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Task force recommends against thyroid cancer screening in asymptomatic adults
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The U.S. Preventive Services Task Force today issued a final recommendation against screening for thyroid cancer in adults who have no signs or symptoms of the disease.
The D recommendation — the same grade the United States Preventive Services Task Force (USPSTF) issued for thyroid cancer screening in 1996 — indicates there is moderate or high certainty that screening has no net benefit or that the harms of screening outweigh the benefits.
“Our evidence review suggested that thyroid cancer is rare in the United States and there were very few benefits to screening adults with no symptoms or signs,” task force member Karina W. Davidson, PhD, MASc, professor of medicine and psychiatry and director of the Center for Behavioral Cardiovascular Health at Columbia University Medical Center, told HemOnc Today. “We did find in our review serious harms associated with surgery, particularly for those who had small tumors, and for these reasons we are advising against screening patients with no symptoms or signs.”
The incidence of thyroid cancer detection has increased by 4.5% per year over the last 10 years — from 4.9 cases per 100,000 individuals in 1975 to 15.3 cases per 100,000 in 2013 — faster than for any other cancer.
SEER data indicate an estimated 637,115 individuals in the United States had thyroid cancer in 2013 and an estimated 56,870 new cases of thyroid cancer will be diagnosed in 2017, representing 3.4% of all new cancer cases in the country.
Despite the increased incidence, the thyroid cancer mortality rate has remained relatively unchanged. Five-year OS for is 98.1% overall, varying from 99.9% for localized disease to 55.3% for distant disease.
“We have no direct evidence to determine the rate of overdiagnosis that may be occurring in the United States, but we have indirect evidence that we have an increasing rate of detection of thyroid cancer,” Davidson said. “Even though most of those are treated, we don’t have a change in longevity and that can speak indirectly to the possibility of overdiagnosis.”
In adults without symptoms or signs of thyroid cancer, most lesions are benign and slow growing and will not affect the health of the individual during his or her lifetime, Davidson said.
“Yet, once told that someone has cancer, the immediate impulse is to assume that surgery or treatment is the best way of dealing with it,” Davidson said. “It is hard for people to understand that screening can sometimes be a bad thing but, in this case, it is leading to harms from surgery and we do not see that it is benefitting longevity or quality of life.”
Screening-associated harms
To update its 1996 recommendation, the USPSTF commissioned a systematic evidence review to examine the benefits and harms of screening for thyroid cancer in asymptomatic adults. The task force also assessed the diagnostic accuracy of screening — including through neck palpation and ultrasound — and the benefits and harms of treatment of screen-detected thyroid cancer.
In the systematic review conducted for the USPSTF, Jennifer S. Lin, MD, MCR, director of Evidence-based Practice Center at Kaiser Permanente Center for Health Research, and colleagues reviewed evidence from 67 studies published from 1966 to January 2016.
Researchers found inadequate evidence to estimate the accuracy of neck palpation or ultrasound as a screening test for thyroid cancer in asymptomatic persons.
Based on 36 fair-quality studies (n = 43,295) that reported on harms associated with thyroid surgery and radioactive iodine therapy, researchers found the rate of permanent hypoparathyroidism varied widely, from 2.12 to 5.93 events per 100 thyroidectomies. Researchers estimated a rate of 0.99 to 2.13 events per 100 surgeries — with or without lymph node dissection — for permanent recurrent laryngeal nerve palsy.
“Once you’ve been screened and told you have something that might be cancer, the trajectory toward either radiation or surgery is highly likely,” Davidson said. “Harms can include damage to the nerves that control speaking and damage to the parathyroid gland functions, along with hypoparathyroidism.”
Based on 16 studies (n = 291,796), treatment of differentiated thyroid cancer with radioactive iodine increased risk for permanent adverse effects on the salivary gland, such as dry mouth, and slightly increased risk for second primary malignancies.
Lin and colleagues concluded that, although ultrasonography of the neck using high-risk sonographic characteristics plus follow-up cytology from fine-needle aspiration can identify thyroid cancers, it is unclear if population-based or targeted screening can decrease mortality rates or improve patient health outcomes.
“The bottom line is we don’t have trials or well-designed observational studies to support screening for thyroid cancer,” Lin told HemOnc Today. “Studies using SEER data suggest that if you are diagnosed with papillary thyroid cancer in the United States, you almost certainly will be treated, meaning having your thyroid or part of your thyroid removed.
“Although thyroidectomies are generally safe, they are not without potential complications,” Lin added. “The biggest problem is that we don’t yet have a good way to determine which papillary thyroid cancers need to be treated; that is, which of these cancers will actually cause harm to the patient. Survival data from SEER, ecological data and autopsy data suggest that many papillary thyroid cancers don't need to be treated.”
The USPSTF’s recommendation against screening does not apply to individuals with hoarseness, pain, difficulty swallowing or other throat symptoms, or those who have lumps, swelling, asymmetry of the neck or other reasons for examination. It also does not apply to individuals at increased risk for thyroid cancer because of a history of exposure to ionizing radiation (medical treatment or radiation fallout), diets low in iodine, an inherited genetic syndrome associated with thyroid cancer, or a first-degree relative with a history of thyroid cancer.
“Certainly, for people who have a personal childhood history of irradiation or a family history of thyroid cancer, they may want to speak to their clinician about individualizing the decision to be screened,” Davidson said.
Accuracy, effectiveness of screening
The task force cited a prospective study conducted by Finnish researchers in which 5.1% of randomly selected adults had abnormal findings (thyroid nodule or diffuse enlargement) on neck examination. Researchers reported a sensitivity to detect thyroid nodules of 11.6% (95% CI, 5.1-21.6) and specificity of 97.3% (95% CI, 93.8-99.1).
One fair-quality retrospective observational study using 1973 to 2005 SEER data compared survival rates of persons treated (n = 35,663) vs. not treated (n = 440) for papillary thyroid cancer. Results showed that untreated individuals had a slightly worse 20-year survival rate than treated patients (97% vs. 99%; P < .001). However, researchers did not adjust for potential confounding despite statistically significant baseline differences between the two groups.
“Given the very real concern about overdiagnosis and subsequent overtreatment, it is important to conduct screening trials or good quality observational studies in populations at risk for thyroid cancer,” Lin said. “We also need trials or well-designed observational studies of early treatment vs. surveillance of papillary thyroid cancers. Most importantly, we need research to identify and vet prognostic indicators — either tumor makers or patient risk predictors — that can predict indolent aggressive vs. indolent thyroid cancer.”
There is a “research gap” in the area of active surveillance, Davidson said.
“We do not have evidence to suggest that watchful waiting is appropriate, and we do not have evidence that we can differentiate the small-growing tumors from those that are dangerous,” Davidson said. “Clearly, research is needed on both of those areas to help us guide oncologists about the appropriate treatments. We can suggest that any ways to reduce unnecessary radiation to the neck and throat is one way to prevent thyroid cancer. We have no recommendation at this point for patients who have symptoms or signs of thyroid cancer. We need more research for those patients to know what is the best course of treatment for them.”
There is a lack of knowledge about the differences between a thyroid cancer that never leaves the capsule of its nodule and a thyroid cancer that does, either through local extension or distant metastasis, Anne R. Cappola, MD, ScM, professor of medicine in the division of endocrinology, diabetes and metabolism at Perelman School of Medicine at University of Pennsylvania, wrote in an accompanying editorial.
“The prognosis of each thyroid nodule, prior to surgical excision, is needed,” Cappola wrote. “... Perhaps the difference between thyroid nodules that require surgery and those that do not involves the characteristics of the patient, not the characteristics of the nodule. Perhaps the difference is in immune surveillance or some other aspect of the patient, and one patient can keep the thyroid cancer contained to the nodule and another cannot.
“Using the same tools — palpation, ultrasound imaging and findings on microscopic examination — is unlikely to result in a different conclusion about screening for thyroid cancer in the future,” Cappola added. “New technologies are required.” – by Chuck Gormley
References:
Cappola AR. JAMA. 2017;317:1840-1841.
Lin JS, et al. JAMA. 2017;doi:10.1001/jama.2017.0562.
USPSTF. JAMA. 2017:doi:10.1001/jama.2017.4011.
For more information:
Karina W. Davidson, PhD, MASc , can be reached newsroom@uspstf.net.
Jennifer S. Lin, MD, MCR, can be reached at Kaiser Permanente Center for Health Research, 3800 N. Interstate Ave., Portland OR 97227-1098; email: jennifer.s.lin@kpchr.ortg.
Disclosure: The researchers report no relevant financial disclosures. Cappola reports no relevant financial disclosures.
Perspective
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Christopher Fundakowski, MD
The U.S. Preventive Services Task Force (USPSTF) recommended against screening for thyroid cancer in asymptomatic adults. USPSTF recommendations aim to be evidence based, and to focus on several key features of thyroid cancer:1. Thyroid cancer is relatively rare, with 15.3 cases occurring per 100,000 persons;
2. Thyroid cancer incidence is increasing at 4.5% per year, but survival is relatively stable; and
3. Five-year OS is very good at 98%.
Screening largely consists of physical examination and neck ultrasound, which alone are not considered harmful, but the potential risk for overdiagnosis and overtreatment may be substantial when applied on a population scale. No study has directly compared patient outcomes between screened and unscreened populations. Interestingly, prospective investigations in Japan that compared immediate surgery with active surveillance for papillary microcarcinoma showed that, over 4- to 6-year follow-up, no patients in the surveillance groups died of thyroid cancer. Unfortunately, as with many other investigations, these trials also are limited by lack of adjustment for confounding factors.
Potential harms from screening and treatment, although uncommon, are those related to biopsy and operative complications, such as hematoma, hypoparathyroidism, nerve injury and surgical mortality. It is important to note that this USPSTF recommendation is only intended for asymptomatic patients and should not discourage health care providers from evaluating patient complaints (eg, swallowing difficulty, hoarseness), or abnormal exam findings (eg, neck mass, thyroid nodule). Patients with high-risk clinical or family history, or those with physical exam findings, should be worked up appropriately, as this recommendation would not apply.
Although health care providers must be familiar with the available evidence, we must remember that each patient encounter is unique and clinical judgment remains of utmost importance.
Perspective
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Megan R. Haymart, MD
The U.S. Preventive Services Task Force recommendation against screening for thyroid cancer in adults without signs or symptoms of the disease is an appropriate and timely recommendation. As demonstrated in South Korea, screening for thyroid cancer will lead to more detection of disease. However, on thorough autopsy studies, close to one-third of adults who die of other causes have small thyroid cancers. For most adults, these small thyroid cancers never go on to cause harm.
Yet, treatment of thyroid cancer is associated with surgical risks — including permanent voice changes and low calcium — and with risks from radioactive iodine, including salivary gland damage and lacrimal duct damage. Most patients with thyroid cancer have relatively indolent disease and although there are a small proportion of thyroid cancer patients with aggressive and deadly disease, there is no evidence that screening the population at large improves outcomes for this small subset of thyroid cancer patients.
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