Patients With Low-Risk Thyroid Microcarcinoma Benefit More With Active Surveillance

Akira Miyauchi, MD, PhD

Results of a recent study show that patients with low-risk thyroid-related microcarcinoma who choose to undergo immediate surgery are at higher risk for adverse events and unnecessary risk compared with those who decide on active surveillance.

The Japanese study, described this month in an article in Thyroid,¹ found that 974 patients who opted for immediate surgery had significantly higher risks for adverse results than a group of 1179 patients who chose active surveillance. Reported adverse events included vocal cord paralysis, hypothyroidism, need for L-thyroxine, post-surgical hematoma, and surgical scars.

Of those in the active surveillance group, 94 patients had to later undergo surgery for tumor enlargement or lymph node metastasis. No patients had distant metastasis and no fatalities were reported.

However, any treatment or management technique can be associated with unfavorable features. For example, some patients experience anxiety after electing active surveillance.

“Those patients have to come to the tumor hospital once a year; that might be a negative feature,” explained Akira Miyauchi, MD, PhD, visiting professor at Nippon Medical University in Tokyo, and COO of Kuma Hospital in Kobe, Japan, where the study was conducted. Active surveillance, he added, should be considered a standard option for patients with papillary microcarcinoma.

There has been a 2.9-fold increase in the incidence of thyroid cancer in the United States over the past 35 years, though that number is largely due to smaller nodules being detected by increasingly sophisticated imaging modalities.

In 2016, the American Thyroid Association revised their guidelines to revoke the recommendation of fine-needle aspiration for small tumors (<1 cm), even in tumors suspicious for malignancy on ultrasound images, Miyauchi noted.²

In the study, researchers analyzed data from 2153 patients diagnosed at Kuma Hospital with low-risk thyroid papillary microcarcinoma. Low risk was defined as meaning the cancer lacked aggressive features such as nodal or distant metastasis, high-grade appearance on cytology, and worrisome features such as attachment to the trachea or on the course of the recurrent laryngeal nerve.

“If a tumor progresses, those patients could get vocal chord paralysis or hoarseness, or if the trachea is invaded, a larger extent of surgery becomes necessary if we do an operation,” explained Miyauchi.

Of the 2153 patients, 974 chose immediate surgery. All patients were followed for a median of 47 months. Of the 1179 patients who chose active surveillance, 27 (2.3%) later underwent surgery due to tumor enlargement, and 6 additional patients (0.5%) converted to surgery due to the appearance of novel lymph node metastases.

In the group of patients who chose immediate surgery, 4.1% experienced transient vocal cord paralysis, compared with 0.6% of those who elected for active surveillance (P <.0001). Additionally, 2 patients (0.2%) in the immediate surgery group also experienced permanent vocal cord paralysis.

In the immediate surgery group, 16.7% experienced transient hypoparathyroidism, compared with 2.8% of those who elected active surveillance (P <.0001). The rate of permanent hypoparathyroidism was 1.6% among those who elected immediate surgery compared with 0.08% among those who elected active surveillance (P <.0001). The need for L-thyroxine hormone was also greater in those who chose immediate surgery (66.1% vs 20.7%, P <.0001).

While the tumors grew or metastasized to the lymph nodes in some patients who chose active surveillance and later required surgery, there were no unfavorable oncological outcomes.

“If we can identify those patients who will show an increase in tumor size and metastasis at the presentation, we can do immediate surgery only for these high-risk patients,” said Miyauchi. “Age, gender, history, ultrasound features, and cytological features on fine-needle aspiration might be candidates, and also, in the future, some kind of molecular biomarker might be a solution.”

“Patients younger than 40 tend to show growth in tumor size and also the appearance of lymph node metastasis,” he added. “In the classical view of clinical thyroid cancer, older age was associated with poor prognosis, but in these patients with low-risk papillary micro-cancer, it’s the very opposite; in patients older than 60, the instance of lymph node appearance was very low.”

A researcher of Miyauchi’s team is also working on further research measuring the costs of either strategy, which is expected to be submitted within the next 2 months.

“When we consider the cost for one patient over a 10-year period, immediate surgery is 5 times more expensive than active surveillance,” Miyauchi summarized.

Both patients and doctors have grown more willing to opt for active surveillance, Miyauchi said. A previous study found that only 22% of the patients with low-risk disease chose observation,³ while during the present study period, 54.8% of the participants made that choice.

References

1. Oda H, Miyauchi A, Ito Y, et al. Incidences of unfavorable events in the management of low-risk papillary microcarcinoma of the thyroid by active surveillance versus immediate surgery. Thyroid. 2016; 26(1):150-155.
2. Haugen B, Alexander E, Bible K, et al. Guidelines for adult patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2016; 26(1):1-133.
3. Ito Y, Uruno T, Nakano K, et al. An observation trial without surgical treatment in patients with papillary microcarcinoma of the thyroid. Thyroid. 2003;13(4):381—387.