Personalization of the extent of surgical treatment for papillary thyroid carcinoma based on preoperative immunocytochemical risk stratification

Abstract

Papillary thyroid microcarcinoma (PTMC) is the most commonly diagnosed form of thyroid cancer and generally has a favorable prognosis. However, a subset of PTMCs exhibits an aggressive biological course characterized by extrathyroidal extension, regional lymph node metastasis, and recurrence. Current recommendations of the American Thyroid Association (ATA) and the National Comprehensive Cancer Network (NCCN) (2024) support less extensive surgical treatment, when indicated, in patients at low risk; however, implementation of this approach requires reliable methods for preoperative stratification of tumor aggressiveness. Immunocytochemical markers may provide a promising approach for predicting the biological behavior of PTMC at the preoperative stage. Objective — to evaluate the effectiveness of a combined preoperative panel of immunocytochemical markers (cytokeratin 17, thyroid peroxidase, and S-cells) for risk stratification of aggressive papillary thyroid microcarcinoma and personalization of the extent of surgical treatment. Materials and methods. A prospective comparative study was conducted in 110 patients with cytologically verified PTMC (Ј 10 mm) who were treated at the Precarpathian Clinical Oncology Center in 2024 — 2026. The control group included 54 patients whose extent of surgery was determined according to standard clinical, ultrasonographic, and cytological criteria. The study group comprised 56 patients who additionally underwent preoperative immunocytochemical assessment of cytokeratin 17 (CK17), thyroid peroxidase (TPO), and S-cells, followed by risk stratification. The extent of surgical intervention, frequency of regional metastasis, postoperative complications, predictive performance of the model [ROC analysis and area under the ROC curve (AUC)], and concordance between the preoperative prediction and histopathological findings (Cohen’s k) were assessed. Results. In the study group, the proportion of organ-sparing procedures was significantly higher than in the control group (60.7% vs. 33.3%, p=0.004), while the overall rate of postoperative complications was lower (30.4% vs. 50.0%; odds ratio, 0.44; 95% confidence interval, 0.20 — 0.95; p=0.036). The detection rate of regional metastases was higher in the study group (53.6% vs. 31.5%, p=0.019), which was associated with more targeted selection of patients for extended surgical staging. The combined model (CK17, TPO, and S-cells) demonstrated high predictive performance, with an area under the ROC curve of 0.91 (95% confidence interval, 0.84 — 0.97), an overall accuracy of 85.5%, and substantial agreement with histopathological findings (k=0.77; p<0.001). Conclusions. Preoperative stratification of PTMC aggressiveness using a combined panel of CK17, TPO, and S-cells may enable personalization of the extent of surgical treatment. In the study group, the proportion of justified organ-sparing procedures was higher, while the overall rate of postoperative complications was lower than in the control group. Regional metastases were detected more frequently in the study group; this finding may have been influenced by the extent of lymph node dissection. The combined model demonstrated high predictive performance (AUC=0.91) and may be considered a promising tool for preoperative risk stratification in patients with PTMC.