‘Overdiagnosis’ driving increased thyroid cancer incidence in children
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Thyroid cancer incidence and mortality patterns among children and adolescents worldwide mirror data for adults, suggesting overdiagnosis and a need to “explicitly recommend” against screening for the disease in asymptomatic children.
Database analyses show thyroid cancer incidence has continued to rise among children and adolescents of both sexes, whereas thyroid cancer mortality — a rare outcome for children — has remained flat. In contrast, thyroid cancer diagnosis can potentially lead to “overtreatment, lifelong care and side effects that can negatively affect quality of life,” researchers wrote in a study published in The Lancet Diabetes & Endocrinology.
“Our study suggests that overdiagnosis may be the major driver of the increases observed in incidence among children, and particularly among adolescents,” Salvatore Vaccarella, PhD, a scientist in the section of cancer surveillance at the International Agency for Research on Cancer at WHO, told Healio. “This is because of the similarity of the geographical and epidemiological patterns with those observed in adults, for which there is a consensus that overdiagnosis plays a massive role [in increased cancer incidence].”
Global incidence data
In a population-based study, Vaccarella and colleagues analyzed thyroid cancer incidence and mortality data across 49 countries and territories among children and adolescents, using three international database: the International Incidence of Childhood Cancer Volume 3 study, the Cancer Incidence in Five Continents database and the WHO mortality database. Researchers analyzed temporal trends in incidence rates, including absolute changes in rates, and the strength of the correlation between incidence rates in children and adolescents and in adults. Researchers also calculated the average annual number of thyroid cancer deaths and the age-standardized mortality rates for children and adolescents.
From 2008 to 2012, researchers identified 8,049 thyroid cancer cases from 47 countries.
Age-standardized incidence rates of thyroid cancer among children and adolescents ranged from 0.4 cancers per 1 million person-years (2002-2012) in Uganda and Kenya to 13.4 cancers per 1 million person-years in Belarus. Papillary tumor subtype accounted for most of the variability in incidence rates, according to researchers.
Overall incidence rates were less than 1.5 per 1 million person-years for children age 10 years or younger, with only small variations across countries. Researchers found that the incidence rates were almost always higher among girls boys, with incidence increasing with age for both sexes. For almost all countries, researchers observed a rapid increase in incidence between 1998 and 2002, and again between 2008 and 2012.
Country-specific thyroid cancer incidence rates for children and adolescents were strongly correlated with rates in adults, as were temporal changes in the respective incidence rates, researchers wrote.
Thyroid cancer deaths among those aged 20 years or younger were less than 0.1 per 10 million person-years in each country.
“We suggest that current recommendations in adults — which recommend against the screening of the thyroid gland in asymptomatic populations without specific risk factors — should be extended to asymptomatic children and adolescents without specific risk factors,” Vaccarella said. “More research is needed to better understand and distinguish which nodules are more or less likely to progress, and therefore deserve treatment or should undergo active surveillance.”
‘No benefit’ with universal screening
In commentary accompanying the study, Livia Lamartina, MD, a doctoral student in the department of nuclear medicine and endocrine oncology at Institut Gustave Roussy and University Paris-Saclay, and colleagues wrote that the increased incidence of large thyroid tumors that might be related to screening might also suggest a co-occurring increase in thyroid cancer in the pediatric population. However, any benefit from the diagnosis of a subclinical thyroid cancer in a child or adolescent has not been shown.
“Later treatment of clinical thyroid cancer in young adults provides excellent long-term results,” Lamartina and colleagues wrote. “By contrast, overdiagnosis might transform a child into a thyroid cancer patient for the rest of their life, and overtreatment might induce complications and possibly lead to the requirement of lifelong thyroid hormone treatment. Therefore, screening with ultrasonography should not be recommended in asymptomatic children and adolescents.”
Reference:
Lamartina L, et al. Lancet Diabetes Endocrinol. 2021;doi:10.1016/s2213-8587(20)30430-7.
For more information:
Salvatore Vaccarella, PhD, can be reached at vaccarellas@iarc.fr.
Perspective
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Jessica R. Smith, MD
This study is notable for its size and scope, with more than 8,000 cases of thyroid cancer. The incidence and mortality of thyroid cancer among children and adolescents is relatively low, although children tend to present with more aggressive disease than adults. The paper's primary conclusion is justified — universal thyroid ultrasound screening is not indicated for healthy, asymptomatic children or those children without risk factors for thyroid neoplasia. However, we need to be cautious about interpreting the secondary claim that pediatric thyroid cancer incidence is driven only by overdiagnosis, as it is somewhat circumstantial.
A 2017 study by Hyeyeun Lim, Ph.D., and colleagues (JAMA. 2017; doi:10.1001/jama.2017.2719.) showed that thyroid cancer incidence and mortality rates have increased for patients diagnosed with advanced-stage papillary thyroid cancer in the U.S. since 1974, suggesting an actual increase in occurrence. Another study, published in May 2019 (Powers AE, et al. JAMA. 2019; doi:10.1001/jama.2019.18528), using data from the Surveillance, Epidemiology and End Results (SEER) registry, found that incidence among those aged 20 years or younger increased more rapidly from 2006 to 2013. The authors suggested there may be a co-occurring increase in thyroid cancer in children in addition to enhanced detection.
Although overdiagnosis of disease plays a role in some countries, the SEER data, in both children and adults, suggest that new cancers being detected are not all slow-growing and low-risk, but they are also larger and more advanced. This supports that overdiagnosis may not be the entire story. The authors allude to this, stating that the current study does not have data on specific tumors, and more research is needed to assess which nodules are likely to progress and which are not. It also does not address how to screen children with risk factors for developing thyroid neoplasia, such as childhood radiation exposure. At present, we do not know the best way to screen these children or the long-term consequences of diagnosing thyroid cancer early in that population.
Perspective
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Juliana Austin, MD, MCR
Although I agree with limiting screening for thyroid cancer in asymptomatic children, we must bear in mind that earlier detection reduces the potential for long-term complications associated with advanced disease due to more extensive surgery and radioactive iodine therapy. Our institutional data would suggest there has not only been an increase in thyroid cancer cases, but an increase in metastatic disease, which would likely eventually require treatment. How do we determine which tumors would remain subclinical? Which risk factors put asymptomatic children and adolescents at higher risk for clinically significant disease? Future studies will need to be done to elucidate these factors.
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