Abstract
I want to congratulate Mazeh and Sippel (1) for their comprehensive review on familial nonmedullary thyroid carcinoma (FNMTC). However, their conclusion that FNMTC is an aggressive disease and needs to be treated in a more aggressive manner is regrettable.
In the authors' elaboration on the existing literature, the recommendation section appears somehow disconnected from the rest of the article. Indeed, references 11, 14, 16, 18, and 19 conclude that FNMTC exhibits similar behavior to sporadic disease. In what appears to be a fifty–fifty situation, the authors focused on the data that best suited their recommendations but offered no explanation as to why the remaining data are less reliable. In this context, one would have expected an analysis of differences in methodology among the studies, at least for the two larger case–control reports (2,3).
In the study of Alsanea et al. (2), which the authors consider pivotal, 48 patients with FNMTC, 31 from the United States and 17 from Japan, were evaluated using a case–control design. Importantly, no significant differences were found between the patients with FNMTC or sporadic thyroid cancer in rates of extraglandular extension, lymph node involvement, or distant metastases. A larger case–control study by our group including 67 patients yielded similar results (3). However, the recurrence rate of FNMTC was significantly higher in the study of Alsanea et al. (44% vs. 17% for sporadic disease) than in ours (32% vs. 26%, respectively), and the mortality rate was surprisingly high (6% vs. 2% in Alsanea study, not reported in ours). Mazeh and Sippel (1) then refer to a study showing no difference in life expectancy between affected and nonaffected family members, except in families in which three or more members were affected (4), while recognizing the limitations of using survival as an end point in patients with thyroid cancer.
There are three possible explanations for the difference in recurrence rates between the study of Alsanea et al. and ours. First, in both studies, the samples may have been too small to reach definitive conclusions. Second, in the 11-year period that elapsed between the two studies, there were milestone changes in the diagnosis and treatment of thyroid cancer. Third, the study of Alsanea et al., which included patients from Japan and America, may have been biased by the different genetic backgrounds of the populations and the different approaches to disease management in the two countries. Indeed, only 35% of the Japanese patients in their series underwent total thyroidectomy, and none received radioactive iodine therapy. By contrast, our study included a homogeneous population treated in a similar manner at a single institution.
At variance with previous data, a smaller study by Mazeh, Sippel, and colleagues (5) of 37 patients with FNMTC is the only case–control study to report significant differences in extraglandular extension and lymph node involvement between FNMTC and sporadic disease. It also showed a higher rate of recurrence for FNMTC (24% vs. 12% for sporadic disease).
In addition, the authors evaluated three population-based studies with samples numbering 3000–6000 (1). In these studies, similar rates of extraglandular extension, lymph node involvement, or distant metastases were reported for FNMTC and sporadic disease. Two of them found FMNTC to have a higher recurrence rate, whereas the third did not. However, these studies lack the strength of a case–control design.
Finally, in the management section of the article (1), the authors deduce that total thyroidectomy is recommended for patients with FNMTC and that routine central lymph node dissection should be performed in all patients with tumors larger than 1 cm. However, in doing so, they do not refer to specific clinical guidelines but, rather, their own publications, disregarding all the conflicting data from the previous sections.
In support of their recommendations, the authors included a study presented at the European Society of Endocrine Surgeons congress in 2010 (6). This was a noncomparative survey from the German Society of Endocrine Surgeons showing lymph node involvement in no more than 33% of FNMTC patients, 95% of whom were disease-free after a 7.2-year follow-up period.
Overall, one can at most argue the point that FNMTC may have a more aggressive clinical course. However, as shown by the authors, and in contrast to their conclusions, the available data are not sufficient to support a more aggressive approach.