Abstract
Preparation of patients with well-differentiated thyroid carcinoma for 131I remnant ablation with recombinant human thyrotropin (rhTSH) has advantages over withdrawal of levothyroxine (L-T4), including the preservation of quality of life, shorter absence from work, a shorter hospital stay, prevention of symptoms and eventual complications of hypothyroidism, lower radiotoxicity (1), and reduced exposure to elevated TSH (2) associated with a potentially lower risk of tumor growth. The efficacy of rhTSH for remnant ablation has been evaluated in various studies by the administration of a low or high 131I activity, and even in patients who are at high risk of recurrence (1,3,4). In all of these studies, the results of ablation were evaluated in the first year after treatment. Although the findings of this control assessment are predictive of patient evolution over subsequent years, studies comparing the long-term recurrence rate between patients prepared with rhTSH versus hypothyroidism are needed. Few series have so far reported the rate of tumor persistence or recurrence after medium-term follow-up for patients prepared with rhTSH.
Therefore, the objective of the present study was to compare the evolution of patients prepared with rhTSH versus L-T4 withdrawal for remnant ablation after a minimum follow-up of 5 years, a period during which most cases of recurrence occur.
Since the data (results of thyroglobulin [Tg], anti-Tg antibodies [TgAb], and TSH measurement, imaging methods, cytology, and histology) were analyzed in December 2010 and a minimum follow-up was required, only patients submitted to ablation with 131I between August 2003 (when rhTSH started to be used at our institution for this purpose) and December 2005 were evaluated. Patients with well-differentiated thyroid carcinoma undergoing total thyroidectomy (apparently complete tumor resection) were selected. Patients with microcarcinomas restricted to the thyroid (no indication of ablation) were excluded. The few cases in which post-therapy whole-body scanning (WBS) detected metastases were also excluded. A total of 276 patients met the selection criteria. Only nine of these patients were lost or died of a cause unrelated to thyroid cancer before completing the 5 years of follow-up. Thus, the final sample consisted of 267 patients (79 patients prepared with rhTSH [group A] and 197 submitted to L-T4 withdrawal [group B]). The study was approved by the Research Ethics Committee of our institution.
The groups (A and B) were similar in terms of gender, age, histology, tumor stage, 131I activity administered, and time of follow-up (see Supplementary Data; Supplementary Data are available online at
The follow-up of patients without initially apparent disease revealed recurrence in four cases of group A (5.2%) and in eight of group B (4.2%) (p=not significant [ns]). Thus, at the end of follow-up the rates of persistent or recurrent disease were 8.9% and 8.1% in groups A and B, respectively (p=ns). In group A, metastases were diagnosed on average 24.8 months after ablation; of these, 85.7% were cervical metastases and 71.4% were detected by ultrasonography (US), 14.3% by fluorodeoxyglucose–positron emission tomography (FDG-PET)/computed tomography (CT), and 14.3% by RxWBS. In group B, metastases were detected on average 22.5 months after initial therapy; of these, 81.2% were cervical metastases and 75% were diagnosed by US, 12.5% by FDG-PET/CT, and 12.5% by RxWBS. There was no case of disease-related death during follow-up.
The behavior of tumor markers (Tg and TgAb) in patients without apparent disease during follow-up was similar in the two groups (See Supplementary Data). The percentage of patients who had never had disease at the end of follow-up and who presented Tg<1 ng/mL and negative TgAb was similar in groups A and B (68 [86%] vs. 168 [85.2%], respectively [p=ns]), as was the percentage of those with elevated Tg or positive TgAb, although Tg and TgAb levels were reduced (4 [5%] vs. 13 [6.6%], respectively [p=ns]). At the end of follow-up, 17/24 nonablated patients of group A (70.8%) were apparently cured (i.e., stimulated Tg<1 ng/mL, negative TgAb, and no apparent disease) versus 50/68 patients of group B (73.5%).
In conclusion, the results of this study confirm that preparation with rhTSH is as effective as L-T4 withdrawal for remnant ablation after total thyroidectomy. In addition, the rate of long-term recurrence (minimum follow-up of 5 years), the behavior of tumor markers (Tg and TgAb) during follow-up, and the rate of late complete remission in patients initially not ablated were similar for the two preparations.