Overdiagnosis Raises Concerns as the Incidence of Thyroid Cancer Cases Rises Globally

While mortality from thyroid cancer has remained relatively low over the last couple decades, the incidence of this disease continues to rise, increasing markedly in several affluent countries. Overdiagnosis, the detection of disease that may have not otherwise been diagnosed during the patient’s lifetime, may contribute to the rising incidence of thyroid cancer worldwide, suggesting overdiagnosis of thyroid cancer is now a major public health challenge, according to a study published in The Lancet Diabetes & Endocrinology.

Experts suspect the rising incidence may be related to the growing scrutiny of the thyroid gland with ultrasonography or other diagnostic techniques, but overdiagnosis may be a growing factor in the field. Overdiagnosis has been estimated to affect over half a million patients with thyroid cancer between 1988 and 2007 in 12 high-income countries. Trends show a rapid increase at the end of this study period as well, but no studies have quantified the degree of overdiagnosis in less affluent settings.

The purpose of this study was to evaluate how overdiagnosis of thyroid cancer may have progressed in high-income countries and the extent to which it may have affected middle-income countries that are undergoing a rapid socioeconomic transition. Investigators reviewed data from population-based cancer registries across 26 different countries.

All patients with thyroid cancer reported between 1998 and 2012 who were between the ages of 15 and 84 were included in the analysis. The incidence of thyroid cancer appeared to increase steadily from 1998 to 2002 and 2008 to 2012 in all high-income countries, and the same trend was also noted in less affluent countries, such as China, Columbia, Lithuania, and Belarus. This increase differed across countries, but investigators found a more marked incidence among middle-aged women between the ages of 35 and 64 years old.

The most striking distortion in the data was in the age-specific curve in South Korea; the incidence of cases in women between the ages of 50 to 59 years was more than double, from about 120 cases per 100,000 women in 2003 to 2007 to more than 260 cases per 100,000 women in 2008 to 2012. This was also 8 times higher than what was observed from 1998 to 2002, which was roughly 35 cases per 100,000 women.

Similarly, but less pronounced, this pattern was also observed in the United States, Canada, Australia, France, Italy, Lithuania, Belarus, Columbia, and China. Among these populations, the incidence accelerated in men and women from 2008 to 2012 and peaked in patients aged 45 to 54 years. During this period, 47 cases per 100,000 women and 14 cases per 100,000 men were observed. The most recent estimate of cases was higher in Lithuania at 42 cases per 100,000 women aged 55 to 64 years, in Columbia at 39 cases per 100,000 women aged 55 to 64 years, Croatia at 35 cases per 100,000 women aged 55 to 64 years, and Belarus at 35 cases per 100,000 women aged 50 to 59 years.

The study investigators also identified a historical age-specific curve of symptomatic thyroid cancer incidence prior to the introduction of ultrasonography to estimate the effects of overdiagnosis. The progressive departure of the historical pattern was attributed to the intense search for thyroid nodules in middle-aged patients that rarely lead to death.

Between 2008 and 2012, the estimated proportion of thyroid cancer cases in women was approximately 87% in South Korea, 91% in Belarus, 87% in China, 84% in Italy and Croatia, and 83% in Slovakia and France. Estimations demonstrate that over 830,000 women may have been overdiagnosed during this period across the 26 countries analyzed in this study, which included 390,000 in China, 140,000 in South Korea, 120,000 in the United States, 31,000 in Italy, and 25,000 in France.

The estimated proportions and absolute numbers of thyroid cancer cases among women attributable to overdiagnosis were lower among several countries, which were, respectively, 66% and 500 in Denmark, 65% and 600 in Norway, 63% and 500 in Ireland, 58% and 5000 in the United Kingdom, 55% and 24,000 in Japan, and 44% and 4000 in Thailand. These patterns were similarly observed in mean, although this was of a lower magnitude; over 220,000 men may have been overdiagnosed between 2008 and 2012 overall.

The contribution of thyroid cancer overdiagnosis in this study appeared to have a substantial impact on the increasing incidence of the disease overall. However, the study authors stated that the peak in incidence among middle-aged patients, the rapid increase in incidence, and the high variability between countries may reflect local medical practices.

“In South Korea, thyroid cancer overdiagnosis was a consequence of the opportunistic examination of the thyroid offered as an extra service within the context of national screening programs, whereas in other countries, overdiagnosis probably depended on the intensity of surveillance and the extent to which ultrasound and other diagnostic techniques were used,” the authors wrote. “Scrutiny of the thyroid gland is sometimes commonly done and not regulated, particularly in settings where health-care services are predominantly private and market- based, such as in many middle- income countries undergoing an economic transition.”

Thyroid cancer may also be identified incidentally during imaging techniques related to other medical reasons. Overdiagnosis was found more commonly in women than men, which reflects the systematic differences that were observed between women and men in terms of thyroid cancer incidence. Mortality was similarly low between both men and women, and the prevalence of disease identified with an autopsy was also similarly observed.

Thyroid diseases and the development of thyroid nodules may be induced particularly in women due to the interaction of the thyroid gland with a woman’s reproductive hormones, but women are also more exposed to healthcare than men, which may also lead to more opportunities for scrutiny of the thyroid gland. Another potential reason may be the risk factors, such as radiation exposure or obesity. However, the study authors noted that large and well-designed analytical studies are needed to confirm the possible effects of spatial and temporal variations in the risk factors for thyroid cancer.

“The impact of overdiagnosis on the increasing incidence of thyroid cancer highlighted in our report is thus a warning sign for countries with growing economies, where diagnostic technologies are increasingly and routinely offered, usually in exchange for payment, despite evidence that the harms far outweigh benefits,” the study authors concluded.

Overdiagnosis is a concern to healthy patients as it may expose them to unnecessary treatments, including common treatments like a total thyroidectomy, radiotherapy, and neck lymph node dissection. In addition, a small proportion of these patients experience post-surgery complications, on top of physical and psychological consequences. Overdiagnosis may also lead to substantial financial costs, as well as a diversion of resources that could impact the effectiveness, affordability, and equitability of medical services for all patients in the healthcare systems.

“In summary, our study suggests that overdiagnosis of thyroid cancer is increasing rapidly worldwide and has now become a major global public health challenge,” they wrote.

_Reference

_{Li M, Dal Maso L, Vaccarella S. Global trends in thyroid cancer incidence and the impact of overdiagnosis. Lancet. 2020 8:6, P468-470. doi: 10.1016/S2213-8587(20)30115-7}