Study Reaffirms Favorable Outcomes for Small Papillary Thyroid Cancers

Thyroid gland: © Anatomy Insider - stock.adobe.com

An Italian study (NCT04031339) has found that patients with papillary thyroid carcinoma (PTC) smaller than 1 cm (microPTC) typically experience more favorable outcomes compared with patients whose tumors are larger (macroPTC), particularly 1 year after surgery. The study also confirmed the reliability of the American Thyroid Association (ATA) risk classification system in predicting persistent or recurrent disease. ¹

Researchers led by De Leo and colleagues analyzed data from 5038 PTC patients in the Italian Thyroid Cancer Observatory, a web-based database, to assess clinical and pathological predictors of biochemical incomplete response (BIR) and structural incomplete response (SIR) 1-year post-treatment.

Patient cases were selected if they contained a histological diagnosis of PTC, if results at 1-year follow-up were available, and if the patients were treated at high-frequency clinical centers. The study evaluated multiple factors to determine biochemical or structural incomplete response such as having distant metastases at diagnosis and the use of radioactive iodine therapy during treatment. Notably, 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.

The investigators determined that 2345 patients (46.5%) had microPTC and 2693 (53.5%) had macroPTC. According to ATA risk classification, 2539 (50.4%) tumors of the entire cohort were categorized as low-risk, 2197 (43.6%) as intermediate-risk, and 302 (6%) as high-risk. MicroPTC were more likely classified as low-risk class; in particular, microPTC and macroPTC were, respectively, low-risk tumors in 61.8% and 40.5%, intermediate-risk tumors in 34.8% and 51.2%, and high-risk tumors in 3.4% vs 8.3% of cases (P < .001).

At the 1-year follow-up, patients with microPTC were more frequently characterized by an excellent or indeterminate response (92.7%) compared with patients with macroPTC (88.0%).

The investigators reported that the presence of distant metastases at diagnosis were the best predictor of SIR in microPTCs (OR, 5.13; 95% CI, 1.11-23.73; P =.04). While prior studies linked older age, extrathyroidal extension, and lymph node metastases to distant metastases in microPTC, these factors did not predict SIR in this analysis.²

The investigators also examined a subgroup of 925 patients who underwent total thyroidectomy and radioactive iodine treatment. This cohort excluded patients with distant metastases due to the low frequency of the event. Within this subgroup, the ATA high-risk classification was the sole predictor of SIR. In this cohort, the best predictor of SIR was the ATA high risk (OR, 5.47; 95% CI,1.42-21.04; P =.01). Notably, the risk of SIR was not increased in the presence of central compartment lymph node metastases, which influenced only BIR at the 1-year evaluation following initial treatment.

According to investigators, the main limitation of the study is the lack of follow-up after 1 year from the initial treatment. However, because of the good response to treatment of these tumors, the results of this study are reassuring about the outcome of the majority of these cancers, which are effectively in remission after 1 year.

The investigators concluded that “these findings underscore the importance of tailored management strategies based on comprehensive risk stratification, rather than solely on tumor size.”

REFERENCES:

1. De Leo S, Brigante G, D'Elia S, et al. Prospective validation of ATA risk score for papillary thyroid microcarcinoma: an ITCO real-world study. J Clin Endocrinol Metab. 2025. doi:10.1210/clinem/dgaf190

2. Huang H, Xu S, Wang X, Liu S, Liu J. Patient age is significantly related to distant metastasis of papillary thyroid microcarcinoma. Front Endocrinol (Lausanne). 2021;12:748238. doi:10.3389/fendo.2021.748238