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Thyroid Cancer Recurrence: Integrating Surgical, Clinical, and Translational Research

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Prof. Dr. Nikola Slijepcevic

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Guest Editor

1. Assoc. Prof., Department of Surgery and Anesthesiology, Medical Faculty, University of Belgrade, Belgrade, Serbia
2. Clinic for Endocrine Surgery, University Clinical Centre of Serbia, Belgrade, Serbia
Interests: thyroid; parathyroid; adrenal; endocrine surgery

Prof. Dr. Ioannis Koutelidakis

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Guest Editor

Second Surgical Department, G. Gennimatas General Hospital of Thessaloniki, Aristotle University of Thessaloniki, Ethnikis Aminis 41, 546 35 Thessaloniki, Greece
Interests: endocrine surgery; endoscopic surgery; surgical education and surgical infections

Special Issue Information

Dear Colleagues,

Thyroid cancer recurrence remains a significant clinical challenge, impacting patient outcomes across all histological subtypes. This Special Issue aims to highlight recent advances in the understanding, detection, and management of recurrent thyroid cancer, with an emphasis on integrating surgical expertise and clinical decision making with current developments in molecular risk stratification, imaging techniques, circulating biomarkers, and response-adapted follow-up strategies. We welcome original research articles, reviews, and case series addressing recurrence risk stratification, surgical innovations, diagnostic imaging, systemic therapies, and the management of rare or aggressive subtypes. By combining translational research with clinical perspectives, this Special Issue provides a platform for advancing comprehensive, evidence-based, and personalized treatment approaches to improve outcomes—particularly for patients with aggressive or radioiodine-refractory thyroid cancer.

Prof. Dr. Nikola Slijepcevic
Prof. Dr. Ioannis Koutelidakis
Guest Editors

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15 pages, 1024 KB

Open AccessArticle

Unmeasurable Stimulated Thyroglobulin Before Radioactive Iodine Ablation Predicts Excellent Long-Term Outcomes in Patients with Differentiated Thyroid Cancer

by Yi Sia and Radu Mihai

Cancers 2026, 18(7), 1058; https://doi.org/10.3390/cancers18071058 - 25 Mar 2026

Viewed by 432

Abstract

Background: There is ongoing interest in limiting the extent of treatment for patients with low-risk differentiated thyroid cancer (DTC) and in redesigning individualised follow-up strategies. This study assessed long-term outcomes in patients with excellent response to surgical treatment demonstrated by reaching unmeasurable stimulated thyroglobulin (sTG) levels before proceeding with radioactive iodine ablation. Methods: This is a retrospective cohort study of consecutive patients treated for DTC in a tertiary referral centre. Radioactive iodine ablation (RIA) was done after hormone withdrawal (before 2015) or after Thyrogen stimulation (in recent years). The biochemical assay for TG changed from a lower limit of detectability of 5 ng/mL to 0.2 ng/mL in 2012. Results: Of 331 patients operated on between 2001 and 2019, unmeasurable sTG was measured in 70 of 138 patients (51%) when using an assay with threshold of 5 ng/mL and in 38 of 193 patients (20%) based on the threshold of 0.2 ng/mL. Compared with patients whose sTG was >5 ng/mL, those with sTG <5 ng/mL (187 of 331 patients) were less likely to have T3–T4 tumours or positive lymph node disease (N1a–N1b) and had a lower MACIS score (5.73 ± 1.26 vs. 6.45 ± 1.69, p < 0.001) and much lower mortality with metastatic disease during follow-up for 100 ± 48 months (3/187 vs. 23/144 patients, p = 0.001). Conclusions: Patients with unmeasurable sTG have excellent prognosis, with very low incidence of adverse events. With the wide use of TG assay with a threshold of 0.2 ng/mL (or lower), this subgroup could have patient-initiated follow-up rather than embark on regular assessments. Full article

(This article belongs to the Special Issue Thyroid Cancer Recurrence: Integrating Surgical, Clinical, and Translational Research)

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20 pages, 5169 KB

Open AccessArticle

Clinical Behavior of Aggressive Variants of Papillary Thyroid Carcinoma: A Retrospective Case–Control Study

by Jovan Ilic, Nikola Slijepcevic, Katarina Tausanovic, Bozidar Odalovic, Goran Zoric, Marija Milinkovic, Branislav Rovcanin, Milan Jovanovic, Matija Buzejic, Duska Vucen, Boban Stepanovic, Sara Ivanis, Milan Parezanovic, Milan Marinkovic and Vladan Zivaljevic

Cancers 2026, 18(2), 345; https://doi.org/10.3390/cancers18020345 - 22 Jan 2026

Cited by 1 | Viewed by 610

Abstract

Background/Objectives: Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. The classic variant (cPTC) is characterized by indolent behavior and excellent prognosis. However, rare subtypes of PTC most often exhibit adverse clinical behavior. The aim of the study was to assess the aggressiveness of rare variants of PTC by analyzing clinicopathological characteristics (CPCs) and survival outcomes. Methods: We analyzed 80 patients with rare PTC variants treated between 2009 and 2019 who were compared with cPTC and matched with a control group for age and tumor size. The variants were categorized into high-risk (HRV: tall cell, diffuse sclerosing, columnar cell, and hobnail variants), intermediate-risk (IRV: solid variant (SV)), and low-risk (LRV: oncocytic (OV) and Warthin-like (WLV)) variants. Different CPCs (capsule and blood vessel invasion, lymphonodal metastases, microscopic and macroscopic extrathyroid extension, multifocal and bilateral presentation) and survival outcomes—overall (OS), disease-specific (DSS), and disease-free survival (DFS) were compared. Results: HRVs exhibited significantly more aggressive CPCs and worse OS, DSS, and DFS compared to cPTC (p < 0.001). IRVs showed no significant difference in CPCs or survival outcomes compared to cPTC. LRVs showed excellent survival but were associated with several unfavorable CPCs. Multivariate analysis identified classification in HRVs as the only independent predictor of recurrence (p = 0.014). Conclusions: Tumors in the HRV group should retain their status as aggressive PTC variants due to unfavorable behavior and poorer prognosis. SVs, despite earlier assumptions, do not exhibit aggressive characteristics. Although the OV and WLV have similar survival to cPTC, their potential for adverse CPCs requires caution. Full article

(This article belongs to the Special Issue Thyroid Cancer Recurrence: Integrating Surgical, Clinical, and Translational Research)

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