22 Aug 2013 16:54 PM
By Karen M. Devon, MD, MSc, FRCSC
University of Toronto
In 1923, Henry Plummer at Mayo Clinic first observed that iodine immediately after thyroid operation calmed the patient and hastened recovery.1 Since then, radioactive iodine was developed to treat Graves’ disease, and subsequently indications extended to thyroid cancer. Despite the very favorable outcomes associated with differentiated thyroid cancer, radioactive iodine remains one of the only therapeutic modalities for this disease besides surgery.
Other aspects of medical care, however, have changed. First, as discussed in the article that follows, the treatment of disease depends on its definition. Much of the disease—now overtreated aggressively—would not even have been detected in previous times when it was defined by clinical exam alone. Second, in an age of evidence-based care, when that evidence is lacking and side effects of a potential therapy minimal, we are increasingly pressured to “do everything” when faced with whatever is named a malignancy, even when its natural history portends a more indolent behavior.
In a time of resource and cost containment, as well as shared decision-making, it behooves us to understand the indications for radioactive iodine and thoughtfully consider these with our colleagues as well as with our patients.
Dr. Devon is an Assistant Professor of Surgery at the University of Toronto and is an endocrine surgeon at Women’s College Hospital and University Health Network in Toronto, Canada. She is interested in medical ethics and medical education.
Radioactive Iodine—Little Benefit for Patients with Low-RiskThyroid Cancer
Megan R. Haymart, MD
University of Michigan
The majority of patients with thyroid cancer have low-risk disease. There is wide hospital-based variation in radioactive iodine use for low-risk disease, suggesting that in some instances there may be overuse.1,2 Supporters of radioactive iodine use after surgery in low-risk patients would typically justify use based on one or more of the following:
- Treatment with radioactive iodine could decrease the likelihood of death,
- Treatment with radioactive iodine could decrease the likelihood ofcancer recurrence, or
- Treatment with radioactive iodine improves the ease of follow-up and decreases the amount of medical uncertainty.
I will systematically discuss the flawsin each of these assumptions.
First, does treatment with radioactive iodine decrease the likelihood of death? If this assumption is correct, it would be the most reasonable argument to encourage treatment with radioactive iodine after surgery. However, for most patients, there is no proven survival benefit, with the exception of advanced iodine-avid cancer.3,4 The overwhelming majority of patients with well-differentiated thyroid cancer are not high-risk as defined by tumor size over 4 cm, gross extrathyroidal extension, or distant metastases.5 In these lower-risk patients, no clear survival benefit has been shown.6-8 Lack of evidence should not be seen as an indication for treatment. Rather, lack of evidence should motivate further inquiry into the risks and benefits of treatment.
Second, does treatment with radioactive iodine decrease the likelihood of cancer recurrence? This is a complicated question. First, what constitutes recurrence: biochemical evidence of disease (i.e., an elevated thyroglobulin), imaging evidence of disease, or pathologically confirmed evidence of disease? An equally important consideration—is recurrence clinically relevant in affecting survival or quality of life? With improved thyroglobulin assays and increased availability of clinicians experienced with bedside ultrasounds, our ability to detect persistent/recurrent disease has improved. Nonetheless, the benefit of this improved detection is unknown. In addition, it is not clear that radioactive iodine reduces recurrence.9 Finally, recurrent cancer is usually slow growing, and even if preemptive radioactive iodine does decrease recurrence in low-risk patients, it may still be preferable to wait until there is actual recurrence and then treat with surgery or radioactive iodine as appropriate.
Third and finally, does treatment with radioactive iodine ease follow-up and decrease the amount of medical uncertainty? The answer to this question is yes, but this still may not justify use. Treatment with radioactive iodine after surgery ablates any residual normal thyroid remnant. This often leads to an undetectable thyroglobulin (tumor marker), which can then be easily followed for years. In addition, post-treatment scans after radioactive iodine administration do provide additional information on residual thyroid cancer. However, in many post-operative patients, thyroglobulin levels are less than one without radioactive iodine.10 In addition, we have bedside ultrasound and random serum thyroglobulin, which are also relatively reliable markers of persistent or recurrent disease.
Does radioactive iodine provide additional benefit? With modern technology, we can always do more to reassure ourselves. This is a slippery slope—do we also order PET/CT scans on all patients with thyroid cancer, or bedside ultrasound and random thyroglobulin every three months instead of every six months to one year? At what point are we wasting health care resources and providing little benefit to the patient? Ultimately, it depends on whether treatment with radioactive iodine for low-risk disease decreases cancer morbidity and mortality. Many physicians underestimate the effect of salivary gland dysfunction in patients who have received radioactive iodine, and if treatment with radioactive iodine does not offer survival benefit or an improvement in cancer-related morbidity in low-risk patients, then its use should be tailored to the disease severity.
Dr. Haymart is an Assistant Professor of Internal Medicine in the Division of Metabolism, Endocrinology, and Diabetes and the Division of Hematology/Oncology at the University of Michigan, where she specializes in thyroid cancer, thyroid disorders, and health services research in the area of thyroid cancer diagnosis and management.
- Haymart MR, Banerjee M, Stewart AK, et al. JAMA. 2011;306:721-8. PMID: 21846853.
- Haymart MR, Muenz DG, Stewart AK, et al. J Clin Endocrinol Metab. 2013;98:678-86. PMID: 23322816.
- Chow SM, Yau S, Kwan CK, et al. Endocr Relat Cancer. 2006;13:1159-72. PMID: 17158761.
- Jung TS, Kim TY, Kim KW, et al. Endocr J. 2007;54:265-74. PMID: 17379963.
- Cooper DS, Doherty GM, Haugen BR, et al. Thyroid. 2009;19:1167-214. PMID: 19860577.
- Podnos YD, Smith DD, Wagman LD, et al. J Surg Oncol. 2007;96:3-7. PMID: 17567872.
- Jonklaas J, Sarlis NJ, Litofsky D, et al. Thyroid. 2006;16:1229-42. PMID: 17199433.
- Schvartz C, Bonnetain F, Dabakuyo S, et al. J Clin Endocrinol Metab. 2012;97:1526-35. PMID: 22344193.
- Durante C, Montesano T, Torlontano M, et al. J Clin Endocrinol Metab. 2013;98:636-42. PMID: 23293334.
- Durante C, Montesano T, Attard M, et al. J Clin Endocrinol Metab. 2012;97:2748-53. PMID: 22679061.