Radioiodine for thyroid cancer--is less more?

In this issue of the Journal, Schlumberger et al.1 and Mallick et al.2 describe the administration of radioiodine (iodine-131) after total thyroidectomy in patients with low-risk thyroid cancer. Postsurgical treatment has long played an important role in the management of this increasingly common cancer.2 In the United States, the incidence nearly tripled (from 2.7 to 7.7 cases per 100,000) from 1973 through 2002.3 Similar increases have been reported in Europe.4 Such increases appear to result largely from more frequent radiologic detection and subsequent fineneedle aspiration of small thyroid nodules, leading to the diagnosis of low-risk thyroid cancer. Guidelines of the American Thyroid Association conclude that data are too conflicting to support a recommendation for or against the routine use of radioiodine postoperatively in patients with low-risk thyroid cancer,5 whereas guidelines of the European Thyroid Cancer Taskforce are more favorable toward its use.6 Despite this uncertainty, the use of radioiodine for lowrisk thyroid cancer in the United States has increased substantially during the past 35 years but without changes in outcomes.7,8 The goal of such treatment is to ablate residual thyroid, thereby improving the specificity of thyroglobulin assays and permitting detection of persistent disease by subsequent whole-body scanning. In the two carefully performed, randomized, prospective studies by Schlumberger et al. and Mallick et al., a low dose of radioiodine (1.1 GBq [30 mCi]) was shown to be as effective as a high dose (3.7 GBq [100 mCi]) in reducing thyroglobulin to a very low level and eliminating residual thyroid tissue, as seen on ultrasonography.1,2 Thyroid ablation occurred even in patients with pathologically confirmed local lymph-node involvement.2 These results should change standard practice, although they also raise the question of whether any radioiodine therapy is required for low-risk patients, since 21 to 59% of the patients in these two studies had already met the goal of a low thyroglobulin level after thyroidectomy alone.1,2 The use of radioiodine to achieve effective ablation in the remainder of patients must be weighed against increasing the risk of second primary cancers through exposure to radiation and the expense and logistics of radioiodine administration.8,9 In addition, in a recent 10-year follow-up study, the use of radioiodine did not prolong overall or disease-free survival in lowrisk patients.10 However, the omission of radioiodine therapy also precludes post-treatment whole-body scanning, which can disclose unsuspected persistent or distant metastatic disease, as was found in 3% of these patients.1 Distant metastatic thyroid cancer, especially in patients over the age of 45 years, can be a more dangerous disease. For clinicians and patients, treatment poses a difficult question: How can the standard of care be improved for the majority without sacrificing the standard care for the minority? Many observers would argue that persistent local or metastatic disease would probably be identified by elevations in serum thyroglobulin levels during the initial assessment or subsequent follow-up, allowing for treatment modification. These studies also compared strategies for preparing patients for radioiodine administration. Since thyrotropin is required to stimulate the uptake of radioiodine, two options exist: allow levels of endogenous thyrotropin to rise in re-