Use risk stratification to guide treatment of papillary thyroid microcarcinomas
Key takeaways:
- Multiple predictors were linked to biochemical or structural evidence of disease 1 year after papillary thyroid microcarcinoma diagnosis.
- Risk stratification should be used to guide management of small tumors.
Rather than tumor size alone, the American Thyroid Association’s risk stratification system should be used when assessing papillary thyroid microcarcinomas, according to data published in The Journal of Clinical Endocrinology & Metabolism.
Researchers assessed data from the Italian Thyroid Cancer Observatory of 5,038 patients diagnosed with papillary thyroid carcinoma with at least 1 year of follow-up data available (median age at diagnosis, 49 years; 75% women). Predictors of biochemically or structurally incomplete response for adults with papillary thyroid microcarcinomas included multiple factors such as distant metastases at diagnosis and the use of radioactive iodine therapy during treatment. Additionally, having a high-risk classification according to the ATA risk stratification system raised odds for biochemical and structural evidence of disease at 1 year for patients who underwent a total thyroidectomy plus radioactive iodine therapy.
“While most micro papillary thyroid carcinomas have an indolent course, the identification of predictors like ATA high-risk status can help tailor treatment,” Giorgio Grani, MD, PhD, associate professor of internal medicine at Sapienza University of Rome, told Healio.
Of the study participants, 53.5% had a macro papillary thyroid carcinoma with a tumor of larger than 1 cm, and 46.5% had a papillary thyroid microcarcinoma with a tumor size of 1 cm or less. When tumors were classified according to the ATA risk stratification system, 50.4% were considered low risk, 43.6% were intermediate risk and 6% were deemed high risk. A higher percentage of microcarcinomas were deemed low risk by ATA risk stratification than macro carcinomas (61.8% vs. 40.5%). Macro papillary thyroid carcinomas were more frequently intermediate risk (51.2% vs. 34.8%) or high risk (8.3% vs. 3.4%) than papillary thyroid microcarcinomas (P < .001).
At 1 year, patients with papillary thyroid microcarcinomas were more likely to have excellent or indeterminate response to therapy than those with larger papillary thyroid carcinomas (92.7% vs. 88%).
Patients with microcarcinomas were more likely to have biochemical or structural evidence of disease at 1 year if they had central compartment lymph node metastases (OR = 2.12; 95% CI, 1.18-3.8; P = .01), distant metastases (OR = 3.7; 95% CI, 1.1-12.46; P = .03), were treated with radioactive iodine therapy (OR = 2.04; 95% CI, 1.28-3.26; P < .001) or had a near total thyroidectomy performed (OR = 4.51; 95% CI, 1.76-11.53; P < .001). Distant metastases at diagnosis (OR = 5.13; 95% CI, 1.11-23.73; P = .04) and radioactive iodine therapy (OR = 2.23; 95% CI, 0.99-5.05; P = .05) were associated with higher odds for structural evidence of disease.
In a subgroup of 925 people who had a total thyroidectomy performed and used radioactive iodine, patients were more likely to have biochemical or structural evidence of disease if they were categorized as high risk by ATA risk stratification (OR = 3.67; 95% CI, 1.52-8.84; P < .001), if central neck compartment lymph node metastases was found at initial surgery (OR = 2.69; 95% CI, 1.31-5.53; P = .01) or if a neck lymphadenectomy was not performed (OR = 2.47; 95% CI, 1.21-5.03; P = .01). A classification of high risk was the only predictor associated with higher odds of structural evidence of disease in the subgroup (OR = 5.47; 95% CI, 1.42-21.04; P = .01).
“While small tumor size is a key factor in treatment decisions, our data emphasizes that the ATA risk stratification system should be used and is a reliable predictor of persistence, even in papillary thyroid microcarcinomas,” Grani said. “Therefore, comprehensive risk assessment, rather than relying solely on tumor size, is crucial for guiding management strategies.”
Grani said more research is necessary, including an assessment of risk for recurrence and long-term outcomes with papillary thyroid microcarcinomas.
For more information:
Giorgio Grani, MD, PhD, can be reached at giorgio.grani@uniroma1.it or on X @GiGrani
Perspective
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The incidence of papillary thyroid cancer has increased worldwide, mainly due to the detection of papillary thyroid microcarcinoma, which constitutes up to 50% of cases. Although most papillary thyroid microcarcinomas exhibit indolent growth and a favorable prognosis, some present an increased risk of recurrence and an unfavorable prognosis due to high-risk characteristics.
The early identification of high risk remains elusive. Active surveillance has been proposed as an alternative to surgery for low-risk papillary thyroid microcarcinoma and is defined as regular monitoring for disease progression. This relies on the ability to accurately define low-risk papillary thyroid microcarcinoma and select patients appropriately.
This multicenter prospective study of more than 5,000 patients aimed to identify factors predicting biochemical incomplete response and/or structural incomplete response 1 year after initial treatment. By directly comparing clinical behavior and outcomes between papillary thyroid microcarcinoma and macro papillary thyroid carcinomas, the study looked at risk factors that would portend aggressive behavior, thereby helping tailor treatment. According to ATA risk classification, 50% of patients in the entire cohort were low risk, 43% intermediate risk and 6% high risk.
Papillary thyroid microcarcinoma were more often assigned to the low-risk category. At 1 year, patients with papillary thyroid microcarcinoma were more likely to have excellent or indeterminate response to therapy compared with patients with larger tumors (92% vs. 88%).
Despite their small size and generally favorable biology — evidenced by lower rates of aggressive variants, extrathyroidal extension, distant metastases and higher classification in the ATA low-risk group — these tumors were not universally indolent. Up to 22% exhibited microscopic extrathyroidal extension, and 2% had macroscopic spread, a non-negligible figure that underscores the need for individualized assessment beyond tumor diameter alone.
Presence of central compartment lymph node metastases, distant metastases and use of radioactive iodine therapy were predictors of biochemical incomplete responses and structural incomplete response at 1 year follow-up. In a subgroup of 925 patients who had undergone a total thyroidectomy and received radioactive iodine, predictors of biochemical and structural disease presence included ATA high-risk classification, absence of neck dissection and central neck disease. The sole predictor of structural disease presence was the ATA high-risk status.
Limitations of the study include a short-term follow-up of 1 year, which may not have been sufficient to capture long-term recurrence. The true prognostic value of aggressive histologic subtypes in papillary thyroid microcarcinoma may also be underrecognized.
The study also illuminates key surgical and treatment trends. Total thyroidectomy and radioactive iodine therapy for papillary thyroid microcarcinoma remain prevalent across the world. Data from the U.S. Surveillance, Epidemiology and End Results (SEER) program show a similarly sluggish adoption of conservative surgery, with lobectomy rates plateauing around 25% to 30%. This reflects the fear of undertreatment of potentially aggressive tumors. We need robust risk-stratification of papillary thyroid microcarcinoma to guide appropriate therapy.
These findings reinforce the ATA risk stratification system as a robust tool, even for papillary thyroid microcarcinoma. While the majority merit a conservative approach, a small subset — those with high-risk features — does require closer attention and intensified treatment.
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