The Initial Risk Stratification System for Differentiated Thyroid Cancer: Key Updates in the 2024 Korean Thyroid Association Guideline

Shinje Moon; Young Shin Song; Kyong Yeun Jung; Eun Kyung Lee; Jeongmin Lee; Dong-Jun Lim; Chan Kwon Jung; Young Joo Park

doi:10.3803/EnM.2025.2465

Articles

Page Path: HOME > Endocrinol Metab > Volume 40(3); 2025 > Article

Review Article Thyroid The Initial Risk Stratification System for Differentiated Thyroid Cancer: Key Updates in the 2024 Korean Thyroid Association Guideline Keypoint -In 2024, the Korean Thyroid Association (KTA) introduced a revised Risk Stratification System for differentiated thyroid cancer. -The histological classification follows the 2022 World Health Organization classification. It consolidates encapsulated follicular-patterned thyroid carcinomas, including invasive encapsulated follicular variant papillary thyroid carcinoma, follicular thyroid carcinoma, and oncocytic carcinoma of the thyroid gland, and stratifies them by the extent of capsular and vascular invasion. High-grade thyroid carcinoma is newly included. -Updated criteria for tumor size and extrathyroidal extension represent another significant change. -BRAFV600E-mutated papillary thyroid carcinomas measuring 1 to 2 cm are now considered lower risk. -Encapsulated follicular-pattern tumors larger than 4 cm are considered higher risk. -Both minimal ETE and gross ETE confined to the strap muscles have been downgraded to low and intermediate risk, respectively.: Shinje Moon^1*, Young Shin Song^2*, Kyong Yeun Jung³, Eun Kyung Lee⁴, Jeongmin Lee⁵, Dong-Jun Lim⁶, Chan Kwon Jung⁷, Young Joo Park^8,9, on Behalf of the Korean Thyroid Association Clinical Guideline Committee; Endocrinology and Metabolism 2025;40(3):357-384.
DOI: https://doi.org/10.3803/EnM.2025.2465
Published online: June 24, 2025

¹Department of Internal Medicine, Hanyang University Seoul Hospital, Seoul, Korea

²Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea

³Department of Internal Medicine, Nowon Eulji Medical Center, Eulji University, Seoul, Korea

⁴Department of Internal Medicine, National Cancer Center, Goyang, Korea

⁵Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea

⁶Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea

⁷Department of Hospital Pathology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea

⁸Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea

⁹Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea

Corresponding authors: Eun Kyung Lee. Department of Internal Medicine, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 10408, Korea Tel: +82-31-920-1743, Fax: +82-31-920-1789, E-mail: eklee@ncc.re.kr

Young Joo Park. Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea Tel: +82-2-2072-4183, Fax: +82-2-762-2292, E-mail: yjparkmd@snu.ac.kr

*These authors contributed equally to this work.

• Received: May 21, 2025 • Revised: May 23, 2025 • Accepted: May 26, 2025

This guideline has been originally written in Korean and published in the International Journal of Thyroidology 2024;17(1):68-96.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

625 Views
55 Download

prev next

Full Article

Download PDF

ABSTRACT
INTRODUCTION
KEY DIFFERENCES OF K-RSS (2024 KTA) FROM THE M-RSS (2015 ATA)
EVIDENCE SUMMARY OF THE KTA INITIAL RISK STRATIFICATION SYSTEM (K-RSS)
CONCLUSIONS
Supplementary Material
Article information
References

ABSTRACT

In 2024, the Korean Thyroid Association (KTA) introduced a revised Risk Stratification System (K-RSS) for differentiated thyroid cancer, building upon the modified RSS (M-RSS) proposed by the American Thyroid Association in 2015. The K-RSS emphasizes the cumulative impact of coexisting clinical and pathological features, acknowledging that multiple intermediate-risk factors collectively indicate a higher recurrence risk. Histologic classification follows the 2022 World Health Organization classification, consolidating encapsulated follicular-patterned thyroid carcinomas, including invasive encapsulated follicular variant papillary thyroid carcinoma, follicular thyroid carcinoma, and oncocytic carcinoma of the thyroid gland, and stratifying them by the extent of capsular and vascular invasion. High-grade thyroid carcinoma is newly included. Updated criteria for tumor size and extrathyroidal extension (ETE) represent another significant change. BRAF^V600E-mutated papillary thyroid carcinomas measuring 1 to 2 cm are now considered lower risk than previously classified in the M-RSS, while encapsulated follicular-patterned tumors larger than 4 cm are considered higher risk. Both minimal ETE and gross ETE confined to the strap muscles have been downgraded to low and intermediate risk, respectively. These changes are accompanied by updates regarding molecular profiling and surgical margin status. Collectively, these updates aim to minimize overtreatment in low-risk patients, while ensuring intensified management for those at higher risk.
Keywords: Differentiated thyroid cancer; Risk assessment; Prognosis; Recurrence; Guideline; Korean

INTRODUCTION

The primary goal of initial treatment for differentiated thyroid cancer (DTC) is to improve overall and disease-specific survival, while minimizing treatment-related morbidity and avoiding unnecessary interventions [1,2]. Accurate staging and risk stratification not only predict recurrence but also guide decisions on the extent of surgery, radioactive iodine (RAI) therapy, and thyroid-stimulating hormone (TSH) suppression [2,3]. Although the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging system reliably estimates disease-specific mortality, it does not address recurrence risk [4]. To fill this gap, the American Thyroid Association (ATA) introduced a Risk Stratification System (RSS) in 2009, incorporating lymph node (LN) metastases, genetic mutations, and vascular invasion in follicular thyroid carcinoma (FTC) [5]. In 2015, the ATA revised it into a modified RSS (M-RSS), estimating recurrence risk on a continuous scale (1% to >50%) and categorizing patients as low (<5%), intermediate (5%–20%), or high (≥20%) risk [2].

Clinical practice in Korea, however, has underscored the need to update the 2015 M-RSS. Factors such as a high prevalence of BRAF^V600E mutations, broader adoption of lobectomy, and extensive experience in high-volume centers can influence risk estimates. Moreover, the 2022 World Health Organization (WHO) classification of endocrine and neuroendocrine tumors introduced detailed pathological features that have emerged as novel prognostic indicators; these are not incorporated into the current M-RSS [6,7]. Therefore, patients subclassified according to the WHO classification cannot be adequately accommodated within the existing RSS framework, raising concerns about potential misclassification. Specifically, the prognostic impact of each pathological feature may depend on concurrent features—an interaction that the current M-RSS does not fully address.

To address these issues, the 2024 Korean Thyroid Association (KTA) developed a newly revised RSS (K-RSS) based on the M-RSS, through a comprehensive literature review aimed at quantifying recurrence rates for individual risk factors while minimizing confounding influences. This review summarizes the updated KTA recommendations for ‘Initial assessment and recurrence risk stratification after surgery for DTC,’ highlights key differences between K-RSS (2024 KTA) and M-RSS (2015 ATA), and presents the evidence supporting these revisions [8].

KEY DIFFERENCES OF K-RSS (2024 KTA) FROM THE M-RSS (2015 ATA)

In the 2024 KTA guideline, the importance of postoperative pathological diagnosis and specimen evaluation according to the 2022 WHO classification was emphasized, as summarized in Table 1 and Supplemental Table S1 (Recommendations I.4.1.A–I.4.3.C in 2024 KTA Guidelines) [3]. These clinicopathological factors have been comprehensively incorporated into the updated K-RSS to facilitate the categorization of patients into low-, intermediate-, or high-risk groups. The detailed framework of the K-RSS is presented in Table 2, and key differences between K-RSS and M-RSS are summarized in Tables 3, 4.

The K-RSS applies consistent numeric thresholds, using ‘≤’ to designate the lower cutoff and ‘>’ for upper cutoff levels, to enhance clarity and consistency, ensuring patients whose estimated risk falls exactly at a cutoff point are neither upstaged nor overtreated. Recurrence risks in the K-RSS are defined based on 10-year recurrence probabilities, whenever possible, derived from published clinical studies, particularly those involving Korean cohorts. Risks are stratified as low risk (≤5%, with slight overruns considered low), intermediate risk (>5% to ≤30%), and high risk (>30%).

Instead of assessing each risk factor individually, the K-RSS emphasizes a comprehensive evaluation of all clinical and pathological risk factors, considering their combined effects. It recognizes that co-occurrence of multiple intermediate-risk factors may elevate a patient’s overall recurrence risk into the high-risk category, even without a single high-risk feature (Table 1).

The K-RSS also updates histologic classification in accordance with the 2022 WHO classification by grouping invasive encapsulated follicular variant papillary thyroid carcinoma (I-EFVPTC), FTC, and oncocytic carcinoma of the thyroid (OCA) gland into a unified category of encapsulated or circumscribed follicular-patterned thyroid carcinoma. These tumors are stratified as follows: minimally invasive tumors are classified as low risk; encapsulated angioinvasive tumors with up to three foci of vascular invasion are intermediate risk; and tumors with four or more vascular foci or widely invasive tumors are considered high risk. The same vascular invasion criteria are applied to papillary thyroid carcinoma (PTC), despite limited direct supporting evidence (Table 4). Additionally, high-grade thyroid carcinomas, including high-grade differentiated thyroid carcinoma (HGDTC) and poorly differentiated thyroid carcinoma (PDTC), are newly included in the high-risk group.

Additional updates include classifying tumors harboring concurrent high risk mutations such as telomerase reverse transcriptase (TERT) promoter mutations alongside BRAF^V600E or RAS as high-risk, reflecting recurrence rates up to 40% observed in clinical studies. Consequently, the KTA recommends considering postoperative testing for these three mutations in pathological specimens to aid risk assessment (Table 4). In contrast, when present without other risk features, BRAF^V600E-only PTCs measuring 1 to 2 cm are downgraded to low risk, while FTC/OCA/I-EFVPTC larger than 4 cm are upgraded to intermediate risk based on available FTC-related data (Table 4). Additional refinements include downgrading tumor multifocality and microscopic extrathyroidal extension (ETE) to low risk when isolated, and upgrading R1 resection margin (microscopic residual disease) to intermediate risk. The risks associated with extranodal extension (ENE) and metastatic LN ratio are not incorporated into the current K-RSS, pending further evidence of their independent prognostic value. Although specific thresholds for inappropriate serum thyroglobulin (Tg) levels are not defined, the KTA recommends measuring serum Tg (both TSH-stimulated and non-stimulated) postoperatively to assess residual disease and predict potential recurrence (Table 1).

Low-risk group: The low-risk group is defined as cases with a reported recurrence risk of 5% or less. Cases with recurrence risks slightly exceeding 5% (by approximately 1% to 2%) are also included in this category. In most instances, lobectomy is sufficient treatment, and when total thyroidectomy is performed, additional RAI ablation is generally not recommended.; The M-RSS categorized intrathyroidal PTCs measuring ≤4 cm with wild-type BRAF and those ≤1 cm with the BRAF^V600E mutation as low-risk [2,9]. However, in iodine-sufficient regions such as Korea or Italy, where the BRAF^V600E mutation is highly prevalent, tumor size must be considered when interpreting the prognostic significance of the BRAF^V600E mutation in risk stratification. Specifically, BRAF^V600E-mutated PTCs ≤1 cm (papillary thyroid microcarcinomas [PTMCs]) exhibit a 5-year recurrence rate of 2.4% to 2.6%, whereas tumors measuring 2 to 4 cm have recurrence rates around 16.5% [10,11]. Based on a comprehensive committee review, the K-RSS reclassifies BRAF^V600E-mutated PTCs measuring 1 to 2 cm as low-risk, reflecting their relatively indolent outcomes in iodine-sufficient settings (Table 5) [10,12-18]. BRAF^V600E-mutated PTMCs remain classified as low-risk in the K-RSS.; In contrast, although data specific to PTC are limited, intrathyroidal tumors larger than 4 cm—even without other high-risk pathological features—demonstrate recurrence rates of around 8.3% [12]. Consequently, BRAF^V600E -mutated PTCs >2 cm remain classified as intermediate-risk, while BRAF wild-type PTCs measuring 2 to 4 cm continue to be classified as low-risk (Table 5).; Key factors associated with recurrence risk in FTC include tumor size, capsular invasion, and vascular invasion. These factors often co-occur. A systematic review of five studies found that tumor size was not significantly associated with recurrence risk in three studies (Table 5) [19-22]; however, one study observed an increase in recurrence risk with increasing tumor size [23], and another reported an increased risk only in minimally invasive FTC ≥4 cm, but not in widely invasive FTC [24]. Although a cohort study from the USA found that encapsulated or circumscribed follicular-patterned thyroid carcinomas >4 cm, without vascular invasion and confined to the thyroid, showed no recurrence over 10 years—suggesting favorable prognosis [25]—a recent meta-analysis focusing on minimally invasive FTC indicated variable recurrence rates: 1.1%–9.8% for tumors ≤4 cm, and 5.9%–16.7% for tumors >4 cm [24,26-28]. Given this uncertainty, the current guideline exclude minimally invasive FTCs >4 cm from the low-risk category (Table 3). Nonetheless, the prognosis of FTC appears influenced more by accompanying pathological features than tumor size alone; thus, recurrence risk in FTC should be assessed primarily based on the presence and extent of capsular and vascular invasion rather than on tumor size alone.; The 2022 WHO classification was the first to propose stratifying encapsulated or circumscribed follicular-patterned thyroid carcinomas, including FTC, OCA, and I-EFVPTC, into three subtypes: minimally invasive, encapsulated angioinvasive, and widely invasive (Table 4) [6]. For encapsulated or circumscribed follicular-patterned thyroid carcinomas other than FTC, detailed pathological features independently predicting recurrence have not yet been established. Nevertheless, the current guideline recommend applying the same classification criteria used for FTC to these tumors, prioritizing their molecular and pathological similarities despite possible differences in clinical behavior. Further research is needed to provide definitive evidence to refine this approach.; Many international guidelines classify FTC recurrence risk based on capsular and vascular invasion status [2,4,9]. Consistent with this, the KTA guideline adopts a similar approach, emphasizing that the presence and degree of vascular invasion is associated with higher risk than described in previous RSSs, based on emerging clinical evidence (Table 6):; - Minimally invasive FTC (tumor capsular invasion only): Recurrence rate of 0%–5% → Low-risk group [29-31]; - Encapsulated angioinvasive FTC with 1–3 foci of vascular invasion: Recurrence rate of 1.9%–15.2% → Intermediate-risk group [32-37]; - Encapsulated angioinvasive FTC with ≥4 foci of vascular invasion: Recurrence rates of 17.9%–44.4% → High-risk group [32-37]; - Widely invasive FTC: Recurrence rates of 12.7%–54% → High-risk group [24,30,31,35,36,38-42]; For PTC, although recurrence rates according to the exact number of vascular invasion foci have not been clearly established, several studies have demonstrated an association between vascular invasion and increased recurrence risk, reporting recurrence rates ranging from 10.7% to 28.0% [43-47]. Additionally, reported incidences of distant metastasis range from 12.8% to 31.3% in the presence of vascular invasion, suggesting that vascular invasion is also linked to a higher risk of distant metastasis (Table 7) [43-47]. Therefore, among PTCs, only cases without vascular invasion are classified as low-risk. Due to insufficient clinical evidence regarding specific risk stratification based on the number of vascular invasions in PTC, the K-RSS applies FTC criteria to PTC until further evidence is available.; ETE refers to the invasion of thyroid cancer beyond thyroid parenchyma into surrounding tissues. ETE is categorized as minimal (microscopic) or gross (macroscopic), depending on invasion extent. In cases with minimal ETE extending into perithyroidal soft tissues, recurrence rates vary widely (1.5% to 26%) depending on concurrent LN or distant metastasis (Table 8) [15,48-69]. However, when minimal ETE is present alone, without LN or distant metastasis, a meta-analysis of seven studies reported recurrence rates ≤3.5% [53]. Similar low recurrence rates were also observed in patients with uncertain LN status (Nx) [51,57,64]. Therefore, the current guideline does not consider minimal ETE alone an independent risk factor for recurrence.; The recurrence rate of multifocal PTMC (≤1 cm) has been reported to range between 4% and 6%, compared to 1%–2% in unifocal PTMCs [2,70-73]. When multifocality is accompanied by ETE and BRAF^V600E mutation, recurrence rates reportedly increase up to 20%. Accordingly, the M-RSS and European Society of Medical Oncology (ESMO) guidelines classify such cases as intermediate risk [2,9].; Our committee comprehensively reviewed previous studies (Table 9) [15,72,74-85], finding recurrence rates for multifocal PTMC with unknown BRAF status ranging from 0.8% to 11.8% [72,76,85]. When gross ETE or LN metastasis (pN1a or pN1b) is present, the recurrence rate may increase to 23% [85]. For multifocal PTC larger than 1 cm, recurrence rates ranged from 4% to 23%; however, cases without LN metastasis showed significantly lower recurrence rates (0.6% to 2.2%) [86].; One Korean study reported a 5-year recurrence rate of 6.6% for multifocal PTC patients, approximately half of whom had concurrent LN metastasis [72]. This rate was higher than the 2.4% observed in multifocal PTMC cases within the same study, exceeding the 5% threshold for 10-year recurrence. Although data summarized in Table 9 suggest multifocal PTCs, especially those larger than 1 cm, often exhibit recurrence rates exceeding 5% at 10 years, these findings largely reflect patient cohorts with additional high-risk features, such as LN or distant metastases and gross ETE. Therefore, the isolated prognostic impact of multifocality remains uncertain in the absence of additional risk factors.; Based on these considerations and acknowledging the relatively high prevalence of multifocality, the K-RSS does not classify multifocality alone as an independent risk factor. Nonetheless, even in multifocal PTMC, recurrence risk should be comprehensively evaluated in the context of coexisting clinicopathological features.; Further evidence is needed to clarify the independent prognostic significance of multifocality, including whether bilateral multifocal tumors carry recurrence risks similar to those confined to a single lobe.; Both the size and number of metastatic LNs significantly influence recurrence risk (Tables 10, 11). Several studies have reported approximately 5% recurrence rates in cases with LN micrometastases (≤2 mm) [87]. When LN metastases are present but measure less than 3 cm, recurrence rates vary between 1.8% and 12%, depending on the number of involved LNs and presence of ENE [88].; Regarding the number of involved LNs, recurrence rates range from 3% to 8% (median 4%) when there are five or fewer metastatic LNs, and increase to 7%–21% (median 19%) when the number exceeds five [2]. Similar trends have been observed in Korean populations. A multicenter Korean study of 3,282 patients with PTC <2 cm reported a 10-year recurrence risk of 4% with fewer than two metastatic LNs, rising to 16.8% with two or more metastatic LNs [89]. Another Korean study of 2,384 PTC patients reported 10-year recurrence rates of 1.2% without LN metastasis, 3% with 1–5 positive LNs, 12.9% with 6–10 positive LNs, and 27.7% with more than 10 metastatic LNs [90].; Based on these findings, and in alignment with the M-RSS, the current guideline defines LN micrometastases as metastatic LNs ≤2 mm in size, classifying patients with five or fewer micrometastases as low-risk in the K-RSS.
Intermediate-risk group: This guideline defines the intermediate-risk group as patients not meeting criteria for either low- or high-risk categories. For each patient, clinicians should assess clinicopathologic risk factors listed in Tables 5-12 and comprehensively evaluate recurrence risk to determine the treatment strategy [8]. Within this group, treatment recommendations are based on estimating recurrence rates through an integrated assessment of multiple clinicopathological factors rather than evaluating each factor independently. The combined effects of coexisting features must be considered, as multiple intermediate-risk features may justify reclassification into the high-risk group. Relevant factors include ETE, resection margin status, vascular invasion, tumor size, multifocality, characteristics of metastatic LNs (e.g., size, number, ratio, and ENE), and findings from initial post-radioiodine therapy scans. This group is generally considered eligible for completion thyroidectomy and adjuvant RAI therapy. However, recurrence risk in this category spans a broad range (5% to 30%), necessitating individualized treatment decisions. For patients at the lower end of the intermediate-risk spectrum, such as those with an estimated recurrence risk of 5%–10% or approximately 15%, decisions regarding additional therapy should be guided by shared decision-making. This process involves detailed discussions about estimated recurrence risks, potential benefits and risks of further treatment, and patient preferences.; Gross ETE involving only the strap muscles has been reported with recurrence rates ranging from 5.9% to 29.4%, and cancer-specific mortality rates between 1.1% and 3.6%. These outcomes are lower compared to cases with gross ETE extending to other critical structures, such as the recurrent laryngeal nerve or trachea (Table 8) [48-50,52,54,55,57,58,60,62,63,66,68,91,92].; In Korean studies, recurrence rates for isolated gross ETE confined to strap muscles have been reported between 5.9% and 10.8% (Table 8) [60,66]. Additionally, some studies indicate that small subcapsular thyroid cancers do not exhibit increased recurrence risks even with gross ETE [93,94]. Based on this evidence, gross ETE limited to strap muscles (pT3b) has been reclassified as intermediate-risk in the K-RSS.; The completeness of surgical resection for thyroid cancer is generally classified into three categories: R0, defined as no gross residual disease with negative resection margins on histopathological examination; R1, indicating no gross residual disease but positive margins on histopathology (i.e., microscopic residual disease); and R2, indicating the presence of gross residual disease [95,96].; Although long-term survival outcomes typically are similar between R0 and R1 resection, several studies have shown that R1 resection margins are associated with increased recurrence risk, with reported rates ranging from 3.85% to 10.9% [97-99]. One study found lower recurrence-free survival among patients with positive margins (71%) than among those with negative margins (90%) [98]. Another study reported a local recurrence rate of 4.7% (6/127) and demonstrated that using shaving techniques to achieve an R0 resection significantly reduced the local recurrence rate from 25.0% to 0.9% [94,100]. Based on these findings, the K-RSS classifies R0 resection as low-risk and R1 resection as intermediate-risk.; As outlined above, current evidence remains insufficient to definitively determine the prognostic impact of the number of vascular invasions specifically in PTC (Table 7). Therefore, this guideline applies the same classification criteria used for FTC to PTC: the presence of 1–3 foci of vascular invasion is categorized as intermediate risk, whereas involvement of 4 or more foci is classified as high risk. Further research is necessary to validate the appropriateness of this classification specifically for PTC.; The tall cell, columnar cell, and hobnail subtypes are classified as aggressive histologic subtypes in the 2022 WHO classification. These subtypes typically occur in older patients and are often associated with vascular invasion, advanced pathological stage, and high recurrence rates: 22%–37% for the tall cell subtype [101-108], 42% for the columnar cell subtype [109-111], and 23%–35.5% for the hobnail subtype [109,112,113]. However, recurrence risk tends to be lower in smaller tumors and when other pathological risk factors are absent (Table 12). Thus, the K-RSS classifies these subtypes as intermediate-risk. Nevertheless, given that recurrence rates exceed the 30% threshold in some studies, close clinical attention is warranted, particularly regarding the presence of ETE, nodal metastasis, or vascular invasion.; The diffuse sclerosing and solid/trabecular subtypes were not specified as aggressive subtypes in the 2022 WHO classification or the M-RSS. However, in this guideline, both subtypes are classified as intermediate-risk. For the diffuse sclerosing subtype, data from the Surveillance, Epidemiology, and End Results (SEER) database indicated a 5-year cancer-specific survival rate of 96.1%, comparable to classic PTC (97.4%) [103,114,115]. Nevertheless, an extensive literature review (Table 12) showed significant risks of distant and LN metastasis, with recurrence rates ranging from 11.6% to 27%. Similarly, the solid/trabecular subtype demonstrated recurrence rates between 9.5% and 26%, supporting its classification as intermediate-risk [110,116-119].
High-risk group: The high-risk group includes patients with a known recurrence risk exceeding 30%, those with persistent disease, or those at high risk for distant metastasis. If a lobectomy was performed, completion thyroidectomy should be considered, and depending on disease status, additional treatments including RAI therapy and TSH suppression should be pursued.; In the 2022 WHO classification, tumors derived from thyroid follicular cells exhibiting high-grade histologic features, such as increased mitotic activity and tumor necrosis, were redefined as high-grade thyroid carcinomas (high-grade follicular cell-derived non-anaplastic thyroid carcinomas) [6]. Depending on whether the tumor retains typical differentiated nuclear features or architectural patterns, these tumors are further classified as HGDTC or PDTC. PDTC frequently presents with distant metastasis in 19%–39% of cases at diagnosis and carries a 5-year cancer-specific survival rate of only 66% to 70%, supporting its classification as a high-risk tumor [120-124]. Although data for HGDTC remain limited, this subtype is also classified as high-risk alongside PDTC in this guideline.; In the M-RSS, gross ETE involving only strap muscles (T3b) was classified as high-risk. However, based on recurrence rates reported (5.9% to 29.4%) (Table 8), this has been reclassified as intermediate-risk in the K-RSS, as described earlier. In contrast, gross ETE extending beyond the strap muscles (pT4), with recurrence rates ranging from 19.7% to 57.5% (Table 8), and gross residual disease post-surgery (R2) remain classified as high-risk.; Encapsulated angioinvasive FTC with four or more foci of vascular invasion and widely invasive FTC are classified as high-risk, based on their reported recurrence rates of 17.9%–44.4% and 12.7%–54%, respectively (Table 6) [32-36,39-42]. For other encapsulated follicular-patterned thyroid carcinomas (OCA and I-EFVPTC) and PTC, evidence regarding how the degree of vascular invasion specifically correlates with prognosis is currently insufficient. However, based on established associations observed in FTC between the extent of vascular invasion and outcomes such as distant metastasis and overall prognosis, this guideline adopts the same classification across all encapsulated follicular-patterned thyroid carcinomas and PTCs: tumors with four or more vessels involved are considered high-risk. Further research is needed to validate whether this classification is appropriate for these tumors.; In contrast to micrometastases, when LN metastases measure ≥ 1 cm, recurrence rates increase significantly, reaching approximately 32% [87]. For LNs larger than 3 cm, reported recurrence rates range between 27% and 32% (Table 10) [125]. Therefore, consistent with previous guidelines, the K-RSS classifies patients with even a single metastatic LN measuring >3 cm as high-risk [126].; TERT promoter mutations in both PTCs and FTCs have been associated with high recurrence rates. Even in patients with intrathyroidal PTC, where disease-free survival is typically excellent, 10-year disease-free survival decreased from 64.5% to 53.7% when TERT promoter mutations were present [127]. In minimally invasive and encapsulated angioinvasive FTCs harboring TERT promoter mutations, rates of distant metastasis and recurrence were comparable to widely invasive FTCs [128]. A meta-analysis 51 FTC studies further demonstrated significant associations between TERT promoter mutations and tumor recurrence (odds ratio [OR], 4.59; 95% confidence interval [CI], 2.08 to 10.13) as well as poorer disease-specific survival (OR, 9.28; 95% CI, 3.35 to 25.70) [129].; However, these results did not account for coexisting mutations, particularly BRAF^V600E or RAS mutations, which frequently occur alongside TERT promoter mutations. The prognostic impact of isolated TERT promoter mutations remains unclear, especially in the absence of these co-mutations. Similarly, although recurrence rates in PTCs with BRAF^V600E mutations have been reported to range from 5.9% to 34.1%, the high prevalence of BRAF^V600E in the Korean population limits its standalone prognostic significance [130].; In contrast, several retrospective studies have reported significantly worse outcomes when both BRAF^V600E and TERT promoter mutations coexist compared to cases harboring only one or neither mutation. A meta-analysis of 26 studies found that patients with both mutations had a higher risk of tumor recurrence than those with only BRAF^V600E mutations (OR, 4.35; 95% CI, 2.17 to 9.09) or neither mutation (OR, 7.23; 95% CI, 3.37 to 15.51) [131]. Similarly, in DTCs, coexisting RAS and TERT promoter mutations were associated with elevated risks of recurrence (OR, 5.36; 95% CI, 1.20 to 24.02) and disease-specific mortality (OR, 14.75; 95% CI, 1.36 to 167.0) [132].; Therefore, in the K-RSS, patients with concurrent BRAF^V600E and TERT promoter mutations are classified as high-risk, given recurrence rates exceeding 40%. Similarly, cases with coexisting RAS and TERT promoter mutations are also classified as high-risk due to comparable recurrence outcomes.; Thus, postoperative assessment of these mutations may enhance prognostic accuracy. The 2024 KTA guideline recommends postoperative testing for BRAF^V600E, RAS, and TERT promoter mutations to aid prognosis evaluation. In addition to the co-occurrence of TERT promoter mutations with BRAF^V600E or RAS, the presence of two or more high-risk mutations—such as mutations in tumor suppressor genes or genes involved in the phosphoinositide 3-kinase (PI3K)/AKT pathway—is frequently observed in high-grade or dedifferentiated tumors. When these genetic alterations are identified, the K-RSS classifies the patient as high-risk.; Serum Tg measurement, including assessment of anti-Tg antibodies (TgAb), is commonly performed during initial postoperative evaluation. Postoperative Tg levels are influenced by several factors, including the amount of residual normal thyroid and cancer tissue, the Tg-secreting capacity of residual cancer, serum TSH levels at the time of measurement, assay sensitivity, and the elapsed time since thyroidectomy. In particular, the amount of remnant normal thyroid tissue—determined by the extent of surgery and whether RAI remnant ablation was performed—significantly affects both expected Tg ranges and its prognostic utility. Therefore, as shown in a systematic review [133], current evidence is insufficient to support the prognostic utility of serum Tg for predicting recurrence among patients who underwent lobectomy or total thyroidectomy without RAI ablation.; In contrast, after total thyroidectomy and RAI remnant ablation, serum Tg levels more accurately reflect tumor status. A TSH-stimulated Tg level ≥1 to 2 ng/mL has been associated with increased recurrence risk [134-143]. Multivariate analyses have identified elevated Tg as an independent predictor of disease persistence or recurrence [134,135,137,139,140]. High TSH-stimulated Tg levels (≥10 to 30 ng/mL) correlate with lower survival rates, whereas levels ≤1 to 2 ng/mL strongly predict remission [139,144].; Moreover, in cases of distant metastasis, particularly bone metastasis, Tg levels can be markedly elevated. Thus, inappropriately high Tg levels should prompt evaluation for potential distant metastasis. Despite these observations, no consensus currently exists regarding precise cutoff values for stimulated or non-stimulated Tg in predicting recurrence or distant metastasis, complicating the establishment of specific Tg thresholds within an RSS.; Therefore, this guideline does not formally include Tg levels within the K-RSS. Nevertheless, consistent with the M-RSS, which recognizes the clinical significance of elevated Tg levels as indicative of high risk despite undefined thresholds, the K-RSS acknowledges their prognostic implications. Thus, measuring serum Tg (TSH-stimulated or non-stimulated) is recommended to assess residual disease and predict potential recurrence. Prospective studies are necessary to clarify the prognostic role of Tg and establish standardized reference values.
Findings related to lymphatic metastasis not incorporated into K-RSS: Until recently, pathological reports have not clearly distinguished lymphatic and vascular invasion in PTC; instead, they have collectively described these findings as lymphovascular invasion. Furthermore, unlike vascular invasion classification applied to FTC, the extent of lymphatic invasion has not been detailed systematically, hindering precise prognostic assessment. Additionally, extensive lymphatic invasion frequently occurs concurrently with nodal metastasis, making it challenging to isolate its independent prognostic effect. Although recurrence rates associated with lymphovascular invasion have been reported from 16% to 30% [145-147], these limitations impede accurate risk evaluation. Therefore, this guideline does not include lymphatic invasion as an independent factor in recurrence risk stratification.; ENE refers to the invasion of tumor cells beyond the capsule of a metastatic LN into surrounding tissues. ENE is strongly associated with an increased risk of LN recurrence (Table 13). A systematic review of 19 studies reported that ENE negatively affects thyroid cancer prognosis [148]. Similarly, a meta-analysis of 12 studies involving patients with PTC showed that the presence of ENE was associated with a 2.21-fold increase in recurrence risk [149]. A Korean study involving 2,384 PTC patients reported comparable findings, with LN recurrence rates of 2.28% in patients without ENE compared to 13.2% in those with ENE [90].; Recurrence risk also appears to vary depending on the number of LNs exhibiting ENE. Studies have shown that when fewer than three metastatic LNs have ENE, recurrence rates remain relatively low (1% to 4%), but increase significantly—to approximately 32%—when ENE is present in three or more nodes [82,126,148]. Based on these findings, the M-RSS classifies the presence of ENE in three or more LNs as a criterion for the high-risk group.; However, the prognostic impact of ENE has been reported to vary according to the total number of metastatic LNs. Another Korean study found that among patients with five or fewer metastatic LNs and maximum LN size ≤3 cm, the 3-year recurrence rate was 4% without ENE, increasing to 11% when 1 to 3 nodes had ENE [88]. In contrast, for patients with more than five metastatic LNs, 3-year recurrence rates were similar regardless of ENE status: 13% without ENE, 11% with ENE in 1 to 3 nodes, and 15% with ENE in four or more nodes. This suggests that when metastatic LNs exceed five, ENE does not confer significant additional recurrence risk.; Moreover, ENE is rarely observed in cases of LN micrometastasis, which are generally classified as low-risk. Therefore, this guideline does not formally include ENE as a factor in risk stratification. Nevertheless, for intermediate-risk cases—specifically those with five or fewer metastatic LNs—the presence of ENE, although not a stronger predictor than the LN number alone, is associated with an increased recurrence risk (Table 13). Thus, clinical caution is advised in these scenarios, even though ENE is not formally incorporated into the K-RSS. Additionally, longer-term follow-up data are needed to clarify the prognostic impact of ENE.; The LN ratio is defined as the number of metastatic LNs divided by the number of surgically removed LNs. This ratio has not been included in previous clinical guidelines as a risk stratification factor. Recurrence rates according to the LN ratio are summarized in Table 14. A systematic review of nine retrospective studies found that the LN ratio independently predicted locoregional recurrence [150]. Korean studies also report a significant association between LN ratio and recurrence, although proposed cutoff values varied considerably, ranging from 0.22 to 0.65 [151-155]. One study found that patients with an LN ratio of ≥ 0.29 had a recurrence rate of 12.4%, compared to 2.5% in those with a ratio below 0.29 [156]. Another study reported that patients with an LN ratio ≥0.65 had a 10-year recurrence rate of 24.6%, significantly higher than the 1.5% observed in those with a lower ratio [151]. A meta-analysis of 24 studies involving 15,698 thyroid cancer patients similarly showed that a higher LN ratio was associated with decreased disease-free survival [89,90,151-153,156-160].; Although a consistent LN ratio cutoff has not been established and inter-study heterogeneity remains, complicating its direct adoption for risk classification, an elevated LN ratio is significantly associated with increased recurrence risk. Therefore, clinicians should consider it as a supplementary factor when assessing recurrence risk.

CONCLUSIONS

The 2024 KTA guideline presents present an update of the K-RSS, building upon the M-RSS (2015 ATA) through a comprehensive systematic literature review and clinical data analysis. However, it is important to recognize that recurrence rates may vary according to the clinical and pathological characteristics of the study population, surgical extent, and the use of RAI therapy. Furthermore, the interpretation of reported recurrence rates differs across studies due to variations in recurrence definitions, sample sizes, treatment modalities, and follow-up methods and durations. The diverse combinations of clinicopathologic risk factors and treatment approaches within each cohort further complicate efforts to isolate the effects of individual variables on recurrence outcomes.

Moreover, recent advancements in identifying refined pathological risk factors and evolving treatment strategies limit the applicability of data from clinical studies conducted 10 to 20 years ago. In particular, the long-term prognostic implications of newly recognized factors, such as metastatic LN size and ratio, ENE, and specific genetic mutations, remain unclear due to limited evidence. Thus, interpreting recurrence risk estimates provided by current RSSs requires careful consideration of individual patient factors and contexts.

Validation studies across diverse patient populations are necessary to confirm the clinical applicability of the K-RSS. Furthermore, large-scale clinical studies are needed to evaluate long-term recurrence and mortality outcomes based on contemporary pathological criteria and follow-up practices, underscoring the necessity for ongoing guideline updates as new evidence emerges.

Importantly, it should not be overlooked that clinical decisions regarding treatment strategies, such as completion thyroidectomy or adjuvant RAI therapy, should not rely solely on RSS-defined risk groupings. Instead, these decisions must integrate comprehensive assessments of multiple factors, including the estimated recurrence risk, potential treatment-related complications, costs, and patient-specific characteristics and preferences. Determining the appropriate recurrence risk threshold for adjuvant therapy consideration requires a balanced, individualized approach incorporating clinical judgment and shared decision-making.

Supplementary Material

Supplemental Table S1.

Levels of Recommendation in the Korean Thyroid Association Clinical Management Guidelines

enm-2025-2465-Supplemental-Table-S1.pdf

Article information

CONFLICTS OF INTEREST

Young Joo Park is the editor-in-chief, and Eun Kyung Lee is an associate editor of the journal; however, they were not involved in the peer reviewer selection, evaluation, or editorial decision process regarding this article. No other potential conflicts of interest relevant to this article were reported.

ACKNOWLEDGMENTS

This work was supported by the Research fund of National Cancer Center, Republic of Korea (NCC-2112570) and Patient-Centered Clinical Research Coordinating Center (grant number: RS-2024-00398702), funded by the Ministry of Health & Welfare, Republic of Korea. We thank the Korean Cancer Management Guideline Network (KCGN) for the technical support.

This guideline has been originally written in Korean and published in the International Journal of Thyroidology 2024;17(1): 68-96.

Table 1.

Summary of the 2024 Korean Thyroid Association Recommendation

Chapter I.4. Principles of Postoperative Pathological Diagnosis
I.4.1.A. The pathologic diagnosis of differentiated thyroid cancer (DTC) should be rendered in accordance with the World Health Organization (WHO) classification of tumors. [Recommendation level 1]
I.4.3.A. The pathology report should include histological features necessary for American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging and recurrence risk assessment, such as histological subtype, tumor necrosis, mitotic count, vascular invasion (including the number of invaded vessels), lymphatic invasion, number of lymph nodes examined and involved, size of the largest metastatic focus, and extranodal extension. [Recommendation level 1]
I.4.3.B. In papillary thyroid carcinoma (PTC), the histologic subtype should be specified in the pathology report; in particular, it is necessary to identify aggressive subtypes such as tall cell, columnar cell, and hobnail subtypes. [Recommendation level 1]
I.4.3.C. For encapsulated or circumscribed follicular-patterned thyroid carcinomas, the pathology report should clearly state the subtype relevant to risk assessment—the minimally invasive, encapsulated angioinvasive, or widely invasive subtype. [Recommendation level 1]
Chapter I.5.1. Postoperative Initial Disease Status, Recurrence Risk Assessment, and Risk Stratification in DTC
I.5.1.A. Postoperative recurrence risk (initial risk stratification) should be assessed based on residual disease and the likelihood of recurrence. Patients should be categorized into low-, intermediate-, or high-risk groups accordingly. [Recommendation level 3]
I.5.1.B. Thyroid-stimulating hormone (TSH) target levels and additional treatment strategies should be determined based on the initial risk stratification group. [Recommendation level 3]
I.5.2.A. When performing initial risk stratification after surgery, recurrence risk should be evaluated comprehensively, considering the combination of clinical and pathological risk factors rather than relying solely on individual factors. [Recommendation level 3]
I.5.3.A. To assess residual disease and predict potential recurrence, measurement of serum thyroglobulin (either TSH-stimulated or non-stimulated) is recommended after surgery. [Recommendation level 1]
I.5.4.A. For postoperative prognostication, testing for BRAF^V600E, RAS, and telomerase reverse transcriptase (TERT) promoter mutations may be considered. [Recommendation level 3]

Table 2.

The 2024 Korean Thyroid Association Initial Risk Stratification System (K-RSS)^d

Low-risk group (all criteria must be met)	Estimated risk of recurrence 5% or less
	No evidence of local or distant metastases
	No gross or microscopic residual tumor in the thyroid operative bed (R0 resection)
	PTC; excluding aggressive histologic subtypes (tall cell, columnar cell, hobnail, solid/trabecular, and diffuse sclerosing subtypes)
	Minimally invasive subtypes of FTC, OCA, and I-EFVPTC
	PTC ≤2 cm (pT1) or BRAF^V600E-negative PTC <2 cm and ≤4 cm (pT2)
	FTC, OCA, or I-EFVPTC ≤4 cm (pT1-2)^a
	No vascular invasion involving capsular or extratumoral vessels
	Intrathyroidal tumor without ETE or tumor with microscopic ETE
	No uptake outside the thyroid bed on the first post-therapy radioiodine scan (if administered)
	No LN metastases or ≤5 neck LNs with micrometastases (each metastatic focus ≤0.2 cm)
Intermediate-risk group^b	Estimated risk of recurrence >5% and ≤30%
Intermediate-risk group^b	Not categorized as either a low-risk or high-risk group
High-risk group^b (any criteria)	Estimated risk of recurrence greater than 30%
	Gross ETE (pT4), excluding pT3b (limited to strap muscle involvement)
	Poorly differentiated thyroid carcinoma, high-grade differentiated thyroid carcinoma
	Widely invasive subtype of FTC, OCA, and I-EFVPTC
	Extensive vascular invasion (>3 foci of vascular invasion)
	Macroscopic residual tumor (R2 resection)
	Neck LN metastasis >3 cm in maximal diameter
	Presence of two or more high-risk mutations^c, such as BRAF^V600E+TERT promoter or RAS+TERT promoter mutations
	Distant metastases

ETE, extrathyroidal extension; FTC, follicular thyroid carcinoma; K-RSS, Korean Risk Stratification System; I-EFVPTC, invasive encapsulated follicular variant of papillary thyroid carcinoma; LN, lymph node; OCA, oncocytic carcinoma of the thyroid; PTC, papillary thyroid carcinoma; TERT, telomerase reverse transcriptase.

^a Given the elevated risk of recurrence and mortality associated with PTCs (1–4 cm) and minimally invasive FTCs (2–4 cm) harboring TERT promoter mutations, caution is warranted in cases with TERT promoter gene mutations;

^b In the intermediate-risk group, which includes all patients who do not meet the criteria for either low or high risk, the treatment strategy is determined by estimating the recurrence rate based on a comprehensive assessment of multiple clinicopathological factors associated with recurrence risk. Rather than evaluating each factor in isolation, their combined effect on recurrence risk must be considered. Notably, when several intermediate-risk features coexist, the cumulative risk may warrant reclassification to the high-risk category. Relevant factors include extrathyroidal extension, resection margin, vascular invasion, tumor size, multifocality, characteristics of metastatic LNs (such as size, number, or ratio, and extranodal extension), and findings from the first post-radioiodine therapy scan. Detailed recurrence rates are presented in tables in the 2024 KTA Guideline, Chapter I-5 [8];

^c The recurrence risk and risk group may be influenced by both the type of mutated gene and its variant allele frequency;

^d Follicular-patterned tumors include FTC, invasive encapsulated follicular variant of PTC, and oncocytic carcinoma of the thyroid.

Table 3.

Comparison of the 2024 KTA (K-RSS) and 2015 ATA (M-RSS) Risk Stratification Systems

Criteria	M-RSS (2015 ATA)	K-RSS (2024 KTA)	Key distinctions of K-RSS vs. M-RSS
Low-risk group
Recurrence risk	5%–10%^a	5%	Based on 10-year recurrence rate
Recurrence risk	5%–10%^a	5%	Cutoff is defined as 5% but includes slight overruns to avoid overstaging.
PTC
Size	≤1 cm: all	≤2 cm (pT1): all	BRAF^V600E PTC 1–2 cm → low risk (down)
Size	>1, ≤4 cm (1–4 cm): only BRAF^WT	>2, ≤4 cm (pT2): BRAF^WT	4 cm threshold inclusive
Subtype	No aggressive histology (tall cell, columnar, and hobnail subtypes)	No aggressive histology (tall cell, columnar, hobnail, solid and diffuse sclerosing subtypes)	Solid/trabecular and diffuse sclerosing subtypes included in aggressive histology.
Multifocality	Multifocal PTMC	(All multifocal tumors)	Multifocality is not considered in K-RSS.
Encapsulated follicular-patterned thyroid carcinoma
Size	Any size	≤4 cm (pT1, pT2)	>4cm (pT3a) → intermediate risk (up)
Subtype	FTC, minimally invasive	FTC, minimally invasive	Unified FTC/OCA/I-EFVPTC as one group
	FVPTC, encapsulated	OCA, minimally invasive
	FVPTC, encapsulated	I-EFVPTC, minimally invasive
Multifocality	Multifocal PTMC	(All multifocal tumors)	Multifocality is not considered in K-RSS.
ETE	No ETE (intrathyroidal)	No or microscopic ETE	Microscopic ETE → low risk (down)
Vascular invasion	PTC: no vascular invasion	All: no vascular invasion	FTC/OCA/I-EFVPTC with vascular invasion ≤3 foci → intermediate risk (up)
Vascular invasion	FTC: <4 vascular foci	All: no vascular invasion
LN	cN0 or N1 (all <2 mm and ≤5 LNs)	cN0 or pN1 (all ≤2 mm and ≤5 LNs)	2 mm threshold inclusive
Margin	No macroscopic tumor (R0/R1 resection)	No residual tumor (R0 resection)	R1 resection → intermediate risk (up)
Distant metastasis	cM0	cM0	No change
RAI	No uptake outside the thyroid bed	No uptake outside the thyroid bed	No change
Intermediate-risk group
Recurrence risk	(5%–10% to 20%–30%)^a	>5% to 30%	Patients in neither the low- nor high-risk group
			The upper threshold was set at 30%.
			It should be established through comprehensive assessment of all risk factors, with consideration of the heightened risk when they co-occur^b.
Size	BRAF^V600E PTC >1 cm	BRAF^V600E PTC >2 cm	BRAF^V600E PTC 1–2 cm → low risk (down)
	BRAF^WT PTC >4 cm	BRAF^WT PTC >4 cm	FTC/OCA/I-EFVPTC >4 cm → intermediate risk (up)
	BRAF^WT PTC >4 cm	FTC/OCA/I-EFVPTC >4 cm	FTC/OCA/I-EFVPTC >4 cm → intermediate risk (up)
ETE	Microscopic ETE (perithyroidal soft tissue)	Gross ETE confined to perithyroidal soft tissue or strap muscle (pT3b)	Microscopic ETE → low risk (down)
ETE	Microscopic ETE (perithyroidal soft tissue)		Gross ETE confined to perithyroidal soft tissue or strap muscle (pT3b) → intermediate risk (down)
PTMC	Multifocal BRAF^V600E PTMC with ETE (if known)^a	NA	No specific criteria for PTMC (adopt same criteria of ETE)
			Multifocal BRAF^V600E PTMC
			with microscopic ETE → low risk (down)
			with gross ETE (pT3b); no change
			with gross ETE (pT4) → high risk (up)
WBS	Uptake outside thyroid bed	Uptake outside thyroid bed	No change
LN	cN1 or N1>5 LNs and all <3 cm	cN1 or pN1>5 LNs and all ≤3 cm	3 cm threshold inclusive
Subtype	Aggressive histology (tall cell, columnar, and hobnail subtypes)	Aggressive histology (tall cell, columnar, hobnail, solid and diffuse sclerosing subtypes)	Solid/trabecular and diffuse sclerosing subtypes are included in aggressive histology.
Vascular invasion	PTC with any vascular invasion	All thyroid carcinomas with 1–3 vascular foci	FTC/OCA/I-EFVPTC with 1–3 vascular foci → intermediate risk (up)
			PTC with 1–3 vascular foci: no change
			PTC with >3 vascular foci → high risk (up)
High-risk group
Recurrence risk	>20–30^a	>30	Cutoff defined as more than 30
Metastasis	M1	M1	No change
Margin	Incomplete tumor resection (R2)	R2 resection	No change
ETE	Gross ETE (pT3, pT4)	Gross ETE (pT4)	pT3→ intermediate risk (down)
Subtype		HGDTC, PDTC	New description
Subtype		FTC/OCA/I-EFVPTC, widely invasive	New description
Vascular invasion	FTC with VI >4 foci	All tumors with vascular invasion >3 foci (≥4 foci)	The same criterion applies to PTC.
Vascular invasion	FTC with VI >4 foci	All tumors with vascular invasion >3 foci (≥4 foci)	Those with 4 or more vascular foci are included.
LN	pN1 ≥3 cm	pN1 >3 cm	3 cm threshold exclusive
Mutation	pTERT±BRAF^V600E mutation	2 or more high-risk mutations^c (e.g., TERT promoter+BRAF^V600E or RAS mutation)	Single mutations are not classified as high-risk.
Serum thyroglobulin	Inappropriate thyroglobulin level	Not described	Thyroglobulin omitted due to lack of standardized cutoff for high-risk patients^d

ATA, American Thyroid Association; ETE, extrathyroidal extension; FTC, follicular thyroid carcinoma; FVPTC, follicular variant papillary thyroid carcinoma; HGDTC, high-grade differentiated thyroid carcinoma; I-EFVPTC, invasive encapsulated follicular variant of papillary thyroid carcinoma; KRSS, KTA-Risk Stratification System; KTA, Korean Thyroid Association; LN, lymph node; M-RSS, modified Risk Stratification System; NA, not available; OCA, oncocytic carcinoma of the thyroid; PDTC, poorly differentiated thyroid carcinoma; PTC, papillary thyroid carcinoma; PTMC, papillary thyroid microcarcinoma; RAI, radioactive iodine; TERT, telomerase reverse transcriptase; WBS, whole body scan.

^a The cutoff for recurrence risk in the 2015 ATA M-RSS is not clearly defined; those are estimates derived from the clinical study results presented in the text;

^b When multiple risk factors are present, the overall recurrence risk may be higher than when individual risk factors are present alone;

^c High risk mutation: BRAF^V600E+TERT promoter or RAS+TERT promoter mutations. The recurrence risk and risk group may depend on the type and variant allele frequency of the mutated genes. In 1–4 cm PTCs and 2–4 cm minimally invasive FTCs, TERT promoter mutations alone are associated with higher rates of recurrence and death, requiring careful attention when identified;

^d Because no standardized criteria currently exist for defining ‘inappropriate’ serum thyroglobulin levels, this parameter is omitted from the present K-RSS table. However, the guideline text highlights the clinical importance of thyroglobulin measurement, and further research is needed to establish standardized cutoffs, particularly for identifying high-risk patients.

Table 4.

Classification of Differentiated Thyroid Cancer and Their Risk Group Categories in the KTA-Risk Stratification System (K-RSS)

Subtype classification			Papillary thyroid carcinoma			Encapsulated follicular-patterned thyroid carcinoma
Subtype classification			Classic PTC	Encapsulated classic PTC	I-FVPTC	I-EFVPTC		FTC	OCA
Major molecular subtype			BRAF-like	BRAF-like	BRAF-like	RAS-like		RAS-like	RAS-like
Nuclear pattern of PTC			Yes	Yes	Yes	Yes		No	No
Papillary structure and psammoma bodies			Yes	Yes	No	No		No	No
Encapsulation			No	Yes	No	Yes		Yes	Yes
Vascular invasion				Yes or No		Yes or No^a		Yes or No^a	Yes or No^a
Risk group			Papillary thyroid carcinoma			Encapsulated follicular-patterned thyroid carcinoma
	VI	BRAF status	Tumor size			VI	Capsular invasion	Tumor size
	VI	BRAF status	≤ 2 cm	>2 cm, ≤4 cm	>4 cm	VI	Capsular invasion	≤4 cm	>4 cm
	0	BRAF^WT	Low	Low	Intermediate	0	Minimally invasive	Low	Intermediate
		BRAF^V600E	Low	Intermediate	Intermediate
	1–3	All		Intermediate		1–3	No or minimally invasive	Intermediate
	≥4	All		High		≥4	All	High
						All	Widely invasive	High

FTC, follicular thyroid carcinoma; I-EFVPTC, invasive encapsulated follicular variant of papillary thyroid carcinoma; I-FVPTC, infiltrative follicular variant of papillary thyroid carcinoma; KTA, Korean Thyroid Association; K-RSS, KTA-Risk Stratification System; PTC, papillary thyroid carcinoma; OCA, oncocytic carcinoma of the thyroid; VI, vascular invasion.

^a Invasion of either tumor capsule or vessel.

Table 5.

Recurrence Rate of PTC and Minimally Invasive FTC according to Tumor Size

Pathology				Country	Publication year	Enrollment period	No. of patients (each subgroup)	Recurrence rate during follow-up periods, %							Remark (recurrence risk group)	Reference (PMID)
Type	mETE, %	N1, %	M1, %	Country	Publication year	Enrollment period	No. of patients (each subgroup)	Total	≤1 cm (pT1a)	≤2 cm (pT1)	2–4 cm (pT2)	<4 cm (pT1-2)	>4 cm (pT3a)	Median F/U duration, yr	Remark (recurrence risk group)	Reference (PMID)
PTC	0	0	0	Japan	2012	1990–2004	2,591/1,123/251			0.3/1.9/0.4	1.3/4.6–4.8/1.6		1.9/8.1–8.3/3.4	10 YRR	Bed/LN/distant	22068114
PTC	NA	0	0	Italy	2012	2005–2006	213/106	1/7.5	1.7/2.6		1.5/12.1			5 YRR	BRAF^WT/BRAF^V600E	23066120
PTC	100	0	0	Korea	2019	2001–2014	255			3.5/2.1				10 YRR	L/TT	31414221
PTC	42.9	26.8	0	Korea	2017	1997–2015	8,676		1.5/1.7					Mean 5.4	L/TT	27593085
PTC	45.8	58.6	0	Korea	2022	2009–2014	251				4.2/4.6			Mean 8.4	L/TT	35941209
PTC	47.6	54.5	0	Korea	2020	2006–2015	2,902/2,327/227/348	4.6		2.9	8.1		9.2	5 YRR		32081409
PTC	33.0	44.0	4.0	USA	2018	2000–2015	1,720/607/228			0.1/0.2^b	2.6/5.5^b		9.5/33^b	10 YMR	Mortality, all/≥55 yr	30141373
PTC	43.4	35.1	1.4	Korea	2017	1996–2005	2,317/353/70			1.3^b	4.6^b		11.6^b	10 YMR	Mortality	28688696
PTC	NA	49.0	1.7	Korea	2019	1996–2005	1,997/496/96			0.5^b	0.9^b		4.7^b	10 YMR	Mortality	30358515
NI-EFVPTC	0.0	0.0	0	USA	2015	1981–2003	57	0						9.5		25721865
I-EFVPTC	0^a	0^a	0				26	15.0
I-EFVPTC (≥1 cm)	8.0^a	0.0	0	USA	2013	2000–2002	13	0						9.3	Mean size 2.7 cm	23025507
EFVPTC/miFTC/OCA (≥4 cm)	0.0	6.0	0	USA	2023	1995–2021	38/18/8	0/0/0					0/0/0	10 YRR	Mean size 5.0 cm	36884299
FVPTC	7.0	29.0	3.0	USA	2010	1996–1998	34	6.0						9		20497934
miFTC	0	0	0	Japan	2021	2005–2014	221/237					4.2	11.1	10 YRR		33237449
miFTC	0	0	0	Japan	2013	1983–2007	126/166					4.0	9.0	10 YRR		23327839
miFTC	0	0	Yes (NA)	Sweden	2016	1986–2009	4/37/41/17	8.6		0	10.8	9.8	5.9	11.7		26858184
miFTC/OCA	0	0	Yes (NA)	Austria	2009	1963–2006	91/36	6.0				1.1	16.7	7.2 (mean 9.7)		19474675

Adapted from Lee et al. [8].

EFVPTC, encapsulated follicular variant papillary thyroid carcinoma; FTC, follicular thyroid carcinoma; FVPTC, follicular variant papillary thyroid carcinoma; F/U, follow-up; I-EFVPTC, invasive encapsulated follicular variant papillary thyroid carcinoma; L, lobectomy; LN, lymph node; M1, distant metastasis; mETE, microscopic extrathyroidal extension; miFTC, minimally invasive follicular thyroid carcinoma; N1, lymph node metastasis; NA, not available; NI-EFVPTC, noninvasive encapsulated follicular variant papillary thyroid carcinoma; OCA, oncocytic carcinoma of the thyroid; PTC, papillary thyroid carcinoma; TT, total thyroidectomy; YMR, year mortality rate; YRR, year recurrence rate.

^a Only one patient displayed mETE or LN metastasis;

^b Mortality.

Table 6.

Recurrence Rate of FTC according to Vascular Invasion

Pathology		Country	Publication year	Enrollment period	No. of patients (each subgroup)	Recurrence during follow-up periods, %					Remark	Reference (PMID)
Type	M1, %	Country	Publication year	Enrollment period	No. of patients (each subgroup)	VI (+)	VI 1.3	VI ≥2	VI ≥4	Median F/U duration, yr	Remark	Reference (PMID)
eaFTC	0	Japan	2022	2005–2014	251/180/(135)/71	15.9	15.2	24.6	17.9	10 YRR		35169976
eaFTC	0	Korea	2017	1996–2007	157/9		1.9		44.4^a	8.6		27272481
eaFTC	0/7.7	USA	2022	1986–2015	54/52		5.0		23.0	10 YRR		35078345
eaFTC	4.2/17.4	Australia	2023	1990–2018	95/46		6.3		31.7	6.3		36031639
eaFTC	6.6/7.7	Japan	2022	1998–2015	91/26		8.1		19.2	10 YRR		35491160
eaTC	0/20.8	USA	2015	1980–2004	28(6/11/11)/24(4/11/9)		0.0		41.7	6	FTC/OCA/PTC	26482605
						VI (–)		VI (+)
wiFTC	4.1/19.5	Japan	2022	1998–2015	97/41	3.0		20.7		10 YRR		35491160
wiFTC	0	Japan	2023	2005–2016	39			43.2^a		10 YRR		37516689
wiFTC	0	Japan	2021	1998–2016	100/33	8.8		25.8		10 YRR		33746136
wiFTC	10.5	Japan	2021	1998–2016	133	12.7				10 YRR		33746136
						Not defined
wiFTC	29.2	USA	2004	1956–2000	24	37.5				6 (mean 7.5)		15022277
wiFTC/OCA	32.5	Austria	2009	1963–2006	80 (57/23)	37.0				10 YRR		19474675
wiFTC	28.3	Taiwan	2011	1997–2007	145	52.5				Mean 9.6		19596568
wiFTC	45.5	Australia	2011	1983–2008	11	54.0				3.3		21144693
wiFTC	9.4	Korea	2020	1996–2009	33	45.1				10		32981304
wiFTC	33.3	Australia	2023	1990–2018	12	50^a				6.2		36031639

Adapted from Lee et al. [8].

eaFTC, encapsulated angioinvasive follicular thyroid carcinoma; eaTC, encapsulated angioinvasive thyroid cancer; F/U, follow-up; FTC, follicular thyroid carcinoma; M1, distant metastasis; OCA, oncocytic carcinoma of the thyroid; PTC, papillary thyroid carcinoma; VI, vascular invasion; wiFTC, widely invasive follicular thyroid carcinoma; YRR, year recurrence rate.

^a Recurrence with distant metastasis rate.

Table 7.

Recurrence Rate of PTC according to Vascular Invasion

Pathology				Country	Publication year	Enrollment period	No. of patients (each subgroup)	Recurrence during follow-up periods, %		Remark	Reference (PMID)
Type	ETE, %	N1, %	M1, %	Country	Publication year	Enrollment period	No. of patients (each subgroup)	VI (+)	Median F/U duration, yr	Remark	Reference (PMID)
PTC	NA	NA	28.6	USA	2000	1986–2000	31	16.1/19.4	5.5	Local/distant	10722002
PTC/FTC	62.5	80.0	8.3	Japan	2002	1970–1995	120 (109/11)	28.0	4.9 (mean 6.6)		11869709
PTC	23.1	20.5	2.6	Italy	2005	1970–1995	39	20.5	Mean 10		15798466
PTC	25.5	NA	8.5	USA	2015	1986–2003	47	11.5/10.7	Mean 10	Local/distant	25748079
PTC	58.9	70.8	NA	USA	2022	2007–2011	56	17.8	Mean 5		34952686

Adapted from Lee et al. [8].

ETE, extrathyroidal extension; F/U, follow-up; FTC, follicular thyroid carcinoma; M1, presence of distant metastasis; N1, presence of lymph node metastasis; NA, not available; PTC, papillary thyroid carcinoma; VI, vascular invasion.

Table 8.

Recurrence Rate of Differentiated Thyroid Cancer according to the Extent of Extrathyroidal Extension

Pathology			Country	Publication year	Enrollment period	No. of patients (each subgroup)	Recurrence during follow-up periods, %						Remark	Reference (PMID)
Type and size, cm	N1, %	M1, %	Country	Publication year	Enrollment period	No. of patients (each subgroup)	No ETE	mETE	gETE T3b	gETE T4	gETE (T3b+T4)	Median F/U duration, yr	Remark	Reference (PMID)
PTC	0	0	MA	2018	1940–2011	572/1,666	2.2	3.5				7.2	7 studies	29506045
PTC	23.6–55.3	0	MA				6.2	7.0					8 studies	29506045
PTC	NA	NA	MA	2016	2006–2015	5,477/1,797	10.4	10.2				NA	8 studies	28033304
PTC	40	0	USA	2016	1940–2009	319/83/126		9.9			39.0	10 YRR		26514317
PTC	31.8	1.1	USA	2022	1986–2015	5,485/179/216	5.6 (no ETE+mETE)		10.8	23.2		10 YRR		34600743
PTMC	5.2	0.1	Turkey	2024	2010–2022	897/112	2.1	9.8				Mean 5.2		37736822
PTC (all)	NA	0	Italy	2018	2006–2015	387/127	2.3	3.1				9.1		29470826
≤1							1.2	2.5
1–1.5							1.2	2.6
>1.5							10.6	26.0
PTC	54.5	NA	Korea	2020	2006–2015	1,191/1,382/329	2.1	5.6			9.1	7.4		32081409
PTC (1–4)	NA	0	Korea	2022	2005–2012	247/270/78	NA	NA	5.9			7.7	L	35907995
PTC	41.2	NA	Korea	2021	2009–2014	(1,922+1,318)/133	1.8 (no ETE+mETE)		6.0			Mean 8	L	doi.org/10.21593/kjhno/2021.37.2.25
PTC	32.7/59.4/76.4	0/0.1/0.4	Korea	2022	2008–2014	2,411/1,791/250	1.6	4.2			6.80	Mean 10		35625974
PTC	26.2/43.9	NA	Korea	2017	2004–2010	144/191/46	0.7	7.9			34.80	5 YRR	TT only	28222967
PTC	41	0	Korea	2022	2003–2014	1,278/191/346	4.0	5.2	6.1			Mean 10.2	L	36108524
PTC	32.5	0	Korea	2019	2001–2014	257 (85/172)		1.5/3.0				Mean 5	L/TT	31414221
PTC	N1b 3.3	0	Japan	2010	1987–1995	5,166/750		5.6	22.5			Mean 7.6		20824274
PTC	NA	0	Japan	2006	1992–1995	677/356/134	6.5	8.6 (mETE+gETE T3b)		29.9		10 YRR		16411013
PTC	44.9	1.0/3.6/10.9/18.8	Japan	2012	1993–2009	412/265/205	4.0	8.8	29.4	57.5		10 YRR		22402972
PTC	57.7/69.2	NA	Australia	2019	1987–2016	39				23.1		Mean 5		31452204
PTC	No ETE (low 0, intermediate 55.1)/mETE 44.5/gETE 56.9	No ETE (low 0.4, intermediate 3.4)/mETE 2.6/gETE 15.4	Brazil	2020	2012–2018	340/191/65	(3.2/13.5)	13.6	24.6			4	ATA risk group: low/intermediate	32059626
PTC	NA	NA	China	2022	2013–2017	50/177/135		0	11		11	4 YRR		36415538
PTC	45.2/50.0/34.8/25.9	0.2/0.1/1.6/4.1	China	2020	2011–2016	2,300/1,004/371/370	20	21	26	36		2.5		31830859
DTC	no ETE 22.9/gETE st+49.2	no ETE 0.6/gETE st+2.6/gETE 5.0	MA	2020	~2020	13,639	10.70	14.06	16.8–22.9	30.9		NA	6 studies	33102203
DTC	NA	NA	USA	2011	1985–2005	869/115	2	5				10 YRR		22136847
DTC	41.4	0.8	USA	2018	2000–2015	1,291/732/61	1	4	5			5		30022274
DTC	35.1	1.5	Korea	2018	1996–2005	1,362/1,377/261/174	6.30	9.70	10.80	19.70		10 YRR	TT 92, L 8	29663333

Adapted from Lee et al. [8].

ATA, American Thyroid Association; DTC, differentiated thyroid cancer; ETE, extrathyroidal extension; F/U, follow-up; gETE, gross extrathyroidal extension; gETE st+, gross extrathyroidal extension to strap muscle; L, lobectomy; mETE, microscopic extrathyroidal extension; MA, meta-analysis; M1, presence of distant metastasis; NA, not available; N1, presence of lymph node metastasis; PTC, papillary thyroid carcinoma; PTMC, papillary thyroid microcarcinoma; TT, total thyroidectomy; YRR, year recurrence rate.

Table 9.

PTC Recurrence Rate according to Tumor Multifocality

Pathology, %				Country	Publication year	Enrollment period	No. of patients (each subgroup)	Recurrence during follow-up periods, %					Remark	Reference (PMID)
Type and size	mETE	N1	M1					Unifocal		Multifocal		Median F/U duration, yr
Type and size	mETE	N1	M1					≤1 cm	>1 cm	≤1 cm	>1 cm	Median F/U duration, yr
≤1 cm	23.1	0	0	Korea	2019	1999–2012	127/128			3.2/0.8	NA	7.9	L/TT	31264119
≤1 cm vs. >1 cm	48.8	52.4	0	Korea	2015	2007–2009	1,112/376/549/272	1.3	2.4	2.2	6.6	Mean 5.6		25092159
Intrathyroidal PTC	0	0	0	6 countries	2017	2004–2013	967/455	4.2		4.4		4.8		28582521
≤1 cm vs. >1 cm	25.4	34.3	4.5	6 countries	2017	2004-2013	484/297/1,121/699	5.0	16.9	11.8	23.2			28582521
>1 cm	54.0	54.5	5.1	USA	2017	1985–2015	79			NA	6.0	5		28611946
Any size	61.1	42.1	0	Korea	2023	2011–2018	772/(114/372)	2.2		3.0/4.3		5 YRR	Ipsilateral/bilateral multifocal	38001674
Any size	9.2	0	0	USA	2020	1986–2015	619/230	0.5/1.4		0.6/2.2		10 YRR	Unilateral/contralateral lobe	31515125
Any size	61.9	37.8	2.3	Korea	2013	1994–2004	1,423/672	2.0/3.6		2.4/6.4		7	Recurrence/persistence	23135422
Any size	NA	52.6	0	Japan	2022	2010–2017	266/61	3.4		6.6		5.3	Pathological unifocal/multifocal PTC	36510206
Any size	NA	95.0	0	France	2005	1987–1997	46/68	8.0		4.0		Mean 4.7		16030160
Any size	51.5	32.7	0	Korea	2021	2000–2010	299/135	6.0		13.0		10.2		33633983
Any size	47.6	60.7	1	Korea	2019	2006–2015	1,498/892	3.5		7.3		7.7	Gross ETE 15.8	31178204
Any size	26.0	30.1	2.2	Israel	2019	2005–2018	505/534	6.6		12.7		10.1		30799769
Any size	47.6	54.5	0	Korea	2020	2006–2015	1,940/962	2.9		6.4		5 YRR	Gross ETE 11.3	32081409
Any size	51.3	46.7	0	Korea	2017	2006–2012	1,305/623	NA		3.4		7.8	Lateral neck recurrence	28822118
Any size	49.6	58.5	0	China	2013	2006–2007	312/35	0.9		14.3		Mean 4.4		23599804

Adapted from Lee et al. [8].

ETE, extrathyroidal extension; F/U, follow-up; L, lobectomy; M1, presence of distant metastasis; mETE, microscopic extrathyroidal extension; N1, presence of lymph node metastasis; NA, not available; PTC, papillary thyroid carcinoma; TT, total thyroidectomy; YRR, year recurrence rate.

Table 10.

Recurrence Rate of Differentiated Thyroid Cancer according to the Number of Metastatic Lymph Nodes

Pathology	Country	Publication year	Enrollment period	No. of patients (each subgroup)	Recurrence during follow-up periods, %					Remark	Reference (PMID)
Pathology	Country	Publication year	Enrollment period	No. of patients (each subgroup)	0	pN 1-5	pN >5	pN (+)	Median F/U duration, yr	Remark	Reference (PMID)
PTC	Korea	2017	2007–2009	211 (124/87)	3.90			16.3	5 YRR		27574773
PTC	Korea	2021	2009–2014	3,373 (1,984/1,389)	0.70			3.9	Mean 8.1	Lobectomy	doi.org/10.21593/kjhno/2021.37.2.25
PTC ≤2 cm	Korea	2017	2000–2004	2,170 (1,437/1,992/178/733)	3.20	6.2 (≤5)	14.5 (>5)	15.0	10 YRR		27732329
PTC	Korea	2018	2000–2010	382 (300/82)	2.9 (0–1)		6.3 (≥2)		10 YRR		29032663
PTC	Korea	2014	2000–2006	283 (161/122)	NA	6.7 (1–2)	9 (>2)		10 YRR		24006096
PTC >1 cm	Japan	2004	1976–1998	604 (162/366/238/442)	9	8 (0–4)	19 (≥5)	14	10 YRR		14739848
PTC	Korea	2021	2009–2014	3,373 (1,984/[1,185/382]/[204/110])	0.70	3.0/4.5	9.3/9.1		Mean 8.1	All/>1 cm, Lobectomy	doi.org/10.21593/kjhno/2021.37.2.25
DTC	Germany	2023	2012–2018	859 ([148/205]/[80/426])	NA	2.7 /8.3	1.3/10.3		3.9	ENE (–)/(+)	38189969
PTC	France	2005	1987–1997	114 (66/[29/19])	3 (0–5)		7 (6–10)/21 (>10)		Mean 8	After RAI	16030160
PTC	Korea	2018	2006–2012	2,384 (N0–5: 1,853/N >5: 531)	1.20	5.40	12.9 (6–10)/27.7 (>10)		10 YRR		29117854
PTC	Korea	2019	2012–2014	361 ([129/61]/[47/49/75])	4 (ENE 0)/11 (ENE 1–3)		12.7 (ENE 0)/8.1 (ENE 1–3)/12 (ENE >3)		3 YRR	LN ≤3 cm	31025609
PTC	Korea	2021	2010–2016	NA			27.0		8 YRR		33560176
PTC	Review	2012			2 (0–9)	4 (3–8)	19 (7–21)		NA	6 studies	23083442

Adapted from Lee et al. [8].

DTC, differentiated thyroid cancer; ENE, extranodal extension; F/U, follow-up; LN, lymph node. NA, not available; pN, pathologically proven nodal metastasis; PTC, papillary thyroid carcinoma; RAI, radioactive iodine; YRR, year recurrence rate.

Table 11.

Recurrence Rate of Differentiated Thyroid Cancer according to the Size of Metastatic Lymph Nodes

Pathology	Country	Publication year	Enrollment period	No. of patients (each subgroup)	Recurrence during follow-up periods, %				Remark	Reference (PMID)
Pathology	Country	Publication year	Enrollment period	No. of patients (each subgroup)	<0.2 cm	0.2–3 cm	≥3 cm	Median F/U duration, yr	Remark	Reference (PMID)
PTC	France	2008	1995–2000	69 (20/49)	5	NA	32 (>1 cm)	Mean 6.1		18504121
PTC >1 cm	Japan	2004	1976–1998	604 (544/60)	11 (<3 cm)		27	10 YRR		14739848
PTC	Korea	2019	2012–2014	364 ([129/61/47/49/75]/3)	ENE 0	4.0/12.7	67 (>3 cm)	3 YRR	All TT with RAI (LN ≤5/>5)	31025609
					ENE 1–3	11.0/8.1
					ENE >3	12.0
PTC	Korea	2015	2006–2010	136	12.3 (<1.5 cm)		29.6 (≥1.5 cm)	5 YRR		25034816
DTC	Germany	2023	2012–2018	859 ([217/508]/134)	NA	1.8/8.5	13.4	2.9	ENE (–)/(+)	38189969

Adapted from Lee et al. [8].

DTC, differentiated thyroid cancer; ENE, extranodal extension; F/U, follow-up; LN, lymph node; NA, not available ; PTC, papillary thyroid cancer; RAI, radioactive iodine; TT, total thyroidectomy; YRR, year recurrence rate.

Table 12.

Recurrence Rate of Differentiated Thyroid Cancer according to Aggressive Histologic Subtype

Subtype	Country	Publication year	Enrollment period	No. of patients (each subgroup)	Recurrence during follow-up periods, %			Remark	Reference (PMID)
Subtype	Country	Publication year	Enrollment period	No. of patients (each subgroup)	Classic	Aggressive subtype	Median F/U duration, yr	Remark	Reference (PMID)
Tall cell	Spain	1993	NA	85/5	16.5	80.0	NA		8270036
	USA	1994	NA	118/19	3.8	35.3	NA		7977973
	Israel	1995	1954–1993	223/19	9.9	47.4	10.3		7567004
	USA	1998	NA	12/12	8.3	58.3	NA		3337337
	USA	2007	1993–2004	60/49	3.3	8.2	2.3		17696836
	France	2007	1960–1998	503/56	5.4	14.3	7		17097131
	Hong Kong	2008	1960–2000	1,094 Non-tall cell/14	11.9	50.0	8.9		18025951
	USA	2013	2005–2010	58/59	2.0	10.0	1.7/2.5		24238051
	Italy	2013	1999–2011	293/30	8.2	8.3	5.9/7.4		22776915
	14 countries	2016	1978–2011	4,702/239	16.1	27.3	2.4/2.1 (all: 3.4)		26529630
	USA	2016	NA	135/20	15.0	20.0	NA	Historical control	10699809
	MA	2016	NA	1,467/442	6.5	22.2	NA	10 studies	27008708
	Italy	2017	1999–2012	184/72	12.5	20.8	9.7/8.4		28528434
	Korea	2018	2009–2012	282/121	6.0	12.4	4		29875289
	Canada	2019	2001–2015	104/131 (96/35)	7.3	23.7/37.8	5 YRR	≥10%/≥30%	31115855
	USA	2023	1998–2020	94	NA	24/10.4	5 YRR	Local/distant	37159105
	USA	2023	1986–2021	2,080/701	7.6	49.6	5 YRR		37154968
Columnar	USA	1998	1981–1996	16	NA	12.5	Mean 5.8		9477108
	USA	2011	1993–2005	9	NA	22.2	2.1		21358618
	Italy	2017	NA	94	NA	25.4	Mean 5.2		29019044
	Korea	2018	1994–2016	6	NA	33.3	Mean 9		30174490
	Korea	2018	2009–2012	282/18	6.0	27.2	4		29875289
Hobnail	USA	2010	1955–2004	8	NA	37.5	6.4		19956062
	USA	2014	2009–2012	12	NA	33.3	2.2		24417340
	USA	2015	1989–2011	6	NA	83.3	Mean 3.3		25321328
	MA	2017	2010–2017	59	NA	25.4	Mean 5.2	10 studies	29019044
	China	2017	2000–2010	18	NA	5.6	6.0		28423545
	MA	2021	–2020	124	NA	8/36	Mean 4.2	8 studies	33025563
	MA	2022	2012–2020	290	NA	28.0	Mean 3.5	29 studies	35681765
Diffuse sclerosing	MA	2016	1989–2015	64,611/585	11.0	27.2	NA	10 studies	27349273
	Italy	2017	1999–2012	184/54	12.5	31.5	9.7/8.5		28528434
	Portugal	2022	1981–2020	33	NA	9.1	Mean 19.5		34981753
	USA	2023	1986–2021	2,080/86	7.6	11.6	5 YRR		37154968
	Korea	2023	2005–2017	397	NA	11.6	Mean 7.8		37370711
	MA	2023	1989–2021	76,013/874	9.2	25.9	Mean 6	17 studies	36952650
Solid/trabecular	USA	2001	1962–1989	20/20	15.0	15.0	18.7		11717536
	MA	2018		440/52	3.4	13.5	NA	4 studies	29509280
	Turkey	2021	2010–2020	28	NA	7.1	4.4		3838489
	USA/Canada	2022	1982–2021	156	NA	1/4	5/10 YRR		35474588

Adapted from Lee et al. [8].

F/U, follow-up; MA, meta-analysis; NA, not available; YRR, year recurrence rate.

Table 13.

Recurrence Rate of Differentiated Thyroid Cancer according to Extranodal Extension in Metastatic Lymph Nodes

Pathology	Country	Publication year	Enrollment period	No. of patients (each subgroup)	Recurrence during follow-up periods, %						Remark	Reference (PMID)
					ENE (–)		ENE (+)			Median F/U duration, yr
					ENE (–)		Any	1–3	≥4	Median F/U duration, yr
PTC	Korea	2014	2000–2006	283 (250/33)	3.0		8.4			10 YRR		24006096
PTC	Korea	2015	2006–2010	136 (52/84)	9.6		26.2			5 YRR		25034816
PTC	Korea	2018	2006–2012	2,384 (2,014/370)	2.3		13.2			7.8	LN recurrence	29117854
PTC	Korea	2019	2012–2014	361([129/47]/[61/49]/75)	LN ≤3 cm	4/13	NA	11/11	NA/12	3 YRR	LN ≤5/>5	31025609
				3	LN >3 cm	NA	67
PTC	France	2005	1987–1997	114 (72/23/19)	1			4	32	Mean 8		16030160, 23083442
DTC	Germany	2023	2012–2018	859 (228 [148/80]/631 [205/426])	2.2 (2.7/1.3)		9.4 (8.3/10.3)			2.9	LN ≤5/>5	38189969
DTC	MA	2015	–2015	2,939/897	14.6		30.0			NA	17 studies	26493240
DTC	Review	2012					24 (15–32)			NA	2 studies	23083442

Adapted from Lee et al. [8].

DTC, differentiated thyroid cancer; ENE, extranodal extension; F/U, follow-up; LN, lymph node; MA, meta-analysis; NA, not available; PTC, papillary thyroid carcinoma; YRR, year recurrence rate.

Table 14.

Recurrence Rate of Differentiated Thyroid Cancer according to the Ratio of Metastatic Lymph Nodes among Dissected Lymph Nodes

Pathology	Type of ND	Country	Publication year	Enrollment period	No. of patients (each subgroup)	Recurrence during follow-up periods, %					Remark	Reference (PMID)
Pathology	Type of ND	Country	Publication year	Enrollment period	No. of patients (each subgroup)	Cutoff value	No LNM	<Cutoff value	≥Cutoff value	Median F/U duration, yr	Remark	Reference (PMID)
PTC	pCND	Korea	2017	2007–2009	211	0.26	3.9	3.5	20.2	5 YRR		27574773
PTC	pCND	Korea	2023	2007–2017	909 (675/234)	0.29	NA	2.5	12.4	Mean 10.6		37296909
PTC	pCND	Korea	2018	2000–2010	382 (289/93)	0.31	NA	1.5	11.4	10 YRR		29032663
PTC, T2	pCND	Korea	2022	2009–2014	251 (176/75)	0.32	NA	1.1	12.0	Mean 8.4		35941209
PTC	CND	Korea	2014	2000–2006	283 (203/80)	0.65	NA	1.4	24.6	10 YRR		24006096
PTC ≤2 cm	CND	Korea	2017	2000–2004	263/464	0.10	1.0	1.7	14.0	10 YRR	Optimal cutoff in this study	27732329
					337/373	0.19	1.0	2.7	16.2
					379/348	0.20	1.0	3.6	16.2
					438/289	0.30	1.0	5.5	16.0
					532/195	0.40	1.0	6.9	17.1
					582/145	0.50	1.0	8.5	15.3
					625/102	0.60	1.0	8.6	17.4
					661/66	0.70	1.0	8.7	21.8
					687/40	0.80	1.0	9.2	22.1
					703/24	0.90	1.0	9.3	28.3
PTC	CND	Korea	2019	1991–2010	2,424 (1,342 [535/754/53]/1,082 [95/897/90])	0.17857		1.9 (0.8/2.4/7.6)	10.0 (2.1/10.3/15.6)	Mean 9.5	Overall (ATA risk group: low/intermediate/high)	31527831
PTC	CND	Korea	2021	2010–2016	2,409	0.2/0.3/0.4		0.6/0.7/0.9	7.4/9.9/11	8 YRR		33560176
PTC	CND	Korea	2018	2006–2012	2,384 (1,820/564)	0.30	NA	2.5	8.9	7.8	LN recurrence	29117854
PTC >1 cm	CND	Korea	2013	1999–2005	292 (141/46/[56/49])	0.40	3.5	9.1 (all LN ≤0.2 cm)	18.5(>0.2 cm & LNR <0.4 or [≤0.2 cm & LNR >0.4])	8	LN size ≤0.2 cm/0.2 cm	23161752
PTC >1 cm	CND	Korea	2013	1999–2005	292 (141/46/[56/49])	0.40	3.5	9.1 (all LN ≤0.2 cm)	45.2(>0.2 cm & LNR >0.4)	8	LN size ≤0.2 cm/0.2 cm	23161752
PTC	Therapeutic CND+LND	Korea	2015	2006–2010	136	0.26	NA	11.5	31	5 YRR		25034816

Adapted from Lee et al. [8].

ATA, American Thyroid Association; F/U, follow-up; CND, central neck dissection; LN, lymph node; LND, lateral neck dissection; LNM, lymph node metastasis; LNR, lymph node ratio; NA, not available; ND, neck dissection; PTC, papillary thyroid carcinoma; YRR, year recurrence rate.

References

1. Park YJ, Lee EK, Song YS, Koo BS, Kwon H, Kim K, et al. Korean Thyroid Association guidelines on the management of differentiated thyroid cancers; overview and summary 2024. Int J Thyroidol 2024;17:1–20.
2. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 2015 American Thyroid Association Management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid 2016;26:1–133.PubMed PMC
3. Shin SJ, Na HY, Kang HC, Kim SW, Na DG, Park YJ, et al. Korean Thyroid Association guidelines on the management of differentiated thyroid cancers; part I. initial management of differentiated thyroid cancers: chapter 4. pathological diagnosis and staging after thyroidectomy 2024. Int J Thyroidol 2024;17:61–7.Article
4. National Comprehensive Cancer Network. Thyroid carcinoma (version 1.2025) [Internet]. Plymouth Meeting: NCCN; 2025 [cited 2025 Jun 3]. Available from: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1470.
5. American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer, Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009;19:1167–214.Article PubMed
6. Baloch ZW, Asa SL, Barletta JA, Ghossein RA, Juhlin CC, Jung CK, et al. Overview of the 2022 WHO classification of thyroid neoplasms. Endocr Pathol 2022;33:27–63.Article PubMed PDF
7. Jung CK, Bychkov A, Kakudo K. Update from the 2022 World Health Organization classification of thyroid tumors: a standardized diagnostic approach. Endocrinol Metab (Seoul) 2022;37:703–18.Article PubMed PMC PDF
8. Lee EK, Song YS, Kang HC, Kim SW, Na DG, Moon SJ, et al. Korean Thyroid Association guidelines on the management of differentiated thyroid cancers; part I. initial management of differentiated thyroid cancers: chapter 5. evaluation of recurrence risk postoperatively and initial risk stratification in differentiated thyroid cancer 2024. Int J Thyroidol 2024;17:68–96.Article
9. Filetti S, Durante C, Hartl D, Leboulleux S, Locati LD, Newbold K, et al. Thyroid cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2019;30:1856–83.Article PubMed PDF
10. Elisei R, Viola D, Torregrossa L, Giannini R, Romei C, Ugolini C, et al. The BRAF(V600E) mutation is an independent, poor prognostic factor for the outcome of patients with low-risk intrathyroid papillary thyroid carcinoma: single-institution results from a large cohort study. J Clin Endocrinol Metab 2012;97:4390–8.Article PubMed
11. Huang Y, Qu S, Zhu G, Wang F, Liu R, Shen X, et al. BRAF V600E mutation-assisted risk stratification of solitary intrathyroidal papillary thyroid cancer for precision treatment. J Natl Cancer Inst 2018;110:362–70.Article PubMed PMC
12. Ito Y, Kudo T, Kihara M, Takamura Y, Kobayashi K, Miya A, et al. Prognosis of low-risk papillary thyroid carcinoma patients: its relationship with the size of primary tumors. Endocr J 2012;59:119–25.Article PubMed
13. Kim SK, Park I, Woo JW, Lee JH, Choe JH, Kim JH, et al. Total thyroidectomy versus lobectomy in conventional papillary thyroid microcarcinoma: analysis of 8,676 patients at a single institution. Surgery 2017;161:485–92.Article PubMed
14. Kim H, Kim K, Bae JS, Kim JS. Clinical assessment of T2 papillary thyroid carcinoma: a retrospective study conducted at a single tertiary institution. Sci Rep 2022;12:13548.Article PubMed PMC PDF
15. Shin CH, Roh JL, Song DE, Cho KJ, Choi SH, Nam SY, et al. Prognostic value of tumor size and minimal extrathyroidal extension in papillary thyroid carcinoma. Am J Surg 2020;220:925–31.Article PubMed
16. Tam S, Boonsripitayanon M, Amit M, Fellman BM, Li Y, Busaidy NL, et al. Survival in differentiated thyroid cancer: comparing the AJCC cancer staging seventh and eighth editions. Thyroid 2018;28:1301–10.Article PubMed
17. Song E, Lee YM, Oh HS, Jeon MJ, Song DE, Kim TY, et al. A relook at the T stage of differentiated thyroid carcinoma with a focus on gross extrathyroidal extension. Thyroid 2019;29:202–8.Article PubMed
18. Kim TH, Kim YN, Kim HI, Park SY, Choe JH, Kim JH, et al. Prognostic value of the eighth edition AJCC TNM classification for differentiated thyroid carcinoma. Oral Oncol 2017;71:81–6.Article PubMed
19. Gronlund MP, Jensen JS, Hahn CH, Gronhoj C, Buchwald CV. Risk factors for recurrence of follicular thyroid cancer: a systematic review. Thyroid 2021;31:1523–30.PubMed
20. Lo TE, Canto AU, Maningat PD. Risk factors for recurrence in Filipinos with well-differentiated thyroid cancer. Endocrinol Metab (Seoul) 2015;30:543–50.Article PubMed PMC
21. Tzavara I, Vlassopoulou B, Alevizaki C, Koukoulis G, Tzanela M, Koumoussi P, et al. Differentiated thyroid cancer: a retrospective analysis of 832 cases from Greece. Clin Endocrinol (Oxf) 1999;50:643–54.Article PubMed PDF
22. Enomoto K, Enomoto Y, Uchino S, Yamashita H, Noguchi S. Follicular thyroid cancer in children and adolescents: clinicopathologic features, long-term survival, and risk factors for recurrence. Endocr J 2013;60:629–35.Article PubMed
23. Kim WG, Kim TY, Kim TH, Jang HW, Jo YS, Park YJ, et al. Follicular and Hurthle cell carcinoma of the thyroid in iodine-sufficient area: retrospective analysis of Korean multicenter data. Korean J Intern Med 2014;29:325–33.Article PubMed PMC
24. Asari R, Koperek O, Scheuba C, Riss P, Kaserer K, Hoffmann M, et al. Follicular thyroid carcinoma in an iodine-replete endemic goiter region: a prospectively collected, retrospectively analyzed clinical trial. Ann Surg 2009;249:1023–31.PubMed
25. Ghossein R, Ganly I, Tuttle RM, Xu B. Large (>4 cm) intrathyroidal encapsulated well-differentiated follicular cell-derived carcinoma without vascular invasion may have negligible risk of recurrence even when treated with lobectomy alone. Thyroid 2023;33:586–92.Article PubMed PMC
26. Zhang T, He L, Wang Z, Dong W, Sun W, Zhang P, et al. Risk factors for death of follicular thyroid carcinoma: a systematic review and meta-analysis. Endocrine 2023;82:457–66.Article PubMed PMC PDF
27. Yamazaki H, Sugino K, Katoh R, Matsuzu K, Masaki C, Akaishi J, et al. Outcomes for minimally invasive follicular thyroid carcinoma in relation to the change in age stratification in the AJCC 8th edition. Ann Surg Oncol 2021;28:3576–83.Article PubMed PDF
28. Ito Y, Hirokawa M, Masuoka H, Yabuta T, Kihara M, Higashiyama T, et al. Prognostic factors of minimally invasive follicular thyroid carcinoma: extensive vascular invasion significantly affects patient prognosis. Endocr J 2013;60:637–42.Article PubMed
29. Lang W, Choritz H, Hundeshagen H. Risk factors in follicular thyroid carcinomas: a retrospective follow-up study covering a 14-year period with emphasis on morphological findings. Am J Surg Pathol 1986;10:246–55.PubMed
30. Huang CC, Hsueh C, Liu FH, Chao TC, Lin JD. Diagnostic and therapeutic strategies for minimally and widely invasive follicular thyroid carcinomas. Surg Oncol 2011;20:1–6.Article PubMed
31. O’Neill CJ, Vaughan L, Learoyd DL, Sidhu SB, Delbridge LW, Sywak MS. Management of follicular thyroid carcinoma should be individualised based on degree of capsular and vascular invasion. Eur J Surg Oncol 2011;37:181–5.Article PubMed
32. Yamazaki H, Katoh R, Sugino K, Matsuzu K, Masaki C, Akaishi J, et al. Encapsulated angioinvasive follicular thyroid carcinoma: prognostic impact of the extent of vascular invasion. Ann Surg Oncol 2022;29:4236–44.Article PDF
33. Lee YM, Lee YH, Song DE, Kim WB, Sung TY, Yoon JH, et al. Prognostic impact of further treatments on distant metastasis in patients with minimally invasive follicular thyroid carcinoma: verification using inverse probability of treatment weighting. World J Surg 2017;41:138–45.Article PubMed PDF
34. Matsuura D, Yuan A, Wang L, Ranganath R, Adilbay D, Harries V, et al. Follicular and Hurthle cell carcinoma: comparison of clinicopathological features and clinical outcomes. Thyroid 2022;32:245–54.Article PubMed PMC
35. Leong D, Gill AJ, Turchini J, Waller M, Clifton-Bligh R, Glover A, et al. The prognostic impact of extent of vascular invasion in follicular thyroid carcinoma. World J Surg 2023;47:412–20.Article PubMed PDF
36. Ito Y, Hirokawa M, Masuoka H, Higashiyama T, Kihara M, Onoda N, et al. Prognostic factors for follicular thyroid carcinoma: the importance of vascular invasion. Endocr J 2022;69:1149–56.Article PubMed
37. Xu B, Wang L, Tuttle RM, Ganly I, Ghossein R. Prognostic impact of extent of vascular invasion in low-grade encapsulated follicular cell-derived thyroid carcinomas: a clinicopathologic study of 276 cases. Hum Pathol 2015;46:1789–98.Article PubMed PMC
38. Yamazaki H, Sugino K, Katoh R, Matsuzu K, Kitagawa W, Nagahama M, et al. New insights on the importance of the extent of vascular invasion in widely invasive follicular thyroid carcinoma. World J Surg 2023;47:2767–75.Article PubMed PDF
39. Ito Y, Hirokawa M, Fujishima M, Masuoka H, Higashiyama T, Kihara M, et al. Prognostic significance of vascular invasion and cell-proliferation activity in widely invasive follicular carcinoma of the thyroid. Endocr J 2021;68:881–8.Article PubMed
40. D’Avanzo A, Treseler P, Ituarte PH, Wong M, Streja L, Greenspan FS, et al. Follicular thyroid carcinoma: histology and prognosis. Cancer 2004;100:1123–9.Article PubMed
41. Kim HJ, Sung JY, Oh YL, Kim JH, Son YI, Min YK, et al. Association of vascular invasion with increased mortality in patients with minimally invasive follicular thyroid carcinoma but not widely invasive follicular thyroid carcinoma. Head Neck 2014;36:1695–700.Article PubMed
42. Jin M, Kim ES, Kim BH, Kim HK, Yi HS, Jeon MJ, et al. Clinical implication of world health organization classification in patients with follicular thyroid carcinoma in South Korea: a multicenter cohort study. Endocrinol Metab (Seoul) 2020;35:618–27.Article PubMed PMC PDF
43. Gardner RE, Tuttle RM, Burman KD, Haddady S, Truman C, Sparling YH, et al. Prognostic importance of vascular invasion in papillary thyroid carcinoma. Arch Otolaryngol Head Neck Surg 2000;126:309–12.Article PubMed
44. Nishida T, Katayama Si, Tsujimoto M. The clinicopathological significance of histologic vascular invasion in differentiated thyroid carcinoma. Am J Surg 2002;183:80–6.Article PubMed
45. Falvo L, Catania A, D’Andrea V, Marzullo A, Giustiniani MC, De Antoni E. Prognostic importance of histologic vascular invasion in papillary thyroid carcinoma. Ann Surg 2005;241:640–6.Article PubMed PMC
46. Wreesmann VB, Nixon IJ, Rivera M, Katabi N, Palmer F, Ganly I, et al. Prognostic value of vascular invasion in well-differentiated papillary thyroid carcinoma. Thyroid 2015;25:503–8.Article PubMed PMC
47. Reilly J, Faridmoayer E, Lapkus M, Pastewski J, Sun F, Elassar H, et al. Vascular invasion predicts advanced tumor characteristics in papillary thyroid carcinoma. Am J Surg 2022;223:487–91.Article PubMed
48. Abraham E, Roshan D, Tran B, Wykes J, Campbell P, Ebrahimi A. The extent of extrathyroidal extension is a key determinant of prognosis in T4a papillary thyroid cancer. J Surg Oncol 2019;120:1016–22.Article PubMed PDF
49. Amit M, Boonsripitayanon M, Goepfert RP, Tam S, Busaidy NL, Cabanillas ME, et al. Extrathyroidal extension: does strap muscle invasion alone influence recurrence and survival in patients with differentiated thyroid cancer? Ann Surg Oncol 2018;25:3380–8.Article PubMed PDF
50. Heo DB, Piao Y, Lee JH, Ju SH, Yi HS, Kim MS, et al. Completion thyroidectomy may not be required for papillary thyroid carcinoma with multifocality, lymphovascular invasion, extrathyroidal extension to the strap muscles, or five or more central lymph node micrometastasis. Oral Oncol 2022;134:106115.Article PubMed
51. Castagna MG, Forleo R, Maino F, Fralassi N, Barbato F, Palmitesta P, et al. Small papillary thyroid carcinoma with minimal extrathyroidal extension should be managed as ATA low-risk tumor. J Endocrinol Invest 2018;41:1029–35.Article PubMed PDF
52. Danilovic DL, Castroneves LA, Suemoto CK, Elias LO, Soares IC, Camargo RY, et al. Is there a difference between minimal and gross extension into the strap muscles for the risk of recurrence in papillary thyroid carcinomas? Thyroid 2020;30:1008–16.Article PubMed
53. Diker-Cohen T, Hirsch D, Shimon I, Bachar G, Akirov A, Duskin-Bitan H, et al. Impact of minimal extra-thyroid extension in differentiated thyroid cancer: systematic review and meta-analysis. J Clin Endocrinol Metab 2018;103:2100–6.Article PDF
54. Fukushima M, Ito Y, Hirokawa M, Miya A, Shimizu K, Miyauchi A. Prognostic impact of extrathyroid extension and clinical lymph node metastasis in papillary thyroid carcinoma depend on carcinoma size. World J Surg 2010;34:3007–14.Article PubMed PDF
55. Harries V, McGill M, Yuan A, Wang LY, Tuttle RM, Shaha AR, et al. Does macroscopic extrathyroidal extension to the strap muscles alone affect survival in papillary thyroid carcinoma? Surgery 2022;171:1341–7.Article PubMed PMC
56. Hay ID, Johnson TR, Thompson GB, Sebo TJ, Reinalda MS. Minimal extrathyroid extension in papillary thyroid carcinoma does not result in increased rates of either cause-specific mortality or postoperative tumor recurrence. Surgery 2016;159:11–9.Article PubMed
57. He Q, Ji F, Fu X, Li Z, Qiu X. “Micro” extrathyroidal extension in risk stratification for papillary thyroid carcinoma: should it be in the intermediate-risk or high-risk group?: a single-center retrospective study. Cancer Manag Res 2022;14:3181–90.Article PubMed PMC PDF
58. Hotomi M, Sugitani I, Toda K, Kawabata K, Fujimoto Y. A novel definition of extrathyroidal invasion for patients with papillary thyroid carcinoma for predicting prognosis. World J Surg 2012;36:1231–40.Article PubMed PDF
59. Ito Y, Tomoda C, Uruno T, Takamura Y, Miya A, Kobayashi K, et al. Prognostic significance of extrathyroid extension of papillary thyroid carcinoma: massive but not minimal extension affects the relapse-free survival. World J Surg 2006;30:780–6.Article PubMed PDF
60. Jang A, Jin M, Kim WW, Jeon MJ, Sung TY, Song DE, et al. Prognosis of patients with 1-4 cm papillary thyroid cancer who underwent lobectomy: focus on gross extrathyroidal extension invading only the strap muscles. Ann Surg Oncol 2022;29:7835–42.Article PubMed PDF
61. Ji YB, Song CM, Kim D, Sung ES, Lee DW, Chung MS, et al. Efficacy of hemithyroidectomy in papillary thyroid carcinoma with minimal extrathyroidal extension. Eur Arch Otorhinolaryngol 2019;276:3435–42.Article PubMed PDF
62. Kim Y, Kim YS, Bae JS, Kim JS, Kim K. Is gross extrathyroidal extension to strap muscles (T3b) only a risk factor for recurrence in papillary thyroid carcinoma? a propensity score matching study. Cancers (Basel) 2022;14:2370.Article PubMed PMC
63. Li G, Li R, Song L, Chen W, Jiang K, Tang H, et al. Implications of extrathyroidal extension invading only the strap muscles in papillary thyroid carcinomas. Thyroid 2020;30:57–64.Article PubMed
64. Nixon IJ, Ganly I, Patel S, Palmer FL, Whitcher MM, Tuttle RM, et al. The impact of microscopic extrathyroid extension on outcome in patients with clinical T1 and T2 well-differentiated thyroid cancer. Surgery 2011;150:1242–9.Article PubMed
65. Park JS, Chang JW, Liu L, Jung SN, Koo BS. Clinical implications of microscopic extrathyroidal extension in patients with papillary thyroid carcinoma. Oral Oncol 2017;72:183–7.Article PubMed
66. Park SY, Kim HI, Kim JH, Kim JS, Oh YL, Kim SW, et al. Prognostic significance of gross extrathyroidal extension invading only strap muscles in differentiated thyroid carcinoma. Br J Surg 2018;105:1155–62.Article PubMed PDF
67. Yin DT, Yu K, Lu RQ, Li X, Xu J, Lei M. Prognostic impact of minimal extrathyroidal extension in papillary thyroid carcinoma. Medicine (Baltimore) 2016;95:e5794.Article PubMed PMC
68. Zhang L, Liu J, Wang P, Xue S, Li J, Chen G. Impact of gross strap muscle invasion on outcome of differentiated thyroid cancer: systematic review and meta-analysis. Front Oncol 2020;10:1687.Article PubMed PMC
69. Zuhur SS, Aggul H, Avci U, Erol S, Tuna MM, Uysal S, et al. The impact of microscopic extrathyroidal extension on the clinical outcome of classic subtype papillary thyroid microcarcinoma: a multicenter study. Endocrine 2024;83:700–7.Article PubMed PDF
70. Roti E, degli Uberti EC, Bondanelli M, Braverman LE. Thyroid papillary microcarcinoma: a descriptive and meta-analysis study. Eur J Endocrinol 2008;159:659–73.Article PubMed
71. Mazzaferri EL. Management of low-risk differentiated thyroid cancer. Endocr Pract 2007;13:498–512.Article PubMed
72. Kim KJ, Kim SM, Lee YS, Chung WY, Chang HS, Park CS. Prognostic significance of tumor multifocality in papillary thyroid carcinoma and its relationship with primary tumor size: a retrospective study of 2,309 consecutive patients. Ann Surg Oncol 2015;22:125–31.Article PubMed PDF
73. Hartl DM, Guerlain J, Breuskin I, Hadoux J, Baudin E, Al Ghuzlan A, et al. Thyroid lobectomy for low to intermediate risk differentiated thyroid cancer. Cancers (Basel) 2020;12:3282.Article PubMed PMC
74. Choi WR, Roh JL, Gong G, Cho KJ, Choi SH, Nam SY, et al. Multifocality of papillary thyroid carcinoma as a risk factor for disease recurrence. Oral Oncol 2019;94:106–10.Article PubMed
75. Geron Y, Benbassat C, Shteinshneider M, Or K, Markus E, Hirsch D, et al. Multifocality is not an independent prognostic factor in papillary thyroid cancer: a propensity score-matching analysis. Thyroid 2019;29:513–22.Article PubMed
76. Jeon YW, Gwak HG, Lim ST, Schneider J, Suh YJ. Long-term prognosis of unilateral and multifocal papillary thyroid microcarcinoma after unilateral lobectomy versus total thyroidectomy. Ann Surg Oncol 2019;26:2952–8.Article PubMed PDF
77. Kim H, Kwon H. Bilaterality as a risk factor for recurrence in papillary thyroid carcinoma. Cancers (Basel) 2023;15:5414.Article PubMed PMC
78. Kim HJ, Sohn SY, Jang HW, Kim SW, Chung JH. Multifocality, but not bilaterality, is a predictor of disease recurrence/persistence of papillary thyroid carcinoma. World J Surg 2013;37:376–84.Article PubMed PDF
79. Kim JM. The clinical importance of multifocality on tumor recurrence in papillary thyroid carcinoma. Gland Surg 2021;10:273–8.Article PubMed PMC
80. Kim Y, Roh JL, Gong G, Cho KJ, Choi SH, Nam SY, et al. Risk factors for lateral neck recurrence of N0/N1a papillary thyroid cancer. Ann Surg Oncol 2017;24:3609–16.Article PubMed PDF
81. La Greca A, Xu B, Ghossein R, Tuttle RM, Sabra MM. Patients with multifocal macroscopic papillary thyroid carcinoma have a low risk of recurrence at early follow-up after total thyroidectomy and radioactive iodine treatment. Eur Thyroid J 2017;6:31–9.Article PubMed PMC
82. Leboulleux S, Rubino C, Baudin E, Caillou B, Hartl DM, Bidart JM, et al. Prognostic factors for persistent or recurrent disease of papillary thyroid carcinoma with neck lymph node metastases and/or tumor extension beyond the thyroid capsule at initial diagnosis. J Clin Endocrinol Metab 2005;90:5723–9.Article PubMed PDF
83. Li X, Zhao C, Hu D, Yu Y, Gao J, Zhao W, et al. Hemithyroidectomy increases the risk of disease recurrence in patients with ipsilateral multifocal papillary thyroid carcinoma. Oncol Lett 2013;5:1412–6.Article PubMed PMC
84. Omi Y, Haniu K, Kamio H, Fujimoto M, Yoshida Y, Horiuchi K, et al. Pathological multifocality is not a prognosis factor of papillary thyroid carcinoma: a single-center, retrospective study. World J Surg Oncol 2022;20:394.Article PubMed PMC PDF
85. Wang F, Yu X, Shen X, Zhu G, Huang Y, Liu R, et al. The prognostic value of tumor multifocality in clinical outcomes of papillary thyroid cancer. J Clin Endocrinol Metab 2017;102:3241–50.Article PubMed PMC
86. Harries V, Wang LY, McGill M, Xu B, Tuttle RM, Wong RJ, et al. Should multifocality be an indication for completion thyroidectomy in papillary thyroid carcinoma? Surgery 2020;167:10–7.Article PubMed PMC
87. Cranshaw IM, Carnaille B. Micrometastases in thyroid cancer: an important finding? Surg Oncol 2008;17:253–8.Article PubMed
88. Kim HI, Hyeon J, Park SY, Ahn HS, Kim K, Han JM, et al. Impact of extranodal extension on risk stratification in papillary thyroid carcinoma. Thyroid 2019;29:963–70.Article PubMed PMC
89. Hwangbo Y, Kim JM, Park YJ, Lee EK, Lee YJ, Park DJ, et al. Long-term recurrence of small papillary thyroid cancer and its risk factors in a Korean multicenter study. J Clin Endocrinol Metab 2017;102:625–33.PubMed
90. Nam SH, Roh JL, Gong G, Cho KJ, Choi SH, Nam SY, et al. Nodal factors predictive of recurrence after thyroidectomy and neck dissection for papillary thyroid carcinoma. Thyroid 2018;28:88–95.Article PubMed
91. Xu M, Xi Z, Zhao Q, Yang W, Tan J, Yi P, et al. Causal inference between aggressive extrathyroidal extension and survival in papillary thyroid cancer: a propensity score matching and weighting analysis. Front Endocrinol (Lausanne) 2023;14:1149826.Article PubMed PMC
92. Liu Z, Huang Y, Chen S, Hu D, Wang M, Zhou L, et al. Minimal extrathyroidal extension affects the prognosis of differentiated thyroid cancer: is there a need for change in the AJCC classification system? PLoS One 2019;14:e0218171.Article PubMed PMC
93. Lyu YS, Pyo JS, Cho WJ, Kim SY, Kim JH. Clinicopathological significance of papillary thyroid carcinoma located in the isthmus: a meta-analysis. World J Surg 2021;45:2759–68.Article PubMed PDF
94. Park JO, Kim JH, Joo YH, Kim SY, Kim GJ, Kim HB, et al. Guideline for the surgical management of locally invasive differentiated thyroid cancer from the Korean Society of Head and Neck Surgery. Clin Exp Otorhinolaryngol 2023;16:1–19.Article PubMed PMC PDF
95. Sanabria A, Kowalski LP, Nixon IJ, Simo R. Microscopic positive surgical margins in thyroid carcinoma: a proposal for thyroid oncology teams. Langenbecks Arch Surg 2021;406:563–9.Article PubMed PDF
96. Wang LY, Nixon IJ, Patel SG, Palmer FL, Tuttle RM, Shaha A, et al. Operative management of locally advanced, differentiated thyroid cancer. Surgery 2016;160:738–46.Article PubMed PMC
97. Sanabria A, Rojas A, Arevalo J, Kowalski LP, Nixon I. Microscopically positive surgical margins and local recurrence in thyroid cancer: a meta-analysis. Eur J Surg Oncol 2019;45:1310–6.Article PubMed
98. Mercado CE, Drew PA, Morris CG, Dziegielewski PT, Mendenhall WM, Amdur RJ. Positive surgical margins in favorable-stage differentiated thyroid cancer. Am J Clin Oncol 2018;41:1168–71.Article PubMed
99. Kluijfhout WP, Pasternak JD, Kwon JS, Lim J, Shen WT, Gosnell JE, et al. Microscopic positive tumor margin does not increase the risk of recurrence in patients with T1-T2 well-differentiated thyroid cancer. Ann Surg Oncol 2016;23:1446–51.Article PubMed PDF
100. Ito Y, Fukushima M, Yabuta T, Tomoda C, Inoue H, Kihara M, et al. Local prognosis of patients with papillary thyroid carcinoma who were intra-operatively diagnosed as having minimal invasion of the trachea: a 17-year experience in a single institute. Asian J Surg 2009;32:102–8.Article PubMed
101. Zimmer D, Plitt G, Prendes B, Ku J, Silver N, Lamarre E, et al. Utilizing dynamic risk stratification in patients with tall cell variant papillary thyroid cancer. Laryngoscope 2023;133:2430–8.Article PubMed
102. Shi X, Liu R, Basolo F, Giannini R, Shen X, Teng D, et al. Differential clinicopathological risk and prognosis of major papillary thyroid cancer variants. J Clin Endocrinol Metab 2016;101:264–74.PubMed
103. Scholfield DW, Fitzgerald CW, Alzumaili B, Eagan A, Xu B, Martinez G, et al. Diffuse sclerosing papillary thyroid carcinoma: clinicopathological characteristics and prognostic implications compared with classic and tall cell papillary thyroid cancer. Ann Surg Oncol 2023;30:4761–70.Article PubMed PMC PDF
104. Russo M, Malandrino P, Moleti M, Vermiglio F, Violi MA, Marturano I, et al. Tall cell and diffuse sclerosing variants of papillary thyroid cancer: outcome and predicting value of risk stratification methods. J Endocrinol Invest 2017;40:1235–41.Article PubMed PDF
105. Regalbuto C, Malandrino P, Frasca F, Pellegriti G, Le Moli R, Vigneri R, et al. The tall cell variant of papillary thyroid carcinoma: clinical and pathological features and outcomes. J Endocrinol Invest 2013;36:249–54.PubMed
106. Prendiville S, Burman KD, Ringel MD, Shmookler BM, Deeb ZE, Wolfe K, et al. Tall cell variant: an aggressive form of papillary thyroid carcinoma. Otolaryngol Head Neck Surg 2000;122:352–7.Article PubMed PDF
107. Leung AK, Chow SM, Law SC. Clinical features and outcome of the tall cell variant of papillary thyroid carcinoma. Laryngoscope 2008;118:32–8.Article PubMed
108. Bongers PJ, Kluijfhout WP, Verzijl R, Lustgarten M, Vermeer M, Goldstein DP, et al. Papillary thyroid cancers with focal tall cell change are as aggressive as tall cell variants and should not be considered as low-risk disease. Ann Surg Oncol 2019;26:2533–9.Article PubMed PDF
109. Ambrosi F, Righi A, Ricci C, Erickson LA, Lloyd RV, Asioli S. Hobnail variant of papillary thyroid carcinoma: a literature review. Endocr Pathol 2017;28:293–301.Article PubMed PDF
110. Song E, Jeon MJ, Oh HS, Han M, Lee YM, Kim TY, et al. Do aggressive variants of papillary thyroid carcinoma have worse clinical outcome than classic papillary thyroid carcinoma? Eur J Endocrinol 2018;179:135–42.Article PubMed
111. Cho J, Shin JH, Hahn SY, Oh YL. Columnar cell variant of papillary thyroid carcinoma: ultrasonographic and clinical differentiation between the indolent and aggressive types. Korean J Radiol 2018;19:1000–5.Article PubMed PMC PDF
112. Donaldson LB, Yan F, Morgan PF, Kaczmar JM, Fernandes JK, Nguyen SA, et al. Hobnail variant of papillary thyroid carcinoma: a systematic review and meta-analysis. Endocrine 2021;72:27–39.Article PubMed PMC PDF
113. Spyroglou A, Kostopoulos G, Tseleni S, Toulis K, Bramis K, Mastorakos G, et al. Hobnail papillary thyroid carcinoma, a systematic review and meta-analysis. Cancers (Basel) 2022;14:2785.Article PubMed PMC
114. Crayton H, Wu K, Leong D, Bhimani N, Gild M, Glover A. Diffuse sclerosing variant papillary thyroid carcinoma has worse survival than classic papillary thyroid carcinoma: a meta-analysis. Endocr Relat Cancer 2023;30:e220348.Article PubMed
115. Kim SY, Shin SJ, Lee DG, Yun HJ, Kim SM, Chang H, et al. Clinicopathological and genetic characteristics of patients of different ages with diffuse sclerosing variant papillary thyroid carcinoma. Cancers (Basel) 2023;15:3101.Article PubMed PMC
116. Vuong HG, Odate T, Duong UN, Mochizuki K, Nakazawa T, Katoh R, et al. Prognostic importance of solid variant papillary thyroid carcinoma: a systematic review and meta-analysis. Head Neck 2018;40:1588–97.Article PubMed PDF
117. Vural C, Kiraz U, Turan G, Ozkara SK, Sozen M, Cetinarslan B. Solid variant of papillary thyroid carcinoma: an analysis of 28 cases with current literature. Ann Diagn Pathol 2021;52:151737.Article PubMed
118. Xu B, Viswanathan K, Zhang L, Edmund LN, Ganly O, Tuttle RM, et al. The solid variant of papillary thyroid carcinoma: a multi-institutional retrospective study. Histopathology 2022;81:171–82.Article PubMed PDF
119. Nikiforov YE, Erickson LA, Nikiforova MN, Caudill CM, Lloyd RV. Solid variant of papillary thyroid carcinoma: incidence, clinical-pathologic characteristics, molecular analysis, and biologic behavior. Am J Surg Pathol 2001;25:1478–84.PubMed
120. Hescot S, Al Ghuzlan A, Henry T, Sheikh-Alard H, Lamartina L, Borget I, et al. Prognostic of recurrence and survival in poorly differentiated thyroid cancer. Endocr Relat Cancer 2022;29:625–34.Article PubMed
121. Ibrahimpasic T, Ghossein R, Carlson DL, Nixon I, Palmer FL, Shaha AR, et al. Outcomes in patients with poorly differentiated thyroid carcinoma. J Clin Endocrinol Metab 2014;99:1245–52.Article PubMed
122. Ibrahimpasic T, Ghossein R, Shah JP, Ganly I. Poorly differentiated carcinoma of the thyroid gland: current status and future prospects. Thyroid 2019;29:311–21.Article PubMed PMC
123. Lee DY, Won JK, Lee SH, Park DJ, Jung KC, Sung MW, et al. Changes of clinicopathologic characteristics and survival outcomes of anaplastic and poorly differentiated thyroid carcinoma. Thyroid 2016;26:404–13.Article PubMed
124. Tong J, Ruan M, Jin Y, Fu H, Cheng L, Luo Q, et al. Poorly differentiated thyroid carcinoma: a clinician’s perspective. Eur Thyroid J 2022;11:e220021.Article PubMed PMC
125. Sugitani I, Kasai N, Fujimoto Y, Yanagisawa A. A novel classification system for patients with PTC: addition of the new variables of large (3 cm or greater) nodal metastases and reclassification during the follow-up period. Surgery 2004;135:139–48.Article PubMed
126. Randolph GW, Duh QY, Heller KS, LiVolsi VA, Mandel SJ, Steward DL, et al. The prognostic significance of nodal metastases from papillary thyroid carcinoma can be stratified based on the size and number of metastatic lymph nodes, as well as the presence of extranodal extension. Thyroid 2012;22:1144–52.Article PubMed
127. Ebina A, Togashi Y, Baba S, Sato Y, Sakata S, Ishikawa M, et al. TERT promoter mutation and extent of thyroidectomy in patients with 1-4 cm intrathyroidal papillary carcinoma. Cancers (Basel) 2020;12:2115.Article PubMed PMC
128. Park H, Heo J, Ki CS, Shin JH, Oh YL, Son YI, et al. Selection criteria for completion thyroidectomy in follicular thyroid carcinoma using primary tumor size and TERT promoter mutational status. Ann Surg Oncol 2023;30:2916–25.PubMed PMC
129. Yang J, Gong Y, Yan S, Chen H, Qin S, Gong R. Association between TERT promoter mutations and clinical behaviors in differentiated thyroid carcinoma: a systematic review and meta-analysis. Endocrine 2020;67:44–57.Article PubMed PMC PDF
130. Li X, Kwon H. The impact of BRAF mutation on the recurrence of papillary thyroid carcinoma: a meta-analysis. Cancers (Basel) 2020;12:2056.Article PubMed PMC
131. Zhao L, Wang L, Jia X, Hu X, Pang P, Zhao S, et al. The coexistence of genetic mutations in thyroid carcinoma predicts histopathological factors associated with a poor prognosis: a systematic review and network meta-analysis. Front Oncol 2020;10:540238.Article PubMed PMC
132. Song YS, Lim JA, Choi H, Won JK, Moon JH, Cho SW, et al. Prognostic effects of TERT promoter mutations are enhanced by coexistence with BRAF or RAS mutations and strengthen the risk prediction by the ATA or TNM staging system in differentiated thyroid cancer patients. Cancer 2016;122:1370–9.Article PubMed
133. Chou R, Dana T, Brent GA, Goldner W, Haymart M, Leung AM, et al. Serum thyroglobulin measurement following surgery without radioactive iodine for differentiated thyroid cancer: a systematic review. Thyroid 2022;32:613–39.Article PubMed PMC
134. Giovanella L, Ceriani L, Ghelfo A, Keller F. Thyroglobulin assay 4 weeks after thyroidectomy predicts outcome in low-risk papillary thyroid carcinoma. Clin Chem Lab Med 2005;43:843–7.Article PubMed
135. Giovanella L, Ceriani L, Suriano S, Ghelfo A, Maffioli M. Thyroglobulin measurement before rhTSH-aided 131I ablation in detecting metastases from differentiated thyroid carcinoma. Clin Endocrinol (Oxf) 2008;69:659–63.Article PubMed
136. Kim TY, Kim WB, Kim ES, Ryu JS, Yeo JS, Kim SC, et al. Serum thyroglobulin levels at the time of 131I remnant ablation just after thyroidectomy are useful for early prediction of clinical recurrence in low-risk patients with differentiated thyroid carcinoma. J Clin Endocrinol Metab 2005;90:1440–5.PubMed
137. Pelttari H, Valimaki MJ, Loyttyniemi E, Schalin-Jantti C. Post-ablative serum thyroglobulin is an independent predictor of recurrence in low-risk differentiated thyroid carcinoma: a 16-year follow-up study. Eur J Endocrinol 2010;163:757–63.Article PubMed
138. Phan HT, Jager PL, van der Wal JE, Sluiter WJ, Plukker JT, Dierckx RA, et al. The follow-up of patients with differentiated thyroid cancer and undetectable thyroglobulin (Tg) and Tg antibodies during ablation. Eur J Endocrinol 2008;158:77–83.Article PubMed
139. Piccardo A, Arecco F, Puntoni M, Foppiani L, Cabria M, Corvisieri S, et al. Focus on high-risk DTC patients: high postoperative serum thyroglobulin level is a strong predictor of disease persistence and is associated to progression-free survival and overall survival. Clin Nucl Med 2013;38:18–24.PubMed
140. Polachek A, Hirsch D, Tzvetov G, Grozinsky-Glasberg S, Slutski I, Singer J, et al. Prognostic value of post-thyroidectomy thyroglobulin levels in patients with differentiated thyroid cancer. J Endocrinol Invest 2011;34:855–60.PubMed
141. Toubeau M, Touzery C, Arveux P, Chaplain G, Vaillant G, Berriolo A, et al. Predictive value for disease progression of serum thyroglobulin levels measured in the postoperative period and after (131)I ablation therapy in patients with differentiated thyroid cancer. J Nucl Med 2004;45:988–94.PubMed
142. Vaisman A, Orlov S, Yip J, Hu C, Lim T, Dowar M, et al. Application of post-surgical stimulated thyroglobulin for radioiodine remnant ablation selection in low-risk papillary thyroid carcinoma. Head Neck 2010;32:689–98.Article PubMed
143. Webb RC, Howard RS, Stojadinovic A, Gaitonde DY, Wallace MK, Ahmed J, et al. The utility of serum thyroglobulin measurement at the time of remnant ablation for predicting disease-free status in patients with differentiated thyroid cancer: a meta-analysis involving 3947 patients. J Clin Endocrinol Metab 2012;97:2754–63.Article PubMed
144. Heemstra KA, Liu YY, Stokkel M, Kievit J, Corssmit E, Pereira AM, et al. Serum thyroglobulin concentrations predict disease-free remission and death in differentiated thyroid carcinoma. Clin Endocrinol (Oxf) 2007;66:58–64.Article PubMed
145. Mete O, Rotstein L, Asa SL. Controversies in thyroid pathology: thyroid capsule invasion and extrathyroidal extension. Ann Surg Oncol 2010;17:386–91.Article PubMed PDF
146. Kim JM, Kim TY, Kim WB, Gong G, Kim SC, Hong SJ, et al. Lymphovascular invasion is associated with lateral cervical lymph node metastasis in papillary thyroid carcinoma. Laryngoscope 2006;116:2081–5.Article PubMed
147. Lee E, Jung W, Woo JS, Lee JB, Shin BK, Kim HK, et al. Tumor sprouting in papillary thyroid carcinoma is correlated with lymph node metastasis and recurrence. Korean J Pathol 2014;48:117–25.Article PubMed PMC
148. Urken ML, Haser GC, Likhterov I, Wenig BM. The impact of metastatic lymph nodes on risk stratification in differentiated thyroid cancer: have we reached a higher level of understanding? Thyroid 2016;26:481–8.Article PubMed
149. Veronese N, Luchini C, Nottegar A, Kaneko T, Sergi G, Manzato E, et al. Prognostic impact of extra-nodal extension in thyroid cancer: a meta-analysis. J Surg Oncol 2015;112:828–33.Article PubMed
150. Mansour J, Sagiv D, Alon E, Talmi Y. Prognostic value of lymph node ratio in metastatic papillary thyroid carcinoma. J Laryngol Otol 2018;132:8–13.Article PubMed
151. Ryu IS, Song CI, Choi SH, Roh JL, Nam SY, Kim SY. Lymph node ratio of the central compartment is a significant predictor for locoregional recurrence after prophylactic central neck dissection in patients with thyroid papillary carcinoma. Ann Surg Oncol 2014;21:277–83.Article PubMed PDF
152. Lee CW, Roh JL, Gong G, Cho KJ, Choi SH, Nam SY, et al. Risk factors for recurrence of papillary thyroid carcinoma with clinically node-positive lateral neck. Ann Surg Oncol 2015;22:117–24.Article PubMed PDF
153. Jeon MJ, Yoon JH, Han JM, Yim JH, Hong SJ, Song DE, et al. The prognostic value of the metastatic lymph node ratio and maximal metastatic tumor size in pathological N1a papillary thyroid carcinoma. Eur J Endocrinol 2013;168:219–25.Article PubMed
154. Chang YW, Kim HS, Jung SP, Kim HY, Lee JB, Bae JW, et al. Pre-ablation stimulated thyroglobulin is a better predictor of recurrence in pathological N1a papillary thyroid carcinoma than the lymph node ratio. Int J Clin Oncol 2016;21:862–8.Article PubMed PDF
155. Park YM, Wang SG, Shin DH, Kim IJ, Son SM, Lee BJ. Lymph node status of lateral neck compartment in patients with N1b papillary thyroid carcinoma. Acta Otolaryngol 2016;136:319–24.Article PubMed
156. Kang IK, Park J, Bae JS, Kim JS, Kim K. Lymph node ratio predicts recurrence in patients with papillary thyroid carcinoma with low lymph node yield. Cancers (Basel) 2023;15:2947.Article PubMed PMC
157. Zheng CM, Ji YB, Song CM, Ge MH, Tae K. Number of metastatic lymph nodes and ratio of metastatic lymph nodes to total number of retrieved lymph nodes are risk factors for recurrence in patients with clinically node negative papillary thyroid carcinoma. Clin Exp Otorhinolaryngol 2018;11:58–64.Article PubMed PMC PDF
158. Lee YC, Na SY, Park GC, Han JH, Kim SW, Eun YG. Occult lymph node metastasis and risk of regional recurrence in papillary thyroid cancer after bilateral prophylactic central neck dissection: a multi-institutional study. Surgery 2017;161:465–71.Article PubMed
159. Lee J, Lee SG, Kim K, Yim SH, Ryu H, Lee CR, et al. Clinical value of lymph node ratio integration with the 8th edition of the UICC TNM classification and 2015 ATA risk stratification systems for recurrence prediction in papillary thyroid cancer. Sci Rep 2019;9:13361.Article PubMed PMC PDF
160. Hu Y, Wang Z, Dong L, Zhang L, Xiuyang L. The prognostic value of lymph node ratio for thyroid cancer: a meta-analysis. Front Oncol 2024;14:1333094.Article PubMed PMC

Figure & Data

References

Citations

Citations to this article as recorded by

PubReader
ePub Link

Cite

Cite: export Copy Download Format; Close

Download Citation

Download a citation file in RIS format that can be imported by all major citation management software, including EndNote, ProCite, RefWorks, and Reference Manager.

Format:

RIS — For EndNote, ProCite, RefWorks, and most other reference management software
BibTeX — For JabRef, BibDesk, and other BibTeX-specific software

Include:

Citation for the content below
Citation and abstract for the content below

The Initial Risk Stratification System for Differentiated Thyroid Cancer: Key Updates in the 2024 Korean Thyroid Association Guideline

Endocrinol Metab. 2025;40(3):357-384. Published online June 24, 2025

DOI: https://doi.org/10.3803/EnM.2025.2465

XML Download

Related articles

The Initial Risk Stratification System for Differentiated Thyroid Cancer: Key Updates in the 2024 Korean Thyroid Association Guideline

Chapter I.4. Principles of Postoperative Pathological Diagnosis
I.4.1.A. The pathologic diagnosis of differentiated thyroid cancer (DTC) should be rendered in accordance with the World Health Organization (WHO) classification of tumors. [Recommendation level 1]
I.4.3.A. The pathology report should include histological features necessary for American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging and recurrence risk assessment, such as histological subtype, tumor necrosis, mitotic count, vascular invasion (including the number of invaded vessels), lymphatic invasion, number of lymph nodes examined and involved, size of the largest metastatic focus, and extranodal extension. [Recommendation level 1]
I.4.3.B. In papillary thyroid carcinoma (PTC), the histologic subtype should be specified in the pathology report; in particular, it is necessary to identify aggressive subtypes such as tall cell, columnar cell, and hobnail subtypes. [Recommendation level 1]
I.4.3.C. For encapsulated or circumscribed follicular-patterned thyroid carcinomas, the pathology report should clearly state the subtype relevant to risk assessment—the minimally invasive, encapsulated angioinvasive, or widely invasive subtype. [Recommendation level 1]
Chapter I.5.1. Postoperative Initial Disease Status, Recurrence Risk Assessment, and Risk Stratification in DTC
I.5.1.A. Postoperative recurrence risk (initial risk stratification) should be assessed based on residual disease and the likelihood of recurrence. Patients should be categorized into low-, intermediate-, or high-risk groups accordingly. [Recommendation level 3]
I.5.1.B. Thyroid-stimulating hormone (TSH) target levels and additional treatment strategies should be determined based on the initial risk stratification group. [Recommendation level 3]
I.5.2.A. When performing initial risk stratification after surgery, recurrence risk should be evaluated comprehensively, considering the combination of clinical and pathological risk factors rather than relying solely on individual factors. [Recommendation level 3]
I.5.3.A. To assess residual disease and predict potential recurrence, measurement of serum thyroglobulin (either TSH-stimulated or non-stimulated) is recommended after surgery. [Recommendation level 1]
I.5.4.A. For postoperative prognostication, testing for BRAF^V600E, RAS, and telomerase reverse transcriptase (TERT) promoter mutations may be considered. [Recommendation level 3]

Low-risk group (all criteria must be met)	Estimated risk of recurrence 5% or less
	No evidence of local or distant metastases
	No gross or microscopic residual tumor in the thyroid operative bed (R0 resection)
	PTC; excluding aggressive histologic subtypes (tall cell, columnar cell, hobnail, solid/trabecular, and diffuse sclerosing subtypes)
	Minimally invasive subtypes of FTC, OCA, and I-EFVPTC
	PTC ≤2 cm (pT1) or BRAF^V600E-negative PTC <2 cm and ≤4 cm (pT2)
	FTC, OCA, or I-EFVPTC ≤4 cm (pT1-2)^a
	No vascular invasion involving capsular or extratumoral vessels
	Intrathyroidal tumor without ETE or tumor with microscopic ETE
	No uptake outside the thyroid bed on the first post-therapy radioiodine scan (if administered)
	No LN metastases or ≤5 neck LNs with micrometastases (each metastatic focus ≤0.2 cm)
Intermediate-risk group^b	Estimated risk of recurrence >5% and ≤30%
Intermediate-risk group^b	Not categorized as either a low-risk or high-risk group
High-risk group^b (any criteria)	Estimated risk of recurrence greater than 30%
	Gross ETE (pT4), excluding pT3b (limited to strap muscle involvement)
	Poorly differentiated thyroid carcinoma, high-grade differentiated thyroid carcinoma
	Widely invasive subtype of FTC, OCA, and I-EFVPTC
	Extensive vascular invasion (>3 foci of vascular invasion)
	Macroscopic residual tumor (R2 resection)
	Neck LN metastasis >3 cm in maximal diameter
	Presence of two or more high-risk mutations^c, such as BRAF^V600E+TERT promoter or RAS+TERT promoter mutations
	Distant metastases

Criteria	M-RSS (2015 ATA)	K-RSS (2024 KTA)	Key distinctions of K-RSS vs. M-RSS
Low-risk group
Recurrence risk	5%–10%^a	5%	Based on 10-year recurrence rate
Recurrence risk	5%–10%^a	5%	Cutoff is defined as 5% but includes slight overruns to avoid overstaging.
PTC
Size	≤1 cm: all	≤2 cm (pT1): all	BRAF^V600E PTC 1–2 cm → low risk (down)
Size	>1, ≤4 cm (1–4 cm): only BRAF^WT	>2, ≤4 cm (pT2): BRAF^WT	4 cm threshold inclusive
Subtype	No aggressive histology (tall cell, columnar, and hobnail subtypes)	No aggressive histology (tall cell, columnar, hobnail, solid and diffuse sclerosing subtypes)	Solid/trabecular and diffuse sclerosing subtypes included in aggressive histology.
Multifocality	Multifocal PTMC	(All multifocal tumors)	Multifocality is not considered in K-RSS.
Encapsulated follicular-patterned thyroid carcinoma
Size	Any size	≤4 cm (pT1, pT2)	>4cm (pT3a) → intermediate risk (up)
Subtype	FTC, minimally invasive	FTC, minimally invasive	Unified FTC/OCA/I-EFVPTC as one group
	FVPTC, encapsulated	OCA, minimally invasive
	FVPTC, encapsulated	I-EFVPTC, minimally invasive
Multifocality	Multifocal PTMC	(All multifocal tumors)	Multifocality is not considered in K-RSS.
ETE	No ETE (intrathyroidal)	No or microscopic ETE	Microscopic ETE → low risk (down)
Vascular invasion	PTC: no vascular invasion	All: no vascular invasion	FTC/OCA/I-EFVPTC with vascular invasion ≤3 foci → intermediate risk (up)
Vascular invasion	FTC: <4 vascular foci	All: no vascular invasion
LN	cN0 or N1 (all <2 mm and ≤5 LNs)	cN0 or pN1 (all ≤2 mm and ≤5 LNs)	2 mm threshold inclusive
Margin	No macroscopic tumor (R0/R1 resection)	No residual tumor (R0 resection)	R1 resection → intermediate risk (up)
Distant metastasis	cM0	cM0	No change
RAI	No uptake outside the thyroid bed	No uptake outside the thyroid bed	No change
Intermediate-risk group
Recurrence risk	(5%–10% to 20%–30%)^a	>5% to 30%	Patients in neither the low- nor high-risk group
			The upper threshold was set at 30%.
			It should be established through comprehensive assessment of all risk factors, with consideration of the heightened risk when they co-occur^b.
Size	BRAF^V600E PTC >1 cm	BRAF^V600E PTC >2 cm	BRAF^V600E PTC 1–2 cm → low risk (down)
	BRAF^WT PTC >4 cm	BRAF^WT PTC >4 cm	FTC/OCA/I-EFVPTC >4 cm → intermediate risk (up)
	BRAF^WT PTC >4 cm	FTC/OCA/I-EFVPTC >4 cm	FTC/OCA/I-EFVPTC >4 cm → intermediate risk (up)
ETE	Microscopic ETE (perithyroidal soft tissue)	Gross ETE confined to perithyroidal soft tissue or strap muscle (pT3b)	Microscopic ETE → low risk (down)
ETE	Microscopic ETE (perithyroidal soft tissue)		Gross ETE confined to perithyroidal soft tissue or strap muscle (pT3b) → intermediate risk (down)
PTMC	Multifocal BRAF^V600E PTMC with ETE (if known)^a	NA	No specific criteria for PTMC (adopt same criteria of ETE)
			Multifocal BRAF^V600E PTMC
			with microscopic ETE → low risk (down)
			with gross ETE (pT3b); no change
			with gross ETE (pT4) → high risk (up)
WBS	Uptake outside thyroid bed	Uptake outside thyroid bed	No change
LN	cN1 or N1>5 LNs and all <3 cm	cN1 or pN1>5 LNs and all ≤3 cm	3 cm threshold inclusive
Subtype	Aggressive histology (tall cell, columnar, and hobnail subtypes)	Aggressive histology (tall cell, columnar, hobnail, solid and diffuse sclerosing subtypes)	Solid/trabecular and diffuse sclerosing subtypes are included in aggressive histology.
Vascular invasion	PTC with any vascular invasion	All thyroid carcinomas with 1–3 vascular foci	FTC/OCA/I-EFVPTC with 1–3 vascular foci → intermediate risk (up)
			PTC with 1–3 vascular foci: no change
			PTC with >3 vascular foci → high risk (up)
High-risk group
Recurrence risk	>20–30^a	>30	Cutoff defined as more than 30
Metastasis	M1	M1	No change
Margin	Incomplete tumor resection (R2)	R2 resection	No change
ETE	Gross ETE (pT3, pT4)	Gross ETE (pT4)	pT3→ intermediate risk (down)
Subtype		HGDTC, PDTC	New description
Subtype		FTC/OCA/I-EFVPTC, widely invasive	New description
Vascular invasion	FTC with VI >4 foci	All tumors with vascular invasion >3 foci (≥4 foci)	The same criterion applies to PTC.
Vascular invasion	FTC with VI >4 foci	All tumors with vascular invasion >3 foci (≥4 foci)	Those with 4 or more vascular foci are included.
LN	pN1 ≥3 cm	pN1 >3 cm	3 cm threshold exclusive
Mutation	pTERT±BRAF^V600E mutation	2 or more high-risk mutations^c (e.g., TERT promoter+BRAF^V600E or RAS mutation)	Single mutations are not classified as high-risk.
Serum thyroglobulin	Inappropriate thyroglobulin level	Not described	Thyroglobulin omitted due to lack of standardized cutoff for high-risk patients^d

Subtype classification			Papillary thyroid carcinoma			Encapsulated follicular-patterned thyroid carcinoma
Subtype classification			Classic PTC	Encapsulated classic PTC	I-FVPTC	I-EFVPTC		FTC	OCA
Major molecular subtype			BRAF-like	BRAF-like	BRAF-like	RAS-like		RAS-like	RAS-like
Nuclear pattern of PTC			Yes	Yes	Yes	Yes		No	No
Papillary structure and psammoma bodies			Yes	Yes	No	No		No	No
Encapsulation			No	Yes	No	Yes		Yes	Yes
Vascular invasion				Yes or No		Yes or No^a		Yes or No^a	Yes or No^a
Risk group			Papillary thyroid carcinoma			Encapsulated follicular-patterned thyroid carcinoma
	VI	BRAF status	Tumor size			VI	Capsular invasion	Tumor size
	VI	BRAF status	≤ 2 cm	>2 cm, ≤4 cm	>4 cm	VI	Capsular invasion	≤4 cm	>4 cm
	0	BRAF^WT	Low	Low	Intermediate	0	Minimally invasive	Low	Intermediate
		BRAF^V600E	Low	Intermediate	Intermediate
	1–3	All		Intermediate		1–3	No or minimally invasive	Intermediate
	≥4	All		High		≥4	All	High
						All	Widely invasive	High

Pathology				Country	Publication year	Enrollment period	No. of patients (each subgroup)	Recurrence rate during follow-up periods, %							Remark (recurrence risk group)	Reference (PMID)
Type	mETE, %	N1, %	M1, %	Country	Publication year	Enrollment period	No. of patients (each subgroup)	Total	≤1 cm (pT1a)	≤2 cm (pT1)	2–4 cm (pT2)	<4 cm (pT1-2)	>4 cm (pT3a)	Median F/U duration, yr	Remark (recurrence risk group)	Reference (PMID)
PTC	0	0	0	Japan	2012	1990–2004	2,591/1,123/251			0.3/1.9/0.4	1.3/4.6–4.8/1.6		1.9/8.1–8.3/3.4	10 YRR	Bed/LN/distant	22068114
PTC	NA	0	0	Italy	2012	2005–2006	213/106	1/7.5	1.7/2.6		1.5/12.1			5 YRR	BRAF^WT/BRAF^V600E	23066120
PTC	100	0	0	Korea	2019	2001–2014	255			3.5/2.1				10 YRR	L/TT	31414221
PTC	42.9	26.8	0	Korea	2017	1997–2015	8,676		1.5/1.7					Mean 5.4	L/TT	27593085
PTC	45.8	58.6	0	Korea	2022	2009–2014	251				4.2/4.6			Mean 8.4	L/TT	35941209
PTC	47.6	54.5	0	Korea	2020	2006–2015	2,902/2,327/227/348	4.6		2.9	8.1		9.2	5 YRR		32081409
PTC	33.0	44.0	4.0	USA	2018	2000–2015	1,720/607/228			0.1/0.2^b	2.6/5.5^b		9.5/33^b	10 YMR	Mortality, all/≥55 yr	30141373
PTC	43.4	35.1	1.4	Korea	2017	1996–2005	2,317/353/70			1.3^b	4.6^b		11.6^b	10 YMR	Mortality	28688696
PTC	NA	49.0	1.7	Korea	2019	1996–2005	1,997/496/96			0.5^b	0.9^b		4.7^b	10 YMR	Mortality	30358515
NI-EFVPTC	0.0	0.0	0	USA	2015	1981–2003	57	0						9.5		25721865
I-EFVPTC	0^a	0^a	0				26	15.0
I-EFVPTC (≥1 cm)	8.0^a	0.0	0	USA	2013	2000–2002	13	0						9.3	Mean size 2.7 cm	23025507
EFVPTC/miFTC/OCA (≥4 cm)	0.0	6.0	0	USA	2023	1995–2021	38/18/8	0/0/0					0/0/0	10 YRR	Mean size 5.0 cm	36884299
FVPTC	7.0	29.0	3.0	USA	2010	1996–1998	34	6.0						9		20497934
miFTC	0	0	0	Japan	2021	2005–2014	221/237					4.2	11.1	10 YRR		33237449
miFTC	0	0	0	Japan	2013	1983–2007	126/166					4.0	9.0	10 YRR		23327839
miFTC	0	0	Yes (NA)	Sweden	2016	1986–2009	4/37/41/17	8.6		0	10.8	9.8	5.9	11.7		26858184
miFTC/OCA	0	0	Yes (NA)	Austria	2009	1963–2006	91/36	6.0				1.1	16.7	7.2 (mean 9.7)		19474675

Pathology		Country	Publication year	Enrollment period	No. of patients (each subgroup)	Recurrence during follow-up periods, %					Remark	Reference (PMID)
Type	M1, %	Country	Publication year	Enrollment period	No. of patients (each subgroup)	VI (+)	VI 1.3	VI ≥2	VI ≥4	Median F/U duration, yr	Remark	Reference (PMID)
eaFTC	0	Japan	2022	2005–2014	251/180/(135)/71	15.9	15.2	24.6	17.9	10 YRR		35169976
eaFTC	0	Korea	2017	1996–2007	157/9		1.9		44.4^a	8.6		27272481
eaFTC	0/7.7	USA	2022	1986–2015	54/52		5.0		23.0	10 YRR		35078345
eaFTC	4.2/17.4	Australia	2023	1990–2018	95/46		6.3		31.7	6.3		36031639
eaFTC	6.6/7.7	Japan	2022	1998–2015	91/26		8.1		19.2	10 YRR		35491160
eaTC	0/20.8	USA	2015	1980–2004	28(6/11/11)/24(4/11/9)		0.0		41.7	6	FTC/OCA/PTC	26482605
						VI (–)		VI (+)
wiFTC	4.1/19.5	Japan	2022	1998–2015	97/41	3.0		20.7		10 YRR		35491160
wiFTC	0	Japan	2023	2005–2016	39			43.2^a		10 YRR		37516689
wiFTC	0	Japan	2021	1998–2016	100/33	8.8		25.8		10 YRR		33746136
wiFTC	10.5	Japan	2021	1998–2016	133	12.7				10 YRR		33746136
						Not defined
wiFTC	29.2	USA	2004	1956–2000	24	37.5				6 (mean 7.5)		15022277
wiFTC/OCA	32.5	Austria	2009	1963–2006	80 (57/23)	37.0				10 YRR		19474675
wiFTC	28.3	Taiwan	2011	1997–2007	145	52.5				Mean 9.6		19596568
wiFTC	45.5	Australia	2011	1983–2008	11	54.0				3.3		21144693
wiFTC	9.4	Korea	2020	1996–2009	33	45.1				10		32981304
wiFTC	33.3	Australia	2023	1990–2018	12	50^a				6.2		36031639

Pathology				Country	Publication year	Enrollment period	No. of patients (each subgroup)	Recurrence during follow-up periods, %		Remark	Reference (PMID)
Type	ETE, %	N1, %	M1, %	Country	Publication year	Enrollment period	No. of patients (each subgroup)	VI (+)	Median F/U duration, yr	Remark	Reference (PMID)
PTC	NA	NA	28.6	USA	2000	1986–2000	31	16.1/19.4	5.5	Local/distant	10722002
PTC/FTC	62.5	80.0	8.3	Japan	2002	1970–1995	120 (109/11)	28.0	4.9 (mean 6.6)		11869709
PTC	23.1	20.5	2.6	Italy	2005	1970–1995	39	20.5	Mean 10		15798466
PTC	25.5	NA	8.5	USA	2015	1986–2003	47	11.5/10.7	Mean 10	Local/distant	25748079
PTC	58.9	70.8	NA	USA	2022	2007–2011	56	17.8	Mean 5		34952686

Pathology			Country	Publication year	Enrollment period	No. of patients (each subgroup)	Recurrence during follow-up periods, %						Remark	Reference (PMID)
Type and size, cm	N1, %	M1, %	Country	Publication year	Enrollment period	No. of patients (each subgroup)	No ETE	mETE	gETE T3b	gETE T4	gETE (T3b+T4)	Median F/U duration, yr	Remark	Reference (PMID)
PTC	0	0	MA	2018	1940–2011	572/1,666	2.2	3.5				7.2	7 studies	29506045
PTC	23.6–55.3	0	MA				6.2	7.0					8 studies	29506045
PTC	NA	NA	MA	2016	2006–2015	5,477/1,797	10.4	10.2				NA	8 studies	28033304
PTC	40	0	USA	2016	1940–2009	319/83/126		9.9			39.0	10 YRR		26514317
PTC	31.8	1.1	USA	2022	1986–2015	5,485/179/216	5.6 (no ETE+mETE)		10.8	23.2		10 YRR		34600743
PTMC	5.2	0.1	Turkey	2024	2010–2022	897/112	2.1	9.8				Mean 5.2		37736822
PTC (all)	NA	0	Italy	2018	2006–2015	387/127	2.3	3.1				9.1		29470826
≤1							1.2	2.5
1–1.5							1.2	2.6
>1.5							10.6	26.0
PTC	54.5	NA	Korea	2020	2006–2015	1,191/1,382/329	2.1	5.6			9.1	7.4		32081409
PTC (1–4)	NA	0	Korea	2022	2005–2012	247/270/78	NA	NA	5.9			7.7	L	35907995
PTC	41.2	NA	Korea	2021	2009–2014	(1,922+1,318)/133	1.8 (no ETE+mETE)		6.0			Mean 8	L	doi.org/10.21593/kjhno/2021.37.2.25
PTC	32.7/59.4/76.4	0/0.1/0.4	Korea	2022	2008–2014	2,411/1,791/250	1.6	4.2			6.80	Mean 10		35625974
PTC	26.2/43.9	NA	Korea	2017	2004–2010	144/191/46	0.7	7.9			34.80	5 YRR	TT only	28222967
PTC	41	0	Korea	2022	2003–2014	1,278/191/346	4.0	5.2	6.1			Mean 10.2	L	36108524
PTC	32.5	0	Korea	2019	2001–2014	257 (85/172)		1.5/3.0				Mean 5	L/TT	31414221
PTC	N1b 3.3	0	Japan	2010	1987–1995	5,166/750		5.6	22.5			Mean 7.6		20824274
PTC	NA	0	Japan	2006	1992–1995	677/356/134	6.5	8.6 (mETE+gETE T3b)		29.9		10 YRR		16411013
PTC	44.9	1.0/3.6/10.9/18.8	Japan	2012	1993–2009	412/265/205	4.0	8.8	29.4	57.5		10 YRR		22402972
PTC	57.7/69.2	NA	Australia	2019	1987–2016	39				23.1		Mean 5		31452204
PTC	No ETE (low 0, intermediate 55.1)/mETE 44.5/gETE 56.9	No ETE (low 0.4, intermediate 3.4)/mETE 2.6/gETE 15.4	Brazil	2020	2012–2018	340/191/65	(3.2/13.5)	13.6	24.6			4	ATA risk group: low/intermediate	32059626
PTC	NA	NA	China	2022	2013–2017	50/177/135		0	11		11	4 YRR		36415538
PTC	45.2/50.0/34.8/25.9	0.2/0.1/1.6/4.1	China	2020	2011–2016	2,300/1,004/371/370	20	21	26	36		2.5		31830859
DTC	no ETE 22.9/gETE st+49.2	no ETE 0.6/gETE st+2.6/gETE 5.0	MA	2020	~2020	13,639	10.70	14.06	16.8–22.9	30.9		NA	6 studies	33102203
DTC	NA	NA	USA	2011	1985–2005	869/115	2	5				10 YRR		22136847
DTC	41.4	0.8	USA	2018	2000–2015	1,291/732/61	1	4	5			5		30022274
DTC	35.1	1.5	Korea	2018	1996–2005	1,362/1,377/261/174	6.30	9.70	10.80	19.70		10 YRR	TT 92, L 8	29663333

Pathology, %				Country	Publication year	Enrollment period	No. of patients (each subgroup)	Recurrence during follow-up periods, %					Remark	Reference (PMID)
Type and size	mETE	N1	M1					Unifocal		Multifocal		Median F/U duration, yr
Type and size	mETE	N1	M1					≤1 cm	>1 cm	≤1 cm	>1 cm	Median F/U duration, yr
≤1 cm	23.1	0	0	Korea	2019	1999–2012	127/128			3.2/0.8	NA	7.9	L/TT	31264119
≤1 cm vs. >1 cm	48.8	52.4	0	Korea	2015	2007–2009	1,112/376/549/272	1.3	2.4	2.2	6.6	Mean 5.6		25092159
Intrathyroidal PTC	0	0	0	6 countries	2017	2004–2013	967/455	4.2		4.4		4.8		28582521
≤1 cm vs. >1 cm	25.4	34.3	4.5	6 countries	2017	2004-2013	484/297/1,121/699	5.0	16.9	11.8	23.2			28582521
>1 cm	54.0	54.5	5.1	USA	2017	1985–2015	79			NA	6.0	5		28611946
Any size	61.1	42.1	0	Korea	2023	2011–2018	772/(114/372)	2.2		3.0/4.3		5 YRR	Ipsilateral/bilateral multifocal	38001674
Any size	9.2	0	0	USA	2020	1986–2015	619/230	0.5/1.4		0.6/2.2		10 YRR	Unilateral/contralateral lobe	31515125
Any size	61.9	37.8	2.3	Korea	2013	1994–2004	1,423/672	2.0/3.6		2.4/6.4		7	Recurrence/persistence	23135422
Any size	NA	52.6	0	Japan	2022	2010–2017	266/61	3.4		6.6		5.3	Pathological unifocal/multifocal PTC	36510206
Any size	NA	95.0	0	France	2005	1987–1997	46/68	8.0		4.0		Mean 4.7		16030160
Any size	51.5	32.7	0	Korea	2021	2000–2010	299/135	6.0		13.0		10.2		33633983
Any size	47.6	60.7	1	Korea	2019	2006–2015	1,498/892	3.5		7.3		7.7	Gross ETE 15.8	31178204
Any size	26.0	30.1	2.2	Israel	2019	2005–2018	505/534	6.6		12.7		10.1		30799769
Any size	47.6	54.5	0	Korea	2020	2006–2015	1,940/962	2.9		6.4		5 YRR	Gross ETE 11.3	32081409
Any size	51.3	46.7	0	Korea	2017	2006–2012	1,305/623	NA		3.4		7.8	Lateral neck recurrence	28822118
Any size	49.6	58.5	0	China	2013	2006–2007	312/35	0.9		14.3		Mean 4.4		23599804

Pathology	Country	Publication year	Enrollment period	No. of patients (each subgroup)	Recurrence during follow-up periods, %					Remark	Reference (PMID)
Pathology	Country	Publication year	Enrollment period	No. of patients (each subgroup)	0	pN 1-5	pN >5	pN (+)	Median F/U duration, yr	Remark	Reference (PMID)
PTC	Korea	2017	2007–2009	211 (124/87)	3.90			16.3	5 YRR		27574773
PTC	Korea	2021	2009–2014	3,373 (1,984/1,389)	0.70			3.9	Mean 8.1	Lobectomy	doi.org/10.21593/kjhno/2021.37.2.25
PTC ≤2 cm	Korea	2017	2000–2004	2,170 (1,437/1,992/178/733)	3.20	6.2 (≤5)	14.5 (>5)	15.0	10 YRR		27732329
PTC	Korea	2018	2000–2010	382 (300/82)	2.9 (0–1)		6.3 (≥2)		10 YRR		29032663
PTC	Korea	2014	2000–2006	283 (161/122)	NA	6.7 (1–2)	9 (>2)		10 YRR		24006096
PTC >1 cm	Japan	2004	1976–1998	604 (162/366/238/442)	9	8 (0–4)	19 (≥5)	14	10 YRR		14739848
PTC	Korea	2021	2009–2014	3,373 (1,984/[1,185/382]/[204/110])	0.70	3.0/4.5	9.3/9.1		Mean 8.1	All/>1 cm, Lobectomy	doi.org/10.21593/kjhno/2021.37.2.25
DTC	Germany	2023	2012–2018	859 ([148/205]/[80/426])	NA	2.7 /8.3	1.3/10.3		3.9	ENE (–)/(+)	38189969
PTC	France	2005	1987–1997	114 (66/[29/19])	3 (0–5)		7 (6–10)/21 (>10)		Mean 8	After RAI	16030160
PTC	Korea	2018	2006–2012	2,384 (N0–5: 1,853/N >5: 531)	1.20	5.40	12.9 (6–10)/27.7 (>10)		10 YRR		29117854
PTC	Korea	2019	2012–2014	361 ([129/61]/[47/49/75])	4 (ENE 0)/11 (ENE 1–3)		12.7 (ENE 0)/8.1 (ENE 1–3)/12 (ENE >3)		3 YRR	LN ≤3 cm	31025609
PTC	Korea	2021	2010–2016	NA			27.0		8 YRR		33560176
PTC	Review	2012			2 (0–9)	4 (3–8)	19 (7–21)		NA	6 studies	23083442

Pathology	Country	Publication year	Enrollment period	No. of patients (each subgroup)	Recurrence during follow-up periods, %				Remark	Reference (PMID)
Pathology	Country	Publication year	Enrollment period	No. of patients (each subgroup)	<0.2 cm	0.2–3 cm	≥3 cm	Median F/U duration, yr	Remark	Reference (PMID)
PTC	France	2008	1995–2000	69 (20/49)	5	NA	32 (>1 cm)	Mean 6.1		18504121
PTC >1 cm	Japan	2004	1976–1998	604 (544/60)	11 (<3 cm)		27	10 YRR		14739848
PTC	Korea	2019	2012–2014	364 ([129/61/47/49/75]/3)	ENE 0	4.0/12.7	67 (>3 cm)	3 YRR	All TT with RAI (LN ≤5/>5)	31025609
					ENE 1–3	11.0/8.1
					ENE >3	12.0
PTC	Korea	2015	2006–2010	136	12.3 (<1.5 cm)		29.6 (≥1.5 cm)	5 YRR		25034816
DTC	Germany	2023	2012–2018	859 ([217/508]/134)	NA	1.8/8.5	13.4	2.9	ENE (–)/(+)	38189969

Subtype	Country	Publication year	Enrollment period	No. of patients (each subgroup)	Recurrence during follow-up periods, %			Remark	Reference (PMID)
Subtype	Country	Publication year	Enrollment period	No. of patients (each subgroup)	Classic	Aggressive subtype	Median F/U duration, yr	Remark	Reference (PMID)
Tall cell	Spain	1993	NA	85/5	16.5	80.0	NA		8270036
	USA	1994	NA	118/19	3.8	35.3	NA		7977973
	Israel	1995	1954–1993	223/19	9.9	47.4	10.3		7567004
	USA	1998	NA	12/12	8.3	58.3	NA		3337337
	USA	2007	1993–2004	60/49	3.3	8.2	2.3		17696836
	France	2007	1960–1998	503/56	5.4	14.3	7		17097131
	Hong Kong	2008	1960–2000	1,094 Non-tall cell/14	11.9	50.0	8.9		18025951
	USA	2013	2005–2010	58/59	2.0	10.0	1.7/2.5		24238051
	Italy	2013	1999–2011	293/30	8.2	8.3	5.9/7.4		22776915
	14 countries	2016	1978–2011	4,702/239	16.1	27.3	2.4/2.1 (all: 3.4)		26529630
	USA	2016	NA	135/20	15.0	20.0	NA	Historical control	10699809
	MA	2016	NA	1,467/442	6.5	22.2	NA	10 studies	27008708
	Italy	2017	1999–2012	184/72	12.5	20.8	9.7/8.4		28528434
	Korea	2018	2009–2012	282/121	6.0	12.4	4		29875289
	Canada	2019	2001–2015	104/131 (96/35)	7.3	23.7/37.8	5 YRR	≥10%/≥30%	31115855
	USA	2023	1998–2020	94	NA	24/10.4	5 YRR	Local/distant	37159105
	USA	2023	1986–2021	2,080/701	7.6	49.6	5 YRR		37154968
Columnar	USA	1998	1981–1996	16	NA	12.5	Mean 5.8		9477108
	USA	2011	1993–2005	9	NA	22.2	2.1		21358618
	Italy	2017	NA	94	NA	25.4	Mean 5.2		29019044
	Korea	2018	1994–2016	6	NA	33.3	Mean 9		30174490
	Korea	2018	2009–2012	282/18	6.0	27.2	4		29875289
Hobnail	USA	2010	1955–2004	8	NA	37.5	6.4		19956062
	USA	2014	2009–2012	12	NA	33.3	2.2		24417340
	USA	2015	1989–2011	6	NA	83.3	Mean 3.3		25321328
	MA	2017	2010–2017	59	NA	25.4	Mean 5.2	10 studies	29019044
	China	2017	2000–2010	18	NA	5.6	6.0		28423545
	MA	2021	–2020	124	NA	8/36	Mean 4.2	8 studies	33025563
	MA	2022	2012–2020	290	NA	28.0	Mean 3.5	29 studies	35681765
Diffuse sclerosing	MA	2016	1989–2015	64,611/585	11.0	27.2	NA	10 studies	27349273
	Italy	2017	1999–2012	184/54	12.5	31.5	9.7/8.5		28528434
	Portugal	2022	1981–2020	33	NA	9.1	Mean 19.5		34981753
	USA	2023	1986–2021	2,080/86	7.6	11.6	5 YRR		37154968
	Korea	2023	2005–2017	397	NA	11.6	Mean 7.8		37370711
	MA	2023	1989–2021	76,013/874	9.2	25.9	Mean 6	17 studies	36952650
Solid/trabecular	USA	2001	1962–1989	20/20	15.0	15.0	18.7		11717536
	MA	2018		440/52	3.4	13.5	NA	4 studies	29509280
	Turkey	2021	2010–2020	28	NA	7.1	4.4		3838489
	USA/Canada	2022	1982–2021	156	NA	1/4	5/10 YRR		35474588

Pathology	Country	Publication year	Enrollment period	No. of patients (each subgroup)	Recurrence during follow-up periods, %						Remark	Reference (PMID)
					ENE (–)		ENE (+)			Median F/U duration, yr
					ENE (–)		Any	1–3	≥4	Median F/U duration, yr
PTC	Korea	2014	2000–2006	283 (250/33)	3.0		8.4			10 YRR		24006096
PTC	Korea	2015	2006–2010	136 (52/84)	9.6		26.2			5 YRR		25034816
PTC	Korea	2018	2006–2012	2,384 (2,014/370)	2.3		13.2			7.8	LN recurrence	29117854
PTC	Korea	2019	2012–2014	361([129/47]/[61/49]/75)	LN ≤3 cm	4/13	NA	11/11	NA/12	3 YRR	LN ≤5/>5	31025609
				3	LN >3 cm	NA	67
PTC	France	2005	1987–1997	114 (72/23/19)	1			4	32	Mean 8		16030160, 23083442
DTC	Germany	2023	2012–2018	859 (228 [148/80]/631 [205/426])	2.2 (2.7/1.3)		9.4 (8.3/10.3)			2.9	LN ≤5/>5	38189969
DTC	MA	2015	–2015	2,939/897	14.6		30.0			NA	17 studies	26493240
DTC	Review	2012					24 (15–32)			NA	2 studies	23083442

Pathology	Type of ND	Country	Publication year	Enrollment period	No. of patients (each subgroup)	Recurrence during follow-up periods, %					Remark	Reference (PMID)
Pathology	Type of ND	Country	Publication year	Enrollment period	No. of patients (each subgroup)	Cutoff value	No LNM	<Cutoff value	≥Cutoff value	Median F/U duration, yr	Remark	Reference (PMID)
PTC	pCND	Korea	2017	2007–2009	211	0.26	3.9	3.5	20.2	5 YRR		27574773
PTC	pCND	Korea	2023	2007–2017	909 (675/234)	0.29	NA	2.5	12.4	Mean 10.6		37296909
PTC	pCND	Korea	2018	2000–2010	382 (289/93)	0.31	NA	1.5	11.4	10 YRR		29032663
PTC, T2	pCND	Korea	2022	2009–2014	251 (176/75)	0.32	NA	1.1	12.0	Mean 8.4		35941209
PTC	CND	Korea	2014	2000–2006	283 (203/80)	0.65	NA	1.4	24.6	10 YRR		24006096
PTC ≤2 cm	CND	Korea	2017	2000–2004	263/464	0.10	1.0	1.7	14.0	10 YRR	Optimal cutoff in this study	27732329
					337/373	0.19	1.0	2.7	16.2
					379/348	0.20	1.0	3.6	16.2
					438/289	0.30	1.0	5.5	16.0
					532/195	0.40	1.0	6.9	17.1
					582/145	0.50	1.0	8.5	15.3
					625/102	0.60	1.0	8.6	17.4
					661/66	0.70	1.0	8.7	21.8
					687/40	0.80	1.0	9.2	22.1
					703/24	0.90	1.0	9.3	28.3
PTC	CND	Korea	2019	1991–2010	2,424 (1,342 [535/754/53]/1,082 [95/897/90])	0.17857		1.9 (0.8/2.4/7.6)	10.0 (2.1/10.3/15.6)	Mean 9.5	Overall (ATA risk group: low/intermediate/high)	31527831
PTC	CND	Korea	2021	2010–2016	2,409	0.2/0.3/0.4		0.6/0.7/0.9	7.4/9.9/11	8 YRR		33560176
PTC	CND	Korea	2018	2006–2012	2,384 (1,820/564)	0.30	NA	2.5	8.9	7.8	LN recurrence	29117854
PTC >1 cm	CND	Korea	2013	1999–2005	292 (141/46/[56/49])	0.40	3.5	9.1 (all LN ≤0.2 cm)	18.5(>0.2 cm & LNR <0.4 or [≤0.2 cm & LNR >0.4])	8	LN size ≤0.2 cm/0.2 cm	23161752
PTC >1 cm	CND	Korea	2013	1999–2005	292 (141/46/[56/49])	0.40	3.5	9.1 (all LN ≤0.2 cm)	45.2(>0.2 cm & LNR >0.4)	8	LN size ≤0.2 cm/0.2 cm	23161752
PTC	Therapeutic CND+LND	Korea	2015	2006–2010	136	0.26	NA	11.5	31	5 YRR		25034816

Table 1. Summary of the 2024 Korean Thyroid Association Recommendation

Table 2. The 2024 Korean Thyroid Association Initial Risk Stratification System (K-RSS)d

Given the elevated risk of recurrence and mortality associated with PTCs (1–4 cm) and minimally invasive FTCs (2–4 cm) harboring TERT promoter mutations, caution is warranted in cases with TERT promoter gene mutations;

In the intermediate-risk group, which includes all patients who do not meet the criteria for either low or high risk, the treatment strategy is determined by estimating the recurrence rate based on a comprehensive assessment of multiple clinicopathological factors associated with recurrence risk. Rather than evaluating each factor in isolation, their combined effect on recurrence risk must be considered. Notably, when several intermediate-risk features coexist, the cumulative risk may warrant reclassification to the high-risk category. Relevant factors include extrathyroidal extension, resection margin, vascular invasion, tumor size, multifocality, characteristics of metastatic LNs (such as size, number, or ratio, and extranodal extension), and findings from the first post-radioiodine therapy scan. Detailed recurrence rates are presented in tables in the 2024 KTA Guideline, Chapter I-5 [8];

The recurrence risk and risk group may be influenced by both the type of mutated gene and its variant allele frequency;

Follicular-patterned tumors include FTC, invasive encapsulated follicular variant of PTC, and oncocytic carcinoma of the thyroid.

Table 3. Comparison of the 2024 KTA (K-RSS) and 2015 ATA (M-RSS) Risk Stratification Systems

ATA, American Thyroid Association; ETE, extrathyroidal extension; FTC, follicular thyroid carcinoma; FVPTC, follicular variant papillary thyroid carcinoma; HGDTC, high-grade differentiated thyroid carcinoma; I-EFVPTC, invasive encapsulated follicular variant of papillary thyroid carcinoma; KRSS, KTA-Risk Stratification System; KTA, Korean Thyroid Association; LN, lymph node; M-RSS, modified Risk Stratification System; NA, not available; OCA, oncocytic carcinoma of the thyroid; PDTC, poorly differentiated thyroid carcinoma; PTC, papillary thyroid carcinoma; PTMC, papillary thyroid microcarcinoma; RAI, radioactive iodine; TERT, telomerase reverse transcriptase; WBS, whole body scan.

The cutoff for recurrence risk in the 2015 ATA M-RSS is not clearly defined; those are estimates derived from the clinical study results presented in the text;

When multiple risk factors are present, the overall recurrence risk may be higher than when individual risk factors are present alone;

High risk mutation: BRAF^V600E+TERT promoter or RAS+TERT promoter mutations. The recurrence risk and risk group may depend on the type and variant allele frequency of the mutated genes. In 1–4 cm PTCs and 2–4 cm minimally invasive FTCs, TERT promoter mutations alone are associated with higher rates of recurrence and death, requiring careful attention when identified;

Because no standardized criteria currently exist for defining ‘inappropriate’ serum thyroglobulin levels, this parameter is omitted from the present K-RSS table. However, the guideline text highlights the clinical importance of thyroglobulin measurement, and further research is needed to establish standardized cutoffs, particularly for identifying high-risk patients.

Table 4. Classification of Differentiated Thyroid Cancer and Their Risk Group Categories in the KTA-Risk Stratification System (K-RSS)

Invasion of either tumor capsule or vessel.

Table 5. Recurrence Rate of PTC and Minimally Invasive FTC according to Tumor Size

Adapted from Lee et al. [8].

Only one patient displayed mETE or LN metastasis;

Mortality.

Table 6. Recurrence Rate of FTC according to Vascular Invasion

Adapted from Lee et al. [8].

Recurrence with distant metastasis rate.

Table 7. Recurrence Rate of PTC according to Vascular Invasion

Adapted from Lee et al. [8].

Table 8. Recurrence Rate of Differentiated Thyroid Cancer according to the Extent of Extrathyroidal Extension

Adapted from Lee et al. [8].

Table 9. PTC Recurrence Rate according to Tumor Multifocality

Adapted from Lee et al. [8].

Table 10. Recurrence Rate of Differentiated Thyroid Cancer according to the Number of Metastatic Lymph Nodes

Adapted from Lee et al. [8].

Table 11. Recurrence Rate of Differentiated Thyroid Cancer according to the Size of Metastatic Lymph Nodes

Adapted from Lee et al. [8].

Table 12. Recurrence Rate of Differentiated Thyroid Cancer according to Aggressive Histologic Subtype

Adapted from Lee et al. [8].

F/U, follow-up; MA, meta-analysis; NA, not available; YRR, year recurrence rate.

Table 13. Recurrence Rate of Differentiated Thyroid Cancer according to Extranodal Extension in Metastatic Lymph Nodes

Adapted from Lee et al. [8].

DTC, differentiated thyroid cancer; ENE, extranodal extension; F/U, follow-up; LN, lymph node; MA, meta-analysis; NA, not available; PTC, papillary thyroid carcinoma; YRR, year recurrence rate.

Table 14. Recurrence Rate of Differentiated Thyroid Cancer according to the Ratio of Metastatic Lymph Nodes among Dissected Lymph Nodes

Articles

ABSTRACT

INTRODUCTION

KEY DIFFERENCES OF K-RSS (2024 KTA) FROM THE M-RSS (2015 ATA)

EVIDENCE SUMMARY OF THE KTA INITIAL RISK STRATIFICATION SYSTEM (K-RSS)

Tumor size and BRAF mutational status in PTC

Tumor size in encapsulated or circumscribed follicular-patterned thyroid carcinoma

No vascular invasion within the primary tumor

No or minimal extrathyroidal extension

Multifocality

Five or fewer LN micrometastases

Gross ETE confined to strap muscles (pT3b)

Microscopic residual disease (R1 resection)

1-3 foci of vascular invasion in PTC

Aggressive histologic subtypes of PTC

High-grade thyroid carcinoma: HGDTC and PDTC

Gross ETE above strap muscle and incomplete resection

Four or more foci of vascular invasion

Metastatic LN larger than 3 cm

Two or more high-risk mutations

Usefulness of serum thyroglobulin after surgery

Lymphatic invasion in PTC

ENE of metastatic foci in LNs

Ratio of metastatic LNs to dissected LNs

CONCLUSIONS

Supplementary Material

Supplemental Table S1.

Article information

References

Figure & Data

References

Citations

Table 1.

Table 2.

Table 3.

Table 4.

Table 5.

Table 6.

Table 7.

Table 8.

Table 9.

Table 10.

Table 11.

Table 12.

Table 13.

Table 14.