was published in the September issue of Thyroid (3), and are thankful for the opportunity to highlight and emphasize a number of issues.
Dr. Benbassat's comments focus on the recommendations regarding extent of initial surgery for FNMTC patients and the recommendation for a central neck dissection in this cohort. As Dr. Benbassat accurately states, the studies reviewed in our manuscript are of conflicting conclusions. At present, the sum of the data appears to be a 50:50 split between those studies that show that FNMTC is more aggressive and those that show no difference, and it is true that the study published by Benbassat's group did not demonstrate increased tumor aggressiveness between sporadic and FNMTC patients (4). However, our suggested approach is based on several considerations.
First, as mentioned in the text, it is important to emphasize that given the paucity of data and the rarity of this condition, these recommendations are at best grade C, as they rely on case-control studies, retrospective studies, or expert opinion. Thyroid readers should therefore consider any conclusion or recommendations within this context.
Second, we want to emphasize again that the number of family members affected and the nature of the disease within the family need to be considered. As correctly pointed out by Malchoff and McDonald, kindreds with only two FNMTC patients probably include a significant number of patients with sporadic disease, hence diluting any possible differences. When the analysis is focused on a kindred with more affected members, the chances for sporadic disease decrease (5). As highlighted in their response, when using statistical methods to control for the variability in true disease incidence amongst cohorts, the aggressiveness of FNMTC becomes more apparent.
Third, we believe that the small numbers involved in the currently available literature preclude disease survival from being a significant endpoint. However, we believe that disease recurrence is a very clinically meaningful endpoint for these patients, as it may lead to additional intervention and affects patients' quality of life. In addition to the four studies we included in our review, an additional study has recently been published showing that FNMTC is associated with a significantly higher risk of disease recurrence (6).
As there is evidence for increased lymph node involvement and higher rates of recurrence in patients with FNMTC, we believe that there may be value in performing a central lymph node dissection in this cohort. Prophylactic central neck dissection for papillary thyroid cancer is standard practice at many institutions, while other institutions perform it selectively in only high-risk patients. For those surgeons who only perform it selectively, it is important to identify high-risk cohorts who would potentially benefit most. Given the available data, we think it is reasonable to consider FNMTC patients a higher risk subgroup that may benefit from the inclusion of a central neck dissection in order to help decrease recurrence rates. In order to minimize the risks associated with this strategy, we strongly recommend that patients with FNMTC be referred to tertiary endocrine surgery centers, as complications significantly decrease when lymph node dissection is performed by highly experienced surgeons.
The data on FNMTC are clearly mixed, but after a thoughtful review of the available data, we believe that the data do support a more aggressive phenotype with a higher risk of recurrence. We believe that more aggressive initial surgical management may help to mitigate these differences and help to reduce recurrence rates in this cohort. We are in complete agreement with all authors that carefully planned future studies may shed more light on this controversial issue.