Radioiodine for Thyroid Cancer: Less Is More

Zosia Chustecka

May 03, 2012

May 3, 2012 — A change in the standard treatment for low-risk thyroid cancer is heralded by 2 large trials showing that the results with low dose radioiodine are similar to those with a higher dose after thyroidectomy.

The findings from these 2 studies are reported in the May 3 issue of the New England Journal of Medicine.

There is still a question of whether any radioiodine is necessary after surgery, so for now, "less can indeed be more," according to an accompanying editorial.

"Defining optimal therapy for patients with low-risk thyroid cancer is challenging," write editorialists Erik Alexander, MD, from Brigham and Women's Hospital, and Reed Larsen, MD, from Harvard Medical School, both in Boston, Massachusetts.

It is important because the incidence of low-risk thyroid cancer has increased dramatically in recent years — likely because of better detection. In addition, unlike many other cancers, thyroid cancer affects young adults, and the consequences of treatment will affect them for the rest of their lives.

The incidence of low-risk thyroid cancer nearly tripled in the United States from 1973 to 2002 (from 2.7 to 7.7 cases per 100,000); similar increases have been reported in Europe, the editorialists note.

Radioiodine Ablation Widely Used

The standard treatment for low-risk thyroid cancer is total thyroidectomy followed a few weeks later by a dose of radioiodine, taken as an oral capsule. The radioactive iodine destroys any remaining cancer cells and any remaining healthy thyroid tissue.

However, with the high dose of radioiodine that is used, patients must stay in a hospital isolation unit for at least 2 days, without physical contact with family or friends, until the radiation fades. In addition, high doses of radioiodine can result in adverse effects, such as permanent dry mouth, and can increase the risk for a secondary cancer.

The lower dose of radioiodine tested in these 2 trials can be administered on an outpatient basis and is associated with a lower risk for adverse effects.

However, whether this secondary step of radioiodine ablation is even necessary, especially because surgical techniques have improved, is a subject of some controversy.

One prominent expert, Ian D. Hay, MD, PhD, professor of medicine at the Mayo Clinic in Rochester, Minnesota, has argued that for the majority of patients, it is an "overtreatment" with more chance of harm than benefit.

The editorialists note that guidelines from the American Thyroid Association conclude that the data are too conflicting to support a recommendation for or against the routine postoperative use of radioiodine in patients with low-risk thyroid cancer, whereas the guidelines from the European Thyroid Cancer Taskforce are "more favorable toward its use."

Despite this uncertainty, the practice is widespread. The editorialists report that there has been a substantial increase in the use of radioiodine ablation in the United States over the past 35 years, without any change in outcomes.

Lower Dose as Effective

Against this background, the 2 trials show that a low dose of radioiodine (1.1 GBq [30 mCi]) is as effective as a high dose (3.7 GBq [100 mCi]). "These results should change standard practice," the editorialists write.

One of these trials, conducted in 752 patients in France, was headed by Martin Schlumberger, MD, from the Institut de Cancérologie Gustave Roussy in Villejuif, France.

"It is not clear whether the administration of radioiodine provides any benefit to patients with low-risk thyroid cancer after complete surgical resection," Dr. Schlumberger and colleagues write, but "the administration of the smallest possible amount of radioiodine would improve care."

The other trial, the HiLo study conducted in 438 patients in the United Kingdom, was headed by Ujjal Mallick, FRCR, from the Northern Center for Cancer Care, Freeman Hospital in Newcastle upon Tyne, United Kingdom.

"We're delighted that this study of thyroid cancer will change international approaches to treating the disease more safely, by reducing the chance of another cancer developing later in life and other side effects," Dr. Mallick said in a statement. Because the lower does of radioiodine allows people to be treated as outpatients, they will be treated more quickly with less disruption to their lives. They will also enjoy a "much better quality of life," he said. In addition, this will save money for the National Health Service, he said.

"Reducing the radiation exposure is a major step forward," Dr. Mallick and colleagues conclude.

The next step is to determine whether radioiodine ablation is necessary, and whether it can be safely avoided in low-risk patients, they say. A randomized trial addressing this question is already under way in the United Kingdom (NCT01398085).

Two Approaches to Preparation

Both of the trials addressed another issue in the treatment of patients with low-risk thyroid cancer — how best to prepare the patient for the radioiodine ablation.

After patients undergo thyroidectomy, they need to take a thyroid hormone (levothyroxine) for the rest of their lives.

However, results are best when patients stop taking these tablets 2 to 4 weeks before radioiodine, which allows levels of endogenous thyrotropin — required to stimulate the uptake of radioiodine — to rise.

It has been a standard practice to recommend that patients stop taking levothyroxine for a while, even though withdrawal is associated with adverse effects, such as lethargy, fatigue, and weight gain.

An alternative is to continue with the thyroid hormone tablets, to avoid these adverse effects, and to administer exogenous recombinant thyrotropin (Thyrogen, Genzyme) just before radioiodine treatment.

The 2 trials compared these different approaches in addition to comparing the different doses of radioiodine.

Both studies were noninferiority trials and ultimately proved that the 2 preparation approaches are equivalent, note the editorials.

However, the authors of both studies emphasize the convenience and lack of hypothyroid symptoms with the recombinant thyrotropin.

The editorialists are not convinced. They say that the data do not clearly indicate that adding recombinant thyrotropin is better than stopping levothyroxine.

Recombinant thyrotropin costs between $2000 and $8000 and necessitates 2 extra clinic visits for intramuscular administration, with the associated costs of travel and time, they note.

"In our clinic, we often use thyroid hormone withdrawal," they note.

The French trial was supported by the French National Cancer Institute and the French Ministry of Health under the framework of the Soutien aux Thérapeutiques Innovantes et Coûteuses program. Dr. Schlumberger and coauthor Sophie Leboulleux, MD, report receiving lecture fees from Genzyme. The British trial was supported by grants from Cancer Research UK and University College London. Dr. Mallick reports serving on the board of AstraZeneca and Genzyme, and consulting for Genzyme. Coauthor Susan Clarke, FRCP, reports consulting for Genzyme. Dr. Alexander reports consulting for Asuagen and receiving research grants from Asuagen and Veracyte Dr. Larsen has disclosed no relevant financial relationships.

N Engl J Med. 366:1663-1673, 1674-1685, 1732-1733. Abstract, Abstract, Editorial


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.