When Less is Enough: Rethinking Thyroid Cancer Treatment

Published - Written by Rena Xu

Many patients with thyroid cancer who have undergone thyroid gland resection are treated with radioiodine ablation.  This practice is thought to reduce the rate of cancer recurrence and death – but it does so at a price.  Exposure to radioactive substances increases the risk of developing a second radiation-induced primary cancer.  Treatment with radioiodine is also socially isolating.  While radioactive, patients must avoid contact with others; they cannot kiss their loved ones or live in the same home as young children.  Even sharing instruments of daily living, like toilets and cars, is discouraged.

There are several compelling reasons, then, to use the lowest possible effective dose of radioiodine.  But currently there is no consensus on what that dose should be.

This week, NEJM publishes the results of two large prospective trials comparing the efficacy of low-dose and high-dose radioiodine ablation.  Both trials found no significant difference between the two doses in the rate of successful ablation achieved.  One study, by Mallick et al., was conducted in the U.K. and enrolled 438 patients with thyroid cancer of tumor stages T1 to T3, with possible lymph node involvement but no distant metastases.  Patients were randomized to receive either low-dose radioiodine (1.1 GBq [30 mCi]) or high-dose radioiodine (3.7 GBq [100 mCi]) following surgery.  The primary endpoint was the success rate of ablation, defined as a negative scan and thyroglobulin level of less than 2 ng/ml at 6 to 9 months.

The authors found that ablation was similarly successful in the two groups (85% in the low-dose group versus 88.9% in the high-dose group; P=0.24). There was a significant difference, however, in the duration of hospital isolation.  Nearly 40% of patients in the low-dose group only required one day of hospital isolation, as compared to 7.1% of those in the high-dose group; conversely, more than 36% of patients in the high-dose group had to remain hospitalized for three or more days, as compared to 13% of those in the low-dose group (P<0.001 for both comparisons).  Length of hospital stay was based on an assessment of radiation risk and clinical condition.

In addition to a shorter isolation period, treatment with the low dose resulted in a lower rates of adverse events such as neck pain and nausea as compared to treatment with the high dose (21% versus 33%; P=0.007).

Schlumberger et al. report similar results from a study conducted in France.  More than 750 patients with stage T1 or T2 tumors were randomized to receive treatment with either low- or high-dose radioiodine, and ablation success rates were assessed at 8 months.  Again, there was no notable difference in success rates between the two groups.

These studies also examined various ways to stimulate radioiodine uptake in preparation for ablation.  Both studies found no difference between withdrawing thyroid suppression and using thyrotropin stimulation.

In an accompanying editorial, Drs. Erik K. Alexander and P. Reed Larsen of the Division of Endocrinology at Brigham and Women’s Hospital raise the question of whether radioiodine ablation should be used at all for low-risk patients.  “Using 131I to achieve effective ablation…must be weighed against increasing the risk of second primary cancers and the expense and logistics of 131I administration,” they observe; “many would argue that persistent local or metastatic disease would likely be identified by elevations in serum [thyroglobulin] during initial assessment and/or subsequent follow-up, allowing for treatment modification.”

For the cases in which radioiodine ablation is indicated, however, the results of these two studies promise to change standard practice.  And by reducing the dose of radioiodine – and therefore the physical, psychological, and financial costs associated with its use – such a change may be an important step toward more discriminating treatment of an increasingly common disease.

In your current practice, how do you assess the tradeoffs of radioiodine ablation for patients of different risk profiles?  How will the findings of these studies affect your approach to treating thyroid cancer?