New guidelines from the American Thyroid Association (ATA) offer wide-ranging recommendations on the extensive clinical challenges involved in the management of thyroid nodules and differentiated thyroid cancer (DTC), as rates of nodule detection soar and options for risk assessment for thyroid cancer become at once more advanced yet more complicated. For the first time, a medical oncologist was included among the authors of the guidelines.
"A major goal of these guidelines is to minimize potential harm from overtreatment in a majority of patients at low risk for disease-specific mortality and morbidity, while appropriately treating and monitoring those patients at higher risk," writes the ATA guidelines task force.
In compiling the new "ATA management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer," published online November 18 in Thyroid, the task force of experts conducted an exhaustive review of evidence to update recommendations to reflect the rapid advances in technology and science that have significantly transformed the field since the publication of the previous guidelines in 2009.
"The most notable aspect of the guidelines from my perspective is the extreme depth of coverage and level of detail and nuance included in discussions in support of each recommendation," Keith C Bible, MD, a task-force member and chair of the endocrine malignancies disease–oriented group at the Mayo Clinic Cancer Center, in Rochester, Minnesota, told Medscape Medical News.
"This guideline document is much more detailed and comprehensive than other available guidelines and provides practical clinical guidance for providers so as to encourage thoughtful and individualized patient care," he added.
In total, the guidelines include 101 recommendations, including some important changes from the 2009 guidelines as well as new sections altogether on issues including: the follow-up of patients with thyroid nodules who do not have a biopsy; molecular testing for patients with indeterminate cytology; assessing the risk for recurrence; management of voice and parathyroid issues around surgery; and the definition and management of radioiodine-refractory DTC.
First Time a Medical Oncologist Included in Task Force
The task force for the new guidelines is also the first to include a medical oncologist, helping with guidance on issues such as the use of kinase inhibitors for DTC, Dr Bible noted.
"[A lot of] new data have emerged related to the use of kinase inhibitors as therapeutics in progressive, metastatic, and symptomatic DTC patients," he explained. "The 2015/16 guidelines are considerably expanded and revised in this respect," with two kinase inhibitors, sorafenib [Nexavar, Bayer] and lenvatinib [Lenvima, Eisai], now approved in the United States and the European Union for use in DTC.
The guidelines specifically make a weak recommendation, based on moderate-quality evidence, that kinase-inhibitor therapy be considered in DTC patients who fail to respond to radioactive-iodine therapy or who have metastatic, rapidly progressive, symptomatic, or imminently threatening disease.
Another notable change in the guidelines is a shift in recommendations on the use of radioactive iodine in patients with thyroid cancer, which may spark some debate, Dr Bible said.
"The new guidelines present I think a more nuanced approach to the use of radioactive iodine," he explained.
"[There is a] move further away from recommending uniform use of radioactive iodine in all thyroid-cancer patients, leaving some proponents of radioactive-iodine therapy unhappy with the guidelines."
According to the new recommendations, radioactive-iodine remnant ablation after thyroidectomy is not routinely recommended for low-risk DTC patients or after lobectomy or total thyroidectomy for patients with unifocal or multifocal papillary microcarcinoma in the absence of other adverse features. The recommendation is classified as "weak," based on low-quality evidence.
Radioactive-iodine adjuvant therapy, meanwhile, "should be considered" after total thyroidectomy in DTC patients with intermediate risk and is routinely recommended after total thyroidectomy in patients at high risk, according to the guidelines. The recommendation is also classified as weak, based on low-quality evidence.
Guidance on Surgery for DTC, Management of Thyroid Nodules
Another key change is the recommendation that lobectomy or thyroidectomy are both reasonable surgical approaches for DTC 1 to 4 cm, a shift from 2009 guidelines, which recommended thyroidectomy for all nodules larger than 1 cm, explained Bryan R Haugen, MD, of the University of Colorado, Aurora, who led the task force.
Another recommendation, that thyroid nodules smaller than 1 cm do not need to be biopsied and that not all larger than 1 cm need to be biopsied, is the subject of debate, challenged in a study presented last month at the 2015 International Thyroid Congress and Annual Meeting of the American Thyroid Association (ITC/ATA).
In that study, which looked at nearly 1000 thyroid nodules, researchers found no significant difference in prognosis and disease recurrence between nodules that were smaller than 1 cm compared with those larger than 1 cm.
Factors that did show statistically significant association with the highest risk included extrathyroid extension, aggressive histology, positive surgical margins, and capsular or lymphovascular invasion.
Senior author Emad Kandil, MD, chief of the endocrine surgery section at Tulane University School of Medicine, in New Orleans, Louisiana, told Medscape Medical News that choosing not to cytologically evaluate smaller nodules, as is the new ATA recommendation, "may not be justified in the light of identical outcomes and disease recurrence risk as for larger nodules."
This is because "larger people will have larger thyroids and smaller people will have smaller thyroids, so we can't just focus on size of nodules," Dr Kandil explained. "The focus should be on molecular markers and not just the size."
Dr Haugen responded that the researchers' conclusion "is a reasonable caution" but noted that ATA advocates only omitting cytological evaluation with fine-needle aspiration"in those patients who have ultrasound features that do not indicate a concern, such as no abnormal lymph nodes and no ultrasound evidence of extrathyroid extension or tumor at the capsule of the thyroid gland." He also noted that Dr Kandil and colleagues "did not analyze for these features preoperatively."
Discovering the presence of a positive BRAF mutation is not turning out to be as predictive of risk as once thought, Dr Haugen said. "We are still cautioning that forgoing fine-needle aspiration in patients with sonographically suspicious nodules smaller than 1 cm should be done only in carefully selected patients."
Epidemic of Thyroid Cancer
Recommendations are likely to continue to evolve as detection rates of thyroid cancers rise, adding to the pressing need for more evidence to help guide clinical decision making, Dr Bible stressed.
"There is an 'epidemic' of papillary thyroid cancer noted worldwide, particularly in developed countries, apparently arising primarily due to increased detection of minute papillary cancers, either from intentional thyroid-cancer screening (for instance, in South Korea) or by incidental detection from the increasing use of medical imaging (for instance, in the United States)," he explained.
"Available data suggest that the vast majority of these micropapillary cancers would not have previously been recognized and furthermore suggest that most appear to be indolent and not requiring of aggressive therapy — but more evidence is required to define how to respond most appropriately."
Dr Haugen has received grant/research support from Veracyte and Genzyme, as well as a one-time speaker honorarium from Genzyme. Dr Bible has no relevant financial relationships. Disclosures for the coauthors are listed in the paper. Dr Kandil has no relevant financial relationships.
Thyroid. Published online November 18, 2015. Article