Rise of Thyroid Cancer Is Oversimplified, Say Critics

Nick Mulcahy

February 21, 2014

Thyroid cancer is yet another cancer on the rise in the United States because of overdiagnosis, according to a study published online February 20 in JAMA Otolaryngology–Head & Neck Surgery.

But such a sweeping analysis is simplistic and ignores key facts, countered study critics interviewed by Medscape Medical News.

The increasing rate of the thyroid cancer over the past 30 years seems to be "not an epidemic of disease but rather an epidemic of diagnosis," say study authors Gilbert Welch, MD, and Louise Davies, MD, both from the Geisel School of Medicine at Dartmouth College in Hanover, New Hampshire.

In their report, the pair suggest that there is overdiagnosis and overtreatment of papillary thyroid cancer, and propose active surveillance as an alternative management option to surgery and radiation.

However, the study "fails to give a balanced view of the facts," said critic Allan Siperstein, MD, from the Department of Endocrine Surgery at the Cleveland Clinic.

"Everyone agrees that the incidence of thyroid cancer is increasing," Dr. Siperstein told Medscape Medical News. But he disagrees with the authors' contention that it is increasing solely because of increased detection (usually with a physical exam or imaging for other conditions).

"The paper also says that the death rate [from thyroid cancer] has been flat. That's not true," he noted.

This is an important criticism because the overdiagnosis argument hinges, in part, on the notion that the death rate is flat (indicating that mostly indolent tumors are being found with increased scrutiny).

Another critic also agrees that the study is imbalanced.

There is something else likely going on in the American population, said Raymon Grogan, MD, from the endocrine surgery group at the University of Chicago.

Increased detection resulting from commonplace imaging has "probably" resulted in some overdiagnosis in the United States, but that is only part of the story, he said.

Thyroid cancer is also increasing in parts of the world where imaging is uncommon, suggesting that other factors are driving the rising incidence all over the globe. "The incidence rates are increasing in China, Brazil, India, and other countries," said Dr. Grogan.

As for active surveillance, Dr. Grogan believes there is a basic problem. "We don't know who will have a bad cancer," he told Medscape Medical News. "If papillary thyroid cancer is diagnosed, we can't just let it sit there," he explained, because there are no prognostic tools that provide strong guidance on whether to treat or whether to watch and wait.

A Closer Look at Death Rates

Dr. Welch is arguably America's most high-profile researcher of cancer incidence, overdiagnosis, and overtreatment. He has published many studies on, among other things, prostate cancer incidence in the age of prostate-specific antigen testing and breast cancer incidence in the age of mammography.

In this study, Drs. Welch and Davies looked at trends in thyroid cancer from 1974 to 2009.

Using data from the Surveillance, Epidemiology, and End Results (SEER) program, they found that the incidence of thyroid cancer nearly tripled during the study period, from 4.9 per 100,000 in 1975 to 14.3 per 100,000 in 2009.

Using data from the National Vital Statistics System of the Centers for Disease Control and Prevention (CDC), they found that the mortality rate was "stable" (approximately 0.5 deaths per 100,000) during the same period.

This is a key finding, because the proportion of people dying from thyroid cancer would be expected to increase over time if there was an epidemic of clinically significant disease (and not just an epidemic of the diagnosis of indolent cases), Drs. Welch and Davies point out.

However, Dr. Siperstein said that their graph depicting mortality rate is misleading. It gives the impression of a flat rate because it is over such a long period of time (nearly 35 years).

Statistics from the past 10 years, he said, tell another story. They indicate that the death rate from thyroid disease is not flat; it is increasing faster than any other cancer except liver cancer.

Whereas Drs. Welch and Davies got their mortality data from the CDC, Dr. Siperstein pointed to a set of mortality data from the SEER program to illustrate his contention.

SEER data indicate that the death rate from thyroid cancer increased an average of 1.2% per year from 2001 to 2010. That is second only to liver cancer, which increased an average of 2.4% per year during that decade. This is in contrast to most major cancers, which saw a decrease — not an increase — in death rates during these years.

The increase in the death rate from thyroid cancer is evidence of a serious clinical issue, not just a case of overdiagnosis, suggested Dr. Siperstein.

But in an email to Medscape Medical News, Dr. Welch did not concede Dr. Siperstein's point. "I'm not sure whether this is a true 'signal' or 'noise'," he said about the more recent death rates. The death rate "has gone down and up a tiny bit," he said, noting that mortality was 0.55 per 100,000 in 1975 and 0.51 per 100,000 in 2010.

Another point of contention, Dr. Siperstein said, is the increase in the absolute number of larger tumors.

Drs. Welch and Davies report that the size distribution of detected thyroid cancers has shifted toward smaller lesions (≤1 cm), and larger lesions (>2 cm) are now a lower percentage of the total. This is evidence of overdiagnosis, they say.

But heightened diagnostic scrutiny alone does not fully explain the increase in large-sized thyroid cancers, said Dr. Siperstein.

He acknowledged that the percentage of smaller lesions increased from 25% in 1988/89 to 39% in 2008/09. And during the same period, the percentage of larger lesions decreased from 42% to 33%. But the absolute numbers, which were not reported in the study, indicate that both the smaller and larger lesions were increasing. This does not happen in a population in which a phenomenon such as screening causes, all by itself, an uptick of cancer detection. Something else is at work, he said.

Dr. Welch countered that "larger nonprogressive tumors may not have been diagnosed in the past, [but] now they are." Also, he said that although size is "certainly relevant to overdiagnosis," it is not "the whole story."

Active Surveillance and Other Ideas

"We believe the time has come to address the problem of papillary thyroid cancer overdiagnosis and overtreatment," write Drs. Welch and Davies in their conclusion.

This statement refers to their finding that "virtually the entire increase" in the incidence of thyroid is attributable to papillary thyroid cancer, an abnormality that is usually asymptomatic.

The authors argue that active surveillance is a "logical next step" for these patients. In both Japan and the United States, centers such as the Memorial Sloan-Kettering Cancer Center in New York City have initiated active surveillance studies.

However, Dr. Siperstein said that such an approach might not be appealing to thyroid cancer patients, who are usually in their 50s at diagnosis. "You may be asked to live with the disease for 30 to 40 years," he said. It is a different situation for prostate cancer, where active surveillance is used as a strategy because that is often diagnosed in elderly men who have a shorter life expectancy.

Drs. Welch and Davies also believe that clinicians should look at their thresholds for palpating, imaging, and biopsying the thyroid because these thresholds have "likely fallen too far."

Furthermore, to help rein in overtreatment and overdiagnosis, a reclassification of small thyroid neoplasms is in order. The word cancer should be dropped, they argue.

The study was funded by the Department of Veterans Affairs and the Dartmouth Institute for Health Policy and Clinical Practice. Dr. Welch and Dr. Davies have disclosed no relevant financial relationships.

JAMA Otolaryngol Head Neck Surg. Published online February 20, 2014. Abstract

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