During the past 2 decades, Endocrine Today has reported on the latest developments in treating thyroid cancer. For its 20th year, the publication is taking a look back.

Twenty years ago, the options for treating differentiated thyroid cancer were much more limited than they are today.

When differentiated thyroid cancer was diagnosed 2 decades ago, most patients underwent a total thyroidectomy followed by radioactive iodine, regardless of the characteristics of the thyroid tumor or the patient.

Elizabeth H. Holt

“In the past, pretty routinely once we had a biopsy that came back indicative of cancer or looking like it could be a cancer, very often those patients would get the entire thyroid taken out,” Elizabeth H. Holt, MD, PhD, associate professor of endocrinology at Yale School of Medicine, told Healio.

Today, the treatment of thyroid cancer has been significantly altered. Advances in ultrasound neck mapping and molecular testing, in addition to updated risk stratification guidelines published by the American Thyroid Association in 2015, allow providers to take a more individual approach to managing thyroid cancer. This has led to less aggressive treatment for people with low-risk cancers.

“In the past, we sent every patient for total thyroidectomy plus radioactive iodine,” Arti Bhan, MD, FACE, division head of endocrinology at Henry Ford Health System, told Healio. “Risk stratification in differentiated thyroid cancer has changed and we now use information at the time of diagnosis and dynamic risk assessment during follow up, to determine extent of treatment.”

Other advances, such as molecular testing, have allowed even more individualized care in recent years. Elizabeth N. Pearce, MD, MSc, professor of medicine in the section of endocrinology, diabetes and nutrition at Boston University School of Medicine and an Endocrine Today Editorial Board Member, said providers better understand molecular drivers now than they did 20 years ago and can use this knowledge to prescribe treatment targeting specific mutations, particularly for people with more advanced cancer.

Despite these advancements, disparities exist in thyroid cancer treatment. Multiple studies have noted that Black adults have significantly fewer age-adjusted cases of thyroid cancer compared with white adults, but study results published in World Journal of Surgical Oncology in 2018 found that Black Americans had a 12% worse thyroid cancer survival rate compared with white Americans. Geography is also an issue, as a higher proportion of people treated by a low-volume surgeon have worse postoperative outcomes, according to study findings published in JAMA Otolaryngology – Head & Neck Surgery in 2016.

“Having access to a high-volume, experienced thyroid surgeon is critically important for the care of thyroid cancer patients,” Pearce told Healio.

Risk stratification changes treatment paradigm

In 2015, the ATA’s updated its guideline on thyroid cancer treatment outlined steps for risk stratification of patients with differentiated thyroid cancer and gave providers an important new tool when planning treatment. Although total thyroidectomy and radioactive iodine were commonplace for all patients with malignant thyroid cancer at the turn of the 21st century, the 2015 update, which were an update of the ATA’s original risk stratification guidelines published in 2009, advised health care professionals to categorize patients into low-, intermediate- or high-risk categories to construct a better treatment plan.

“By and large, low-risk patients don’t get recommended for radioactive iodine, even in cases where there may be small metastases in the lymph node of the central neck,” Holt, who is also and an Endocrine Today Editorial Board Member, said. “Triaging patients into those groups and using that information to inform whether to recommend radioactive iodine has been better standardized since 2015.”

Some people categorized with low-risk cancer may not have surgery or treatment immediately after risk stratification. Bhan noted that the guideline pushed providers more often toward monitoring low-risk patients.

Arti Bhan

“There’s a big movement toward active surveillance,” Bhan, who is also and an Endocrine Today Editorial Board Member, said. “In the peri-diagnostic period, if the cancer is categorized as very low risk, the choices range from careful monitoring or minimalistic surgical intervention. If the size of the tumor hasn’t changed, let’s watch these people over time.”

For those who undergo surgery, a total thyroidectomy is not necessarily a given. Neck mapping ultrasound gives providers a better idea of any local thyroid cancer progression and helps determine the extent of surgery needed.

“This helps us to know if there’s any disease in the lymph nodes in the lateral neck,” Holt said. “In the past, it wasn’t routine that everyone would get that screening. That helps to plan the surgery and tells us whether they need more extensive surgery.”

Molecular testing helps solve indeterminate nodules

Fine-needle aspiration is used to determine malignancy of thyroid nodules for most adults. However, about 15% of nodules are found to be cytologically indeterminate after the procedure. In the past, those with indeterminate nodules would have undergone diagnostic thyroid lobectomy to determine malignancy. The need for that has been greatly reduced with the advent of molecular testing, a process that identifies genomic or gene expression changes in thyroid biopsy samples.

“Using a combination of mutations and RNA expression changes, they are able to identify the risk of the patient based on a molecular profile,” Holt said. “They can tell you that this is a 3% risk for cancer, which is comparable to the risk you would get with a benign biopsy on cytopathology, or they might tell you there’s a 70% to 80% risk this is a cancer. That helps to determine who needs to go to surgery and who can be monitored with serial ultrasound.”

Using molecular testing to determine malignancy risk has helped to reduce the number of patients undergoing surgery. Holt noted that before molecular testing,  most patients with cytologically indeterminate nodules who underwent diagnostic lobectomy ultimately were found to have benign surgical pathology and therefore had not needed surgery.

Molecular testing also plays a role in monitoring some patients after thyroidectomy, according to Bhan.

“If the patient has a high-risk mutational profile, particularly mutational combinations associated with higher risk of recurrence, then it is reasonable to consider more careful follow-up or more aggressive therapy,” Bhan said. “Molecular testing can also be used for patients with radioactive iodine refractory cancer metastatic disease, to guide choice of therapy.”

Understanding cancer mutations has also improved the prognosis for those with anaplastic thyroid cancer, a rarer but much more aggressive form of cancer compared with differentiated thyroid cancer. According to study data published in JAMA Oncology in 2020, the median overall survival rate of anaplastic thyroid cancer for those diagnosed from 2000 to 2013 was 35% 1 year after diagnosis. That rate increased to 47% for those diagnosed from 2014 to 2016 and to 59% for those diagnosed from 2017 to 2019.

Elizabeth N. Pearce

“Very recently, with the advent of some of these targeted therapies for specific mutations, knowing the mutation that drives the anaplastic cancer has allowed for at least some patients to receive systemic therapies to provide a meaningful prolongation of life,” Pearce said. “That is, in itself, huge.”

Disparities in access to care

With these advancements in management, mortality rates for thyroid cancer have remained flat to very modestly elevated in recent years even as incidences of thyroid cancer continue to increase globally. However, some populations remain vulnerable, particularly those without access to an experienced surgeon.

“People who get their surgery from a non-high-volume surgeon tend to not do as well,” Holt said. “If they live outside of a major center, they may get their surgery from somebody who doesn’t operate for thyroid cancer often. If the preop evaluation or surgery are incomplete the patient may have a higher likelihood of recurrence and need for more and riskier surgery down the road.”

The lack of access is not only a geographical issue, according to Pearce.

“There are pretty good data, unfortunately, that Hispanic and Black patients in the U.S. are more likely to see the low-volume surgeons, who do one to nine cases a year, as opposed to the high-volume surgeons, who do more than 100,” Pearce said. “That manifests as worse outcomes for the thyroid cancer, and also in the acute setting, longer hospital stays and higher risk of complications and mortality from the surgery itself.”

Future movement in care should focus on improving access, according to Holt. She said providers need to identify which patients should be referred to a larger center with a high-volume surgeon based on their cancer severity. Additionally, providers should explore ways to assist patients who may struggle to find transportation to a high-volume surgeon a long distance from their home.

References:

• Al-Qurayshi Z, et al. JAMA Otolaryngol Head Neck Surg. 2016;doi:10.1001/jamaoto.2015.2503.
• Haugen BR, et al. Thyroid. 2016;doi:10.1089/thy.2015.0020.
• Maniakas A, et al. JAMA Oncol. 2020;doi:10.1001/jamaoncol.2020.3362.
• Miranda-Filho A, et al. Lancet Diabetes Endocrinol. 2021;doi:10.1016/S2213-8587(21)00027-9.
• Tang J, et al. World J Surg Oncol. 2018;doi:10.1186/s12957-018-1340-7.