THYROID CANCER OVERDIAGNOSIS

A large fraction of thyroid cancer cases represent overdiagnoses, and at least half a million patients, most of them women, may have received unnecessary surgery and other cancer treatments, say researchers from the the International Agency for Research on Cancer (IARC), in Lyons, France.

Their warning about an epidemic of thyroid cancer overdiagnosis comes from an analysis of cancer registry data from 12 countries published August 17 in the New England Journal of Medicine .

Salvatore Vaccarella, PhD, and colleagues at the IARC estimate that more than 470,000 women and 90,000 men may have ben overdiagnosed with thyroid cancer in 12 "high-income" countries (Australia, Denmark, England, Finland, France, Italy, Japan, Norway, Republic of Korea, Scotland, Sweden, and the United States) from 1987 to 2007.

Most of these thyroid cancers were small, low-risk papillary carcinomas, they note. The "vast majority" of these patients underwent total thyroidectomy, and a "high proportion" also received neck lymph-node dissection and radiotherapy, but these interventions do not have "proven benefits in terms of improved survival," the researchers point out.

"We don't know whether this trend has continued, since post-2007 data were not available," the researchers comment. "However, if we take the most recent available period, 2003 - 2007, as typical of current practice, we estimate that overdiagnosis in women accounts for 90% of thyroid-cancer cases in South Korea; 70 to 80% in the United States, Italy, France, and Australia; and 50% in Japan, the Nordic countries, and England and Scotland."

The overdiagnosis is blamed on increasing medical surveillance and the introduction of new diagnostic techniques, such as neck ultrasonography (since the 1980s) and, more recently, CT scanning and MRI. This new technology has led to the detection of a large number of indolent, nonlethal diseases that exist in abundance in the thyroid gland of healthy people of any age, the researchers comment, adding that most of these tumors are very unlikely to cause symptoms or death.

"Countries such as the USA, Italy, and France have been most severely affected by overdiagnosis of thyroid cancer since the 1980s, after the introduction of ultrasonography, but the most recent and striking example is the Republic of Korea," Dr Vaccarella commented in a statement. "A few years after ultrasonography of the thyroid gland started being widely offered in the framework of a population-based multicancer screening, thyroid cancer has become the most commonly diagnosed cancer in women in the Republic of Korea, with approximately 90% of cases in 2003 - 2007 estimated to be due to over diagnosis."

IARC Director Christopher Wild, PhD, added: "The drastic increase in overdiagnosis and overtreatment of thyroid cancer is already a serious public health concern in many high-income countries, with worrying signs of the same trend in low- and middle-income countries. It is therefore critical to have more research evidence in order to evaluate the best approach to address the epidemic of thyroid cancer and to avoid unnecessary harm to patients.

Epidemic of Medical Testing

"These are striking results," says Luc G. T. Morris, MD, from the Head and Neck Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York City, who was approached for comment. "It is fair to say that the large number of thyroid cancers being diagnosed represent an epidemic of diagnosis, or an epidemic of medical testing, rather than an epidemic of true disease."

Dr Morris commented that the researchers used "an elegant model" to conclude that 70% to 90% of thyroid cancers diagnosed in the United States, Western Europe, and Australia were identified incidentally. In the past, these cancers were clinically occult and were never detected, he pointed out. "These excess diagnoses of cancer are very likely to be overdiagnosed cancers," he told Medscape Medical News.

These results also mean that most patients are receiving treatment that does not benefit them and that subjects them to risks of injury to the voice, permanent hypoparathyroidism, as well as the attendant risks of radioactive iodine treatment, he pointed out.

"Fortunately the thyroid cancer field has begun to accept that overdiagnosis is a very real phenomenon in thyroid cancer," Dr Morris added

Consider Watchful Waiting

The discrepancy between incidence and mortality is much higher for thyroid cancer than it is for cancer of the breast, cervix, or prostate, Dr Vaccarella noted in an interview.

This appears to be particularly true for female patients with thyroid cancer who are 15 to 49 years of age. In this group, the incidence-to-mortality ratio is higher than 300, whereas in patients of the same age with breast cancer, the corresponding ratio is "lower than 10," Dr Vaccarella told Medscape Medical News. 

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Studies from Japan suggest that immediate surgery and watchful waiting are equally effective in preventing mortality, Dr Vaccarella said. One study showed that of 1235 patients with papillary microcarcinomas, only 3.5% experienced clinical progression of disease during a 75-month follow-up, and there were no deaths.

Low-risk tumors should be monitored and reclassified using terms other than cancer, as has been done previously for cervical precancer, he suggested.

"For decades, our colleagues in Japan have been offering active surveillance as an alternative to surgery for patients with small thyroid cancers," Dr Morris noted. "Their results are fully in line with what would be suggested by these data — that the vast majority of small thyroid cancers do not grow or progress under close observation and do not require treatment."

Also approached for comment, Hassan Arshad, MD, assistant professor in the Department of Head and Neck Surgery/Plastic and Reconstructive Surgery at Roswell Park Cancer Institute, Buffalo, New York, said that "more research needs to be done" to determine which patients will be well served by a watch-and-wait vs a surgical approach.

Until then, he recommends that clinicians make sure patients are fully aware of treatment options, the natural history of small carcinomas, and the risks of overly aggressive treatment.

At Memorial Sloan Kettering Cancer Center, active surveillance has been offered to patients with low-risk, small, intrathyroidal cancers for several years, Dr Morris said. "Our results have mirrored the Japanese results, and fewer than 5% of patients end up showing any signs of tumor growth under close observation," he said.

"We believe this personalized or risk-adjusted approach is the best treatment for overdiagnosed thyroid cancers, and now that the ATA [Amerian Thyroid Association] guidelines support such an approach, we hope that more patients in these countries will be offered this treatment strategy."

Overdiagnosis Is a Problem

"Clearly, overdiagnosis of thyroid cancers is playing a large role in the rising incidence of thyroid cancers seen in this country and worldwide," Dr Arshad said. "What is also increasingly becoming evident is that we are probably doing more surgery than necessary in response to this overdiagnosis."

The recommendation that certain types of papillary thyroid cancer be reclassified as a benign neoplasm is evidence of this, he noted.

Last spring, an international panel of pathologists and clinicians renamed encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) to reflect the fact that it is noninvasive and has a low risk for recurrence.

The research that led up to this reclassification was published online April 14 in JAMA Oncology.

Similarly, the ATA recently issued updated guidelines stating that thyroid lobectomy is an acceptable treatment — in lieu of total thyroidectomy — for selected well-differentiated thyroid carcinomas. "Following ATA guidelines regarding when to biopsy thyroid nodules may also help limit overdiagnosis," Dr Arshad told Medscape Medical News.

The authors of the article, Dr Arshad, and Dr Morris have disclosed no relevant financial relationships.

N Engl J Med. 2016;375:614-617. Abstract