Radioiodine Ablation in Patients with Low-Risk Thyroid Cancer
The administration of radioiodine (131I) has traditionally been part of therapy to patients with thyroid cancer after thyroidectomy; however, it is unclear whether this administration provides any benefit after a complete surgical resection. Also, radioiodine is not recommended in patients with disease that is categorized as consisting of a tumor <1 cm in diameter and clinical stage N0 (low-risk thyroid cancer).
This investigation [N Engl J Med. 2012;366(18):1663-1673 ] was a randomized, phase 3 trial in which the authors aimed to determine whether the rate of successful postoperative thyroid ablation would be similar among euthyroid patients receiving recombinant human thyrotropin or among hypothyroid patients undergoing thyroid-hormone withdrawal and among those receiving low (1.1 GBq) or high (3.7 GBq) 131I radioactivity.
The investigators, representing 24 medical facilities in France, had the following inclusion criteria: ≥18 years of age, low-risk differentiated thyroid carcinoma (papillary or follicular, excluding aggressive histologic subtypes), tumor-node-metastasis stage, ascertained on pathological examination (p) of a surgical specimen, of pT1 (tumor diameter ≤1 cm) and N1 or Nx or pT1 (tumor diameter >1 to 2 cm) and any N or pT2N0, absence of distant metastasis, Eastern Cooperative Oncology Group performance status score of 0 or 1 (fully active and able to carry on all predisease performance without restriction, and restricted from physically strenuous activity but ambulatory, respectively), no major coexisting conditions (including other cancers) within the previous 5 years, a negative pregnancy test for women, and no iodine contamination.
All patients underwent total thyroidectomy. Lymph-node dissection was performed in patients with evidence of lymph-node involvement, as well as in some patients with no evidence of lymph-node involvement, if part of local practice. Patients were randomly assigned to undergo 1 of 4 strategies, each combining 1 of 2 methods of thyrotropin stimulation―administration of recombinant human thyrotropin or thyroid-hormone withdrawal―and 1 of 2 131I activities
(1.1 GBq or 3.7 GBq).
Randomization was performed between 30 and 120 days after surgery, during which time patients received levothyroxine therapy for at least 28 days (or levotri-iodothyronine therapy for 14 days).
Primary outcome was thyroid ablation, assessed at 8 months after radioiodine administration with the use of neck ultrasonography and determination of the level of recombinant human thyrotropin-stimulated serum thyroglobulin or a diagnostic 131I total-body scan with 148 to185 MBq in patients with detectable antithyroglobulin antibody. Ablation was considered complete if both the neck ultrasound was normal and the level of recombinant human thyrotropin-stimulated thyroglobulin was ≤1 ng/mL (or, in cases of detectable antithyroglobulin antibody, if the control 131I total-body scan was normal).
A total of 752 patients were enrolled from April 2007 to February 2010; 23 did not receive radioiodine ablation. After surgery and before radioiodine administration, the 729 remaining patients received thyroid hormone therapy for a mean of 91 days in the groups receiving recombinant human thyrotropin and 70 days, followed by withdrawal of thyroid hormone for 20 days, in the groups undergoing thyroid hormone withdrawal.
At the time of 131I administration, the serum thyrotropin level was >30 mIU per liter in 343 of the 360 patients (95%) in the thyroid hormone withdrawal groups. Radioiodine uptake in the thyroid bed was >0.5% of the administered radioactivity in 590 of the 729 patients (81%). Persistent disease was diagnosed in 27 patients with the use of post-ablation total body scanning (14 patients), post-ablation total-body scanning and neck ultrasonography (8), or neck ultrasonograph only (5).
On follow-up, thyroid ablation was considered complete in 631 of the 684 patients (92%). The rates of complete ablation showed that the 2 treatments were equivalent.
