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Low-risk thyroid cancers overtreated due to ‘epidemic in diagnosis’
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Technological advances have led to a dramatic increase in detection of low-risk papillary thyroid cancers, exposing patients to unnecessary and potentially harmful treatments, according to an analysis published in BMJ.
The incidence of papillary thyroid cancer in the United States has increased threefold in the past 4 decades, from 3.6 cases per 100,000 in 1973 to 11.6 cases per 100,000 in 2009.
However, the incidence of follicular, medullary and anaplastic thyroid cancers has remained constant during the past 30 years. Also, the death rate for thyroid cancer has remained stable at 0.5 per 100,000 since the late 1970s, researchers wrote.
The statistics provide additional evidence to support the argument that “zealous imaging” and improved technologies have “fueled [an] epidemic in diagnosis” of low-risk papillary thyroid cancers, according to Juan P. Brito, MD, a fellow of the division of endocrinology, diabetes, metabolism and nutrition at Mayo Clinic in Rochester, Minn.
Juan P. Brito
“The advances in detection are unlikely to offer any benefit, as the death rate has not changed despite the increased trend of thyroid cancer,” Brito told HemOnc Today. “Increasingly, patients are diagnosed with conditions that are not destined to cause harm, putting them at risk for unnecessary, costly and harmful tests and interventions.”
The number of thyroidectomies performed to treat thyroid cancer in the United States has increased by more than 60% during the past decade, from 16,377 in 1996 to 27,493 in 2006, Brito and colleagues reported. Those procedures cost an estimated $416 million per year, and patients who undergo thyroidectomies are at a 1% to 6% risk for further complications.
Further, the use of radioactive iodine increased from one in 300 patients in 1973 to two in five patients in 2006. A study by Iyer and colleagues that evaluated 14,589 patients who received radioactive iodine between 1973 and 2007 showed the treatment is associated with a 13% increase in the risk for salivary gland malignancies and a 5.7-fold increase in the risk for leukemia compared with patients who did not have thyroid cancer.
Papillary thyroid cancer accounts for about 85% of thyroid cancers. Researchers attributed the increased incidence to the ability of more sensitive technologies — such as ultrasound, CT and MRI scanning — to detect smaller lesions.
About 16% of CT and MRI scans conducted for reasons unrelated to thyroid cancer detect thyroid nodules, and three-quarters of them are less than 15 mm in diameter. Ultrasonography has been able to detect nodules as small as 2 mm.
However, prognosis for patients with nodules less than 20 mm in diameter is excellent. About 99% will be alive at 20 years, a stark contrast to the mortality rates of follicular (10% to 20% at 10 years), medullary (25% to 50% at 10 years) and anaplastic (90% at 5 years) thyroid cancers.
Also, patients with papillary nodules that are less than 15 mm to 20 mm and have no family history of thyroid cancer, no evidence of extraglandular invasion and no history of radiation exposure are considered to be at low risk for progression, researchers wrote.
Brito and colleagues cited a study by Davies and colleagues, who reviewed 32 years worth of data from the SEER database. Their analysis showed no significant difference in the death rate from thyroid cancer between the 35,663 patients who received immediate surgery for low-risk papillary thyroid cancers compared with the 440 patients who did not.
Brito and colleagues also cited an observational study by Ito and colleagues that included 1,395 patients with papillary thyroid cancer. Results of the study, conducted between 1993 and 2004, showed less than 25% of patients (n=340) opted for active surveillance with ultrasonography.
During follow-up, nodules enlarged by more than 3 mm in 31 (9.1%) of patients in the surveillance group. Of them, 18 underwent surgery and 13 continued surveillance. Among the 13 patients who continued surveillance, seven experienced tumor shrinkage.
“No one died in the surveillance group,” Brito and colleagues wrote. “This suggests that small papillary cancers may never progress to cause symptoms or death.”
To help reassure patients and prevent overtreatment, the researchers suggested referring to these small lesions as micropapillary lesions of indolent course (MicroPLIC), and they called for additional research to help identify appropriate treatment options for this patient population.
“Renaming low-risk thyroid lesions will convey a more adequate prognosis,” Brito said. “We should try to remove the label ‘cancer’ instead of removing indolent lesions from patients.” – by Alexandra Todak
References:
Brito JP. BMJ. 2013;doi:10.1136/bmj.f4706.
Davies L. JAMA. 2006;295:2164-2167.
Ito Y. World J Surg. 2010;34:28-35.
Iyer NG. Cancer. 2011;117:4439-4446.
Disclosure:
The researchers report no relevant financial disclosures.
Perspective
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Daniel S. Duick, MD, FACE, FACP
We don’t know the true prevalence rate of microtumors. Based on estimates and studies in the United States, prevalence rates are somewhere in the order of 5% to 7%, which would extrapolate to at least 15 million — and maybe as many as 20 million — adults in America walking down the street with microcancer in their neck.
However, the risk of death approaches zero. The risk of dying, when you look at the reverse with someone who presented with some form of extending disease, is 1%; it could have reoccurring persistent disease or grow or do something, and one in 1,000 of those patients would die. A fraction of a fraction of a fraction of 1% who have the disease could die from the disease. It’s almost nonexistent.
But to monitor it very carefully, you have to really do careful ultrasound to be sure the tumor is not growing and it’s not invading tissue space or breaching organ space (ie, the area of the thyroid capsule or onto a windpipe or vital structure). A small percentage of these are microinvasive and can be detected. Even at that point, they’re cleaned off and they do well if you detect this under real-time ultrasound.
You also have to be sure you’re looking in both lobes of the thyroid by ultrasound to ensure new nodules are not appearing and lymph nodes are not appearing laterally in the neck behind the thyroid in the neck. The tumor could remain the same size, and yet the threshold to spread to lymph nodes is very tiny.
Papillary cancer can move out of the thyroid and into a lymph node when it’s only 3 mm. It could remain in the thyroid and outside the thyroid for 20, 30, 40 or 50 years in that lymph node and do nothing, or 1% of those may grow. So it behooves people who follow microcancers to monitor the entire anterior neck. You want to know what the primary mircotumor is doing, what the opposite lobe is doing, what the lymph nodes are doing, in and around the central part of the neck and over the windpipe. What are the lymph nodes doing in the lateral part of the neck— levels 2, 3, 4 and 5?
Still, even with this, if everything is microscopic, it approaches zero for impact on people. Thus, in only a small fraction of patients is risk significant, and death is essentially nonexistent.
Louise Davies, MD, MS, assistant professor of surgery of The Dartmouth Institute, wrote an original article discussing the abundance of ultrasonographers, and the cause and effect of more detection of small nodules and microcancers (Davies L. JAMA. 2006;295:2164-2167). Of concern, however, is that over the subsequent period of 3 years, multiple papers reported a 200% to 300% increase in larger tumors (stage II to stage IV) in the United States and worldwide. This is compatible with SEER surveillance data for thyroid cancer, also showing rise in the rates of all sizes of cancer. Death rates, however, over the past 50 years, have shown to be unchanged, even with rising rates for the past 20 years of all stages of thyroid cancer.
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