The results of this study provide insight into the use of radioactive iodine for management of well-differentiated thyroid cancer. Between 1990 and 2008, there was a rise in radioactive iodine use across all tumor sizes. In addition to tumor characteristics, other patient and hospital characteristics were also associated with radioactive iodine use. There was wide between-hospital variation in radioactive iodine use and much of the variance was attributable to unexplained hospital characteristics.
Previous studies have evaluated between-hospital variation in rates of surgical procedures43,44
and the role of discretionary decision making on treatment intensity.45,46
Germane to our study is a single-institution study that evaluated use of radioactive iodine over time and found a rise in use between 1940 and 199947
and a study with Surveillance, Epidemiology, and End Results data that found increased radioactive iodine use between 1973 and 2006.21
However, our study is novel as it investigates not only treatment trends but also correlates of radioactive iodine use and variation in use in a large and recently treated multicenter cohort of thyroid cancer patients.
The explanation for the rise in radioactive iodine use across all tumor sizes is not entirely clear, but it has been hypothesized that increased detection of low risk disease can lead to overestimation of treatment efficacy and a subsequent rise in use of therapy.48
We know from previous population studies that well-differentiated thyroid cancer is increasing at a faster rate than any other malignancy with a 2.4-fold rise in incidence over the past 30 years.31,32,49
The majority of the increase is due to detection of small, low risk tumors,31,50
and, in light of the 10–36% incidence of occult well-differentiated thyroid cancer in autopsy studies,51,52
over diagnosis of clinically irrelevant cancers may be occurring.48,53
Thus, there is potential for increased detection of low risk disease spurring a rise in thyroid cancer treatment intensity.
In addition to identifying trends in radioactive iodine use and correlates of use, this study also found large hospital-based variation with patient and tumor characteristics accounting for 21% of the variation and unknown hospital factors accounting for 29% of the variation. These findings suggest disease severity is not the sole determinant of radioactive iodine use.
Wide variation in radioactive iodine use was seen in both lower and higher risk patients. The low risk patient profile depicted in is a profile in which the use of radioactive iodine was left to physician discretion12–14,16
until the most recent clinical guidelines.11
In contrast, almost all clinical guidelines would strongly recommend radioactive iodine post thyroid surgery in the high risk patient profile depicted in .11–16
The variation demonstrated in both low and high risk patients suggests clinical uncertainty.54,55
Some of this uncertainty may be explained by the lack of clinical trials evaluating the efficacy of radioactive iodine use for thyroid cancer and the conflicting single institution studies. Because of limited clinical evidence, clinical guidelines have left radioactive iodine use to physician discretion in many cases.11,12
A recent study has shown that when clinical guideline treatment recommendations are not supported by strong evidence there is less guideline-concordant care.56
Studies using a large database such as the National Cancer Database have inherent limitations. Specific to thyroid cancer, presence of extrathyroidal extension, post-operative serum thyroglobulin level, and tumor iodine-avidity are not recorded. In addition, treatment details such as dose of radioactive iodine and addition of prophylactic central lymph node dissection are not known. These missing details may be important as they can impact the indications for radioactive iodine57
and, in the case of radioactive iodine dosing, affect our assessment of intensity of care.
Even with the limitations inherent in a large database, the results of this study have implications for patients, physicians, and payers. Although appropriate therapy for select well-differentiated thyroid cancer, the benefit of radioactive iodine may not always exceed the risks. There is a clear role for adjuvant therapy with radioactive iodine in iodine-avid advanced stage well-differentiated thyroid cancer.1–3,58
however, there is unclear benefit to radioactive iodine use in low risk disease.4–6,59–64
as patients with low risk disease have an excellent prognosis regardless of intervention.5,65,66
In addition to clear cost saving benefits associated with not using radioactive iodine for low risk disease,30
limiting radioactive iodine use would decrease patients’ risks of side effects. Not only are there transient adverse effects on quality of life with the hypothyroidism typically required pre-radioactive iodine treatment,67
radioactive iodine has long term health risks. Recent studies have found increased risk for second primary malignancies after radioactive iodine treatment, even in the lowest risk patients,21
with the greatest risk for leukemia, which increases 2.5-fold.18,19,68,69
Radioactive iodine is also associated with additional adverse systemic effects, 26,17,27,70,29,16,71
and damage to local tissue, such as the salivary glands and nasolacrimal ducts.20,22,24,25
There are also potential public health risks if appropriate safety precautions are not taken at the time of radioactive iodine administration.72
In contrast to the potential for over treatment and greater harm than good when using radioactive iodine for low risk disease, the spectrum of radioactive iodine use in the high risk patient profile, suggest there may be under treatment of some high risk patients. This has potential implications for patient health, such as increased risk of disease recurrence and mortality.3,5
The fact that disease severity appears to have a small influence on radioactive iodine use after thyroid surgery is concerning. In the interest of curbing the rising health care costs and preventing both over- and under treatment of disease, indications for radioactive iodine should be clearly defined, and disease severity should become the primary driver of radioactive iodine use.
In summary, in the United States, the incidence of small, low risk thyroid cancers is growing at a faster rate than any other malignancy.49
Paradoxically, use of radioactive iodine is climbing in patients with all tumor sizes. The significant between-hospital variation in radioactive iodine use suggests clinical uncertainty over the role of radioactive iodine in thyroid cancer management. Of concern, for patients with thyroid cancer, the hospital where care is received has a substantial influence on treatment with radioactive iodine after total thyroidectomy, even after accounting for patient and tumor characteristics.