Evaluation of the efficacy of a personalized surgical extent selection algorithm for papillary thyroid microcarcinoma based on immunocytochemical markers of tumor aggressiveness

Abstract

Papillary thyroid microcarcinoma (PTMC) is the most common form of thyroid malignancy and is generally characterized by a favorable clinical course. However, a subset of PTMCs demonstrates aggressive biological behavior, including extrathyroidal extension, regional lymph node metastasis, and an increased risk of recurrence. Current international guidelines, including the 2025 American Thyroid Association (ATA) and National Comprehensive Cancer Network (NCCN) recommendations, advocate a risk-adapted approach with less extensive surgery for patients with low-risk disease. Nevertheless, successful implementation of this strategy requires reliable preoperative tools for assessing tumor aggressiveness. One of the most promising approaches is the integration of immunocytochemical markers into clinical decision-making algorithms using fine-needle aspiration biopsy (FNAB) specimens. Objective. To evaluate the clinical efficacy of a personalized surgical extent selection algorithm for PTMC developed on the basis of preoperative immunocytochemical risk stratification of tumor aggressiveness using CK17, TPO, and S-cells. Materials and Methods. A prospective open-label comparative clinical study was conducted at the Precarpathian Clinical Oncology Center in collaboration with the V.P. Komisarenko Institute of Endocrinology and Metabolism of the National Academy of Medical Sciences of Ukraine between September 2024 and March 2026. A total of 110 patients with cytologically confirmed papillary thyroid microcarcinoma (PTMC) (tumor size ≤10 mm; Bethesda categories V–VI) were enrolled. The control group included 54 patients whose surgical management was determined according to conventional clinical, ultrasonographic, and cytological criteria. The study group comprised 56 patients who additionally underwent preoperative immunocytochemical assessment of fine-needle aspiration biopsy (FNAB) specimens with determination of cytokeratin 17 (CK17), thyroid peroxidase (TPO), and S-cells. The results were incorporated into a personalized risk stratification algorithm for selection of the surgical extent. The primary study endpoints were the proportion of organ-preserving procedures, the rate of regional lymph node metastasis detection, and postoperative complications assessed according to the Clavien–Dindo classification. Secondary endpoints included concordance between preoperative risk prediction and final histopathological findings (Cohen’s κ coefficient) as well as prognostic performance of the algorithm evaluated by receiver operating characteristic (ROC) analysis and the area under the curve (AUC). Statistical analysis was performed using SPSS version 26.0 and MedCalc version 20.0. Odds ratios (ORs) with 95% confidence intervals (CIs), ROC analysis, and Cohen’s κ statistics were applied where appropriate. Differences were considered statistically significant at p < 0.05. Results. The study and control groups were comparable with respect to baseline demographic, clinical, and ultrasonographic characteristics (p > 0.05 for all variables). The proportion of organ-preserving procedures (hemithyroidectomies) was significantly higher in the study group than in the control group (60.7% vs. 33.3%; p = 0.006). The overall postoperative complication rate was significantly lower in the study group (30.4% vs. 50.0%; OR = 0.42; 95% CI: 0.19–0.92; p = 0.037), including major complications (Clavien–Dindo grades III–IV: 1.8% vs. 9.3%; p = 0.045). The frequency of regional lymph node metastasis detection was significantly higher in the study group (53.6% vs. 31.5%; p = 0.019), indicating improved preoperative identification of patients at increased risk of lymphatic tumor spread. The proposed risk stratification algorithm based on the immunocytochemical panel (CK17, TPO, and S-cells) demonstrated excellent prognostic performance, with an AUC of 0.91 (95% CI: 0.84–0.97), an overall accuracy of 85.5%, and substantial agreement between preoperative predictions and final histopathological findings (Cohen’s κ = 0.77; p < 0.001). Conclusions. The proposed five-step preoperative risk stratification algorithm for PTMC aggressiveness, integrating clinical, ultrasonographic, cytological, and immunocytochemical criteria, enables personalized selection of surgical extent and demonstrates high prognostic accuracy (AUC = 0.91; Cohen’s κ = 0.77). Implementation of the algorithm significantly increases the proportion of organ-preserving procedures (60.7% vs. 33.3%; p = 0.006) while reducing the overall rate of postoperative complications (30.4% vs. 50.0%; OR = 0.42; 95% CI: 0.19–0.92; p = 0.037) without compromising oncological safety. The higher rate of regional lymph node metastasis detection in the study group (53.6% vs. 31.5%; p = 0.019) indicates improved preoperative identification of patients at increased risk of lymphatic tumor spread. The risk stratification model based on the combined assessment of CK17, TPO, and S-cells demonstrated excellent discriminatory performance and substantial agreement with final histopathological findings, supporting its potential integration into routine clinical practice. Further multicenter prospective studies are warranted to provide external validation of the proposed algorithm