May 9, 2017 -- Citing the lack of evidence for
an overall benefit as well as the risk of harm from overdiagnosis and
overtreatment, the U.S. Preventive Services Task Force (USPSTF) has finalized
its recommendation against the use of screening with neck palpation or ultrasound
for thyroid cancer in low-risk, asymptomatic adults.
Updating its previous guidance from 1996, the
USPSTF gave thyroid cancer screening a D grade, which indicates the task force
believes there is moderate or high certainty that a medical service has no net
benefit or that the harms outweighs its benefits. The D grade kept to the task
force's draft
recommendation published in November.
Writing in a statement
published in the May 9 issue of the Journal of the
American Medical Association, Vol. 317:18, pp. 1882-1887), the
task force said it found inadequate evidence to estimate the accuracy of neck
palpation or ultrasound as a screening test for thyroid cancer in asymptomatic
people. It also pointed to a lack of adequate direct evidence that the
screening tests improved health outcomes
"However, the
USPSTF determined that the magnitude of benefit can be bounded as no greater
than small, based on the relative rarity of thyroid cancer, the apparent lack
of difference in outcomes between patients who are treated versus only
monitored (i.e., for the most common tumor types), and the observational
evidence demonstrating no change in mortality over time after introduction of a
population-based screening program," the task force wrote.
Furthermore, the task
force found inadequate direct evidence to assess the harm of screening for
thyroid cancer in asymptomatic adults. However, the "USPSTF found adequate
evidence to bound the magnitude of the overall harms of screening and treatment
as at least moderate, based on adequate evidence of serious harms of treatment
of thyroid cancer and evidence that overdiagnosis and overtreatment are likely
consequences of screening," the group wrote.
As a result, the
USPSTF said it concluded with moderate certainty that thyroid cancer screening
in asymptomatic adults results in harms that outweigh the benefits.
Review process
The USPSTF's decision
was based on an evidence report and systematic review prepared for the task
force by a team led by Dr. Jennifer Lin of Kaiser Permanente Center for
Health Research in Portland, OR. The group initially reviewed 707 full-text
articles from searches of Medline, PubMed, and the Cochrane Central Register of
Controlled Trials for relevant studies. The researchers then settled on 67 studies
for the final analysis. Two reviewers independently appraised the papers and
extracted study data from those they deemed to have fair-to-good quality (JAMA,
May 9, 2017, Vol. 317:18, pp. 1888-1903).
Lin and colleagues
found no studies that examined the benefit of thyroid cancer screening,
although two studies showed that neck palpation was not sensitive for detecting
thyroid nodules. The reviewers also noted that the combination of selected
high-risk sonographic features was specific for thyroid malignancy in two
methodologically limited studies.
As for harms, the
reviewers found that three studies directly addressed the harms of thyroid
cancer screening, but none suggested any serious harms from screening or
ultrasound-guided fine-needle aspiration. However, no screening studies
directly examined the risk for overdiagnosis, according to the group.
The researchers noted
that two observational studies included patient cohorts treated for
well-differentiated thyroid cancer as well as those with no surgery or
surveillance. However, these studies didn't adjust for confounding factors and
were therefore not designed to determine if patient outcome was improved by
earlier or immediate treatment, according to the researchers.
Regarding treatment
complications, the researchers found in 36 studies that the 95% confidence
interval was 2.12 to 5.93 cases of permanent hypothyroidism per 100
thyroidectomies and 0.99 to 2.13 cases of recurrent laryngeal nerve palsy per
100 operations. Also, the reviewers said they found in 16 studies that treating
differentiated thyroid cancer with radioactive iodine is associated with a
small increase in the risk of second primary malignancies and with a higher
risk of permanent adverse effects on the salivary gland, such as dry mouth.
"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 important patient health outcomes," the task force
concluded. "Screening that results in the identification of indolent
thyroid cancers, and treatment of these overdiagnosed cancers, may increase the
risk of patient harms."
Opinions vary
In an editorial
published online May 9 in JAMA:
Otolaryngology -- Head and Neck Surgery, Dr. Louise Davies
of the Veterans Affairs Medical Center in White River Junction, VT, and
Dr. Luc Morris from Memorial Sloan Kettering Cancer Center in New York
City said the USPSTF recommendation should discourage clinicians from screening
for thyroid cancer with neck palpation, ultrasonography, or other techniques.
They referred to the lack of evidence that detecting low-risk asymptomatic
papillary thyroid cancer leads to a better outcome than just detecting and
treating the cancer in symptomatic patients.
"In addition,
given the prevalence of thyroid nodules and the typically slow growth
trajectory of the most common form of thyroid cancer, screening programs will
be associated with a clinically significant amount of harm," they wrote.
"It is hoped that these recommendations will provide support in the United
States for the development of monitoring programs for adults with small,
incidentally identified cancers, with the ultimate goal of avoiding unnecessary
treatments."
But perhaps
overdiagnosis isn't to blame for the higher number of thyroid cancer diagnoses.
In an editorial published online May 9 in JAMA Surgery,
a team led by Dr. Julie Ann Sosa of Duke University Medical Center pointed
to recent research that found an increase in overall thyroid cancer incidence
over the past three decades, including higher incidence and mortality rates for
advanced-stage papillary thyroid cancer.
What's more, overall
incidence-based mortality also grew from 1994 to 2013 -- particularly for
patients diagnosed with advanced-stage papillary thyroid cancer. These findings
are consistent with a true increase in thyroid cancer occurrence in the U.S.,
and challenge the prevailing hypothesis that overdiagnosis is the sole culprit
for this changing epidemiology, according to the group.
"These results
suggest that a new focus should be placed on understanding alternative
explanations for this increase other than overdiagnosis, including potentially
modifiable factors, such as obesity and environmental exposures outside of the
known influence of radiation," they wrote. "Furthermore, it would
seem that additional energies and resources should be focused on supporting
innovation and discovery around the management of locally advanced and
metastatic thyroid cancer."
Nonetheless, the
USPSTF recommendation may represent an opportunity to pause and recalibrate the
collective approach to thyroid cancer screening, diagnosis, management, and
surveillance, according to Sosa and colleagues.
"If the
explanation for the rise in thyroid cancer is, indeed, not just overdiagnosis,
and if mortality from thyroid cancer is also increasing, then enthusiasm for
this (non)screening recommendation should be more muted," they wrote.
"For clinicians and scientists working in the field of thyroidology, this
is an interesting and compelling time. Clearly, more research is needed to
identify alternative causes for the increasing incidence of the disease, to
inform efforts at prevention, and to develop novel approaches to the management
of advanced thyroid cancer."
Indeed, what the field
needs is a noninvasive measure -- either radiographic or by biomarker -- to
distinguish between nodules that have thyroid cells that will leave the capsule
and cause morbidity and those that will not, said Dr. Anne Cappola of the
University of Pennsylvania in an accompanying editorial in JAMA (May
9, 2017, Vol. 317:18, pp. 1840-1841).
"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 wrote. "New technologies are
required."
