Improved Detection Not Only Reason for Rise in Thyroid Cancer

Roxanne Nelson

October 10, 2013

The incidence of thyroid cancer has nearly tripled in the past 3 decades, and new findings suggest that improved detection might not be the only cause for the rising incidence.

Researchers found no significant differences in tumor characteristics — such as pathology, size, rate of local invasion, and rate of regional and distant metastases — between patients with incidentally discovered cancers and those whose cancer was found after targeted thyroid evaluation.

Notably, the researchers say, there was no significant difference in the size distribution of thyroid cancers between these 2 patient groups. "If heightened diagnostic scrutiny was causing the increased incidence of thyroid cancer, one would expect [incident] thyroid cancers to be smaller and less advanced in stage at the time of presentation," write the authors, led by Frederick Yoo, BA, from Pennsylvania State University–Milton S. Hershey Medical Center.

The study was published online October 10 in JAMA Otolaryngology–Head & Neck Surgery.

Competing Theories

The incidence of thyroid cancer was 4.9 per 100,000 in 1975; that jumped to 14.3 per 100,000 in 2009, although mortality rates have remained stable, note the researchers. The reason behind the rising incidence of thyroid cancer is unclear. Although some researchers attribute the increase to improved detection and imaging, which allows for the diagnosis of subclinical thyroid cancers, others feel that there is an actual true increase in incidence.

In particular, a number of studies have "claimed that heightened diagnostic scrutiny does not fully explain the upward trend because there is also a statistically significant increase in large-sized thyroid cancers," the researchers point out. Instead, the rising incidence may be associated with environmental or lifestyle factors that have not yet been identified, they add.

Lends Support, But More Work Needed

The most important finding "is that the average size of the incidentally discovered thyroid cancers studied was the same as the average size of the nonincidentally discovered thyroid cancers," said Raymon H. Grogan, MD, director of the endocrine surgery research program at the University of Chicago, who was approached for independent comment.

"Thyroid cancers that are found incidentally on imaging studies should come from the 'hidden' pool of insignificant thyroid cancers. If the hypothesis is correct, those hidden cancers should, on average, be smaller than nonincidentally discovered thyroid cancers," Dr. Grogan explained.

"The fact that the incidental thyroid cancers in this study were the same size as the nonincidental cancers argues against the overdiagnosis theory," he added.

As of now, there are 2 competing theories on why the incidence of thyroid cancer is rising. One is that that there is overdiagnosis secondary to diagnostic medical imaging. "If the overdiagnosis argument is correct, then a large pool of clinically insignificant thyroid cancers has to exist in the general population," Dr. Grogan told Medscape Medical News.

"Data from autopsy studies support the idea that such a pool of clinically insignificant thyroid cancers exists," he continued. "It is hypothesized that most of these hidden thyroid cancers that contribute to overdiagnosis are smaller than clinically apparent thyroid cancers."

The other theory is that there is a true rise in thyroid cancer rates secondary to a change in the biology of thyroid cancer, possibly from environmental exposure.

There are significant data in the literature that support both sides of the argument. "Our group has done a lot of work showing that overdiagnosis is probably not the only factor at work, leading to the hypothesis that there is a fundamental change in thyroid cancer biology," Dr. Grogan said.

The findings of this study do lend support to the idea that more than just overdiagnosis is causing the rising thyroid cancer rates, he added, but emphasized that these findings are not definitive. "More work needs to be done."

Significant Difference in Stage

Yoo and his colleagues hypothesized that if the increasing incidence is primarily attributed to detecting subclinical disease, then incidentally discovered thyroid cancers would be expected to be smaller and present at an earlier stage in the disease process. If the burgeoning incidence is reflective of the disease burden, there should be little difference in the size and stage at presentation between incidentally and nonincidentally discovered tumors.

To address that hypothesis, the researchers compared the clinical and pathologic characteristics of incident and nonincident thyroid cancers. They conducted a retrospective medical record review at an academic tertiary care medical center of 31 patients with incidentally discovered disease and 207 patients with nonincident thyroid cancer.

Approximately 55% of incident disease was discovered with CT scanning, 19.4% with ultrasound, 16.1% with PET imaging, and 6.5% with MRI.

There was a significant difference between the incident and nonincident groups in mean age at diagnosis (56.4 vs 41.8 years; P < .001).

There was also a difference in sex distribution. There were more men in the incident group than in the nonincident group (54.8% vs 13.5%; P < .001). Thus, the researchers note, the odds of being a male were 7.66 times as high in the incident group as in the nonincident group.

Also observed was a significant difference in TNM stage of thyroid cancer at presentation. Overall, patients with incident disease had a higher stage at presentation, with 48.4% having stage I disease, 16.1% having stage II disease, and 29.0% having stage III disease (P = .003).

Conversely, the majority of patients (76.8%) in the nonincident group had stage I disease. Although the AMES staging system did not show a significant difference between the 2 groups, the incident group had more patients with high-risk disease than the nonincident group (22.6% vs 12.6%; P = .15).

But despite the higher disease stage at diagnosis, there were no differences between the 2 groups in terms tumor size (P = .91), invasion (P = .76), lymph node involvement, or distant metastases (P > .99). This lack of difference might indicate that the overall elevation in the incidence of thyroid cancer is not solely due to the increased diagnosis of incidental cancer, they conclude, and could represent a true rise in incidence.

The authors have disclosed no relevant financial relationships.

JAMA Otolaryngol Head Neck Surg. Published online October 10, 2013. Abstract

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