In 2016, the American Thyroid Association (ATA) published its latest update on management guidelines of thyroid nodules and thyroid cancer (Thyroid. 26:1–133). The guidelines came nearly seven years after the previous update in 2009 (Thyroid. 19:1167–1214). Experts interviewed for this article shared how these guidelines changed patient care. Among the changes they cited are less aggressive detection of thyroid nodules, use of molecular diagnostics to further evaluate biopsies, hemithyroidectomy for low-risk thyroid cancer, pre-operative assessment of the voice and larynx, an increase in the threshold for delivering radioactive iodine for thyroid cancer, and active surveillance in select patients with small thyroid cancers.
“The guidelines had a profound impact on clinical practice that spanned the entire breadth of how we assess and manage patients with thyroid nodules and thyroid cancer,” said David Terris, MD, Regents’ Professor of otolaryngology and endocrinology at Augusta University in Georgia and surgical director of the Augusta University Thyroid and Parathyroid Center.
Detection and Diagnosis of Thyroid Nodules
One key area of change in the guidelines is the recommendation for less aggressive detection efforts. Dr. Terris pointed to evidence showing that much of this increase is due to overly aggressive detection efforts that have led to identification of biologically unimportant nodules and even micro-cancers that probably don’t need treatment (Endocr Pract. 2015;21:686-696). He cited, for example, the rapid increase in thyroid cancers detected over the past decade, particularly in South Korea, where diagnosis of thyroid cancer increased nine-fold (Endocr Pract. 2015;21:686-696). Prior to the 2015 guidelines, nodules 10 mm or greater were recommended for biopsy, and if the biopsy indicated cancer or was indeterminate, then surgery was performed, Dr. Terris explained. The 2015 guidelines changed this threshold. “Now the bar is 20 mm unless the nodule looks really concerning, so we’ve doubled the size of the nodule for which we would consider a biopsy,” he said.
A second important change endorsed by the 2015 guidelines, he said, is the use of molecular diagnostics to augment the information obtained when biopsies are performed. “For many years there were basically three results you could get with a biopsy—cancer, benign, or indeterminate. The indeterminate category represented about 30%-40% of biopsies, and most of these patients ended up undergoing surgery when many probably didn’t need it,” he said.
With molecular diagnostics, he said, clinicians can further differentiate the indeterminate nodules. “More than 50% of these nodules will have a molecular fingerprint strongly suggesting that they are benign,” he said. “So we’ve been able to avoid surgery on a bunch of the patients in the indeterminate category.”
David L. Steward, MD, director of head and neck surgery, endocrine surgery, and clinical research at the University of Cincinnati College of Medicine, said the 2015 guidelines also had an impact on the use of ultrasound to help guide management of indeterminate nodules. “The latest 2015 guidelines resulted in much more selective fine-needle biopsy of thyroid nodules based more on sonographic pattern and risk of malignancy rather than just size alone,” he said.
Dr. Steward highlighted the importance of this impact on clinical practice given the increasing number of incidental nodules detected through imaging. Further, he said that cytopathological classification using the Bethesda system (Thyroid. 2009;19:1167-1214), has improved consensus in reporting of results but has resulted in another problem. “Cytologically indeterminate nodules (Bethesda III and IV) are increasingly common, and this is a problem that patients and clinicians face,” he said, explaining that 20%-30% of these are at risk of being malignant.
Maisie Shindo, MD, professor of otolaryngology–head and neck surgery at Oregon Health & Science University School of Medicine in Portland, agreed that the 2015 guidelines helped to determine which nodules to biopsy and how to further categorize biopsied nodules through molecular diagnostics. But she emphasized that the use of molecular diagnostics was still relatively new when the guidelines were published, so the recommendations on its use weren’t specific. “The guideline recommended you can incorporate molecular markers in the decision making,” she said. “If molecular testing is going to be used, patients should be counseled regarding the potential benefits and limitations of the testing and about possible uncertainties in the therapeutic and long-term clinical implications of the results.”
The 2015 guidelines recommended some key changes to surgical treatment of thyroid nodules. One primary change was the recommendation for hemithyroidectomy for low-risk thyroid cancer instead of a more aggressive total thyroidectomy and elective central node dissection for these cancers. “Prior to the 2015 guidelines, if a patient had a cancer 10 mm or more, he or she got a total thyroidectomy,” said Dr. Terris.“Now you can have only a hemithyroidectomy for cancers up to 40 mm, and that is clinically important because we’re saving many patients from the risk of significant harm.”
Dr. Shindo also highlighted the significant changes in the new 2015 guidelines with regard to the extent of surgery for thyroid cancer, saying that the guidelines state that hemithyroidectomy alone may be sufficient initial treatment for low-risk papillary and follicular carcinoma in cancer between 1 and 4 cm in the absence of lymph node metastasis. But she also said that one of the limitations of the guideline was that it did not emphasize the need to correlate ultrasound images with the clinical picture to ensure an accurate assessment.
“For example, if a clinician doesn’t review the ultrasound images, they may miss an extra thyroid extension or some of the other aggressive-looking features and decide on a conservative surgical approach,” she said. “In order to take a conservative approach with surgery, or even doing the biopsy, it requires that the clinician looks at the imaging studies.”
If molecular testing is going to be used, patients should be counseled regarding the potential benefits and limitations of the testing and about possible uncertainties in the therapeutic and long-term clinical implications of the results. —Maisie Shindo, MD
Failure to correlate the imaging findings with the clinical picture could lead to undertreating or overtreating the patient, she said.
Dr. Steward emphasized that using a more conservative surgical approach of lobectomy versus total thyroidectomy preserves the vulnerable structures around the thyroid gland: the laryngeal nerves and parathyroid glands. “This has the goal of reducing patient morbidity and complications from overtreatment of cancers that have very low risk of mortality,” he said.
Greg Randolph, MD, professor of otolaryngology-head and neck surgery and the Claire and John Bertucci Endowed Chair in thyroid surgical oncology at Harvard Medical School in Boston, highlighted a number of recommendations in the 2015 ATA guideline that have had a significant impact on practice, particularly for stressing the important role of otolaryngologists in the management of thyroid cancer.
For example, he described ATA guideline Recommendation 40, which states that all patients who undergo thyroid surgery should have their voice evaluated prior to surgery. “If a patient presents with a voice abnormality, that is an important finding that may suggest a cancer extending outside the thyroid gland and invading into the recurrent laryngeal nerve,” he said.
He also highlighted Recommendation 41, which states the need for a preoperative laryngeal exam (in addition to voice evaluation) in all patients with a voice abnormality, with a history of surgery of the neck or chest that could have injured the vagus or laryngeal nerve, or with evidence of extrathyroid extension or significant central neck nodal metastases. “In these three circumstances, you need to exam the larynx prior to surgery,” he said.
All of these recommendations, he said, were incorporated into the ATA 2015 guidelines based on evidence first published in the Clinical Practice Guidelines: Improving Voice Outcomes After Thyroid Surgery by the American Academy of Otolaryngology–Head and Neck Surgery in 2013 (Otolaryngol Head Neck Surg. 2013;148(6 Suppl):S1-37).
The guidelines had a profound impact on clinical practice that spanned the entire breadth of how we assess and manage patients with thyroid nodules and thyroid cancer. —David Terris, MD
“These specific recommendations linked to voice and larynx are very important to otolaryngologists because we are the specialty that are able to examine the larynx, assess voice, and know about the larynx and its innerva-
tion”, he said. “Inclusion of these recommendations that focus on the larynx and voice indicates the importance of the otolaryngologist in the evaluation and management of these patients.”
Along with these changes in surgery, other changes to treatment include the use of radioactive iodine. Rather than using it in everyone who undergoes a total thyroidectomy, as has been the standard approach for many years, the 2015 guidelines recommend increasing the threshold for delivering radioactive iodine for thyroid cancer. “If a thyroid cancer has been judged to be low risk, we don’t feel as obligated to obsess over the thyroglobulin anymore and therefore don’t need to give all these patients radioactive iodine,” said Dr. Terris. “This reduces side effects, as well as cancer itself, from the radiation, so we’re doing patients a favor by avoiding treatment with radioactive iodine.”
One other change to practice suggested in the 2015 guideline is the potential for patients with small thyroid cancers that have not spread outside the gland, especially older patients, to undergo active surveillance. “The recognition that these older patients with small cancers may not need any treatment as long as they are getting active surveillance is new,” said Dr. Steward, citing evidence emerging from Japan over the past 10 years.
“This is not widely accepted in the 2015 guidelines, but will be more highlighted in the upcoming guideline,” he said.
Upcoming Updated Guideline
The ATA is working on its next iteration of the guidelines. According to Lisa Orloff, MD, director of endocrine head and neck surgery at Stanford University School of Medicine, director of the Stanford Thyroid Tumor Program at the Stanford Cancer Center in Stanford, Calif., and co-chair of the guideline, the upcoming updated guideline will be split into two separate documents: one focusing on the management of benign thyroid nodules and the other focusing on the management of differentiated thyroid cancer. “Both documents will have new information on diagnostic categories such as noninvasive follicular thyroid neoplasm with papillary-like nuclear features, nonsurgical alternatives to management, and new evidence on outcomes,” she said. “The discussion of molecular testing of thyroid nodules will be much more detailed as genetic tests and information have evolved, and recommendations for surgical decision-making and variations [on] and alternatives to surgery will also be expanded.”
The estimated target date for completion is December 2020.
Mary Beth Nierengarten is a freelance medical writer based in Minnesota.