Clinical Pearls & Morning Reports
Leboulleux et al. conducted a randomized, phase 3, noninferiority trial, in which patients with low-risk differentiated thyroid cancer who were undergoing thyroidectomy received either postoperative radioiodine or follow-up alone. Read the NEJM Original Article here.
Q: What is the risk of recurrence after thyroidectomy in the majority of patients with thyroid cancer?
A: The majority of patients with thyroid cancer are at low risk for recurrence (<5%), and their risk of cancer-related death is even lower. After thyroidectomy, radioiodine (iodine-131) is generally administered both to ablate residual normal thyroid tissue and to treat persistent disease.
Q: What is known about the benefits of radioiodine administration after thyroidectomy in patients with low-risk thyroid cancer?
A: There is a consensus to avoid radioiodine administration in patients with a unifocal microcarcinoma (≤10 mm in diameter), but the benefits of radioiodine administration in other patients with low-risk thyroid cancer remain controversial. In patients with pathological tumor–node–metastasis stage 1 disease, retrospective studies have shown inconsistent results regarding the usefulness of radioiodine administration. The absence of prospective studies that address this question has been used as an argument in favor of recommending the use of radioiodine in all patients with low-risk thyroid cancer.
A: The primary objective of the trial was to assess noninferiority in the no-radioiodine group as compared with the radioiodine group with respect to the percentage of patients without a functional, structural, or biologic event during 3 years after randomization. An event was a composite end point that consisted of several criteria. In the radioiodine group only, events included the presence of foci of radioiodine uptake outside the thyroid bed on postablation whole-body scanning or on SPECT (functional event) that resulted in additional treatment (radioiodine administration or surgery). In both groups, events included abnormal findings on ultrasonography of the neck (structural events), which were defined as a suspicious lymph node or thyroid mass associated with abnormal cytologic findings or with a serum thyroglobulin level in the aspirate fluid of more than 10 ng per milliliter or an elevated level of thyroglobulin or thyroglobulin antibodies (biologic events). In the two groups, the detection of a thyroglobulin antibody titer above the upper limit of the normal range or an increase in the thyroglobulin antibody titer by more than 50% between two measurements performed 6 months apart was also considered to be part of the composite criteria.
A: Among the 730 patients who could be evaluated at 3 years, the percentage without an event was 95.6% (95% confidence interval [CI], 93.0 to 97.5) in the no-radioiodine group and 95.9% (95% CI, 93.3 to 97.7) in the radioiodine group, for a between-group difference of −0.3 percentage points (two-sided 90% CI, −2.7 to 2.2), which met the noninferiority cutoff for the nonuse of radioiodine. Similar results were obtained in the intention-to-treat population and after adjustment for stratification factors. In the two groups, the patients had similar scores regarding quality of life, anxiety, distress, and fear of recurrence.