Optimal extent of thyroidectomy in clinically node-negative unilateral papillary thyroid carcinoma >1 cm and ≤4 cm

Introduction

Papillary thyroid carcinoma (PTC) has emerged as the most prevalent form of thyroid malignancy, with incidence rates rapidly increasing (1). Despite this rise, the prognosis for PTC remains highly favorable, with a 10-year survival rate exceeding 90% (2). The primary treatment strategy for PTC involves surgical resection, which may or may not be followed by postoperative radioactive iodine (RAI) ablation.

Surgical options for thyroidectomy are generally categorized into total thyroidectomy and lobectomy. Total thyroidectomy involves the complete removal of thyroid tissue, which can potentially lower the risk of disease recurrence. It also allows for the administration of adjuvant RAI therapy to improve the effectiveness of the primary treatment and facilitates precise postoperative thyroglobulin monitoring, thereby optimizing long-term disease surveillance (3-5). In contrast, thyroid lobectomy is associated with a lower risk of postoperative complications, such as hypoparathyroidism and recurrent laryngeal nerve (RLN) injury (6,7). Additionally, approximately two-thirds of patients who undergo lobectomy may not require lifelong thyroid hormone replacement therapy (8).

The optimal extent of thyroid surgery for PTC remains a topic of significant debate, despite evolving guidelines. The American Thyroid Association (ATA) has modified its recommendations over time. In 2006, the ATA guidelines advocated for total thyroidectomy in most PTC cases (9). However, subsequent research demonstrated a higher recurrence rate among patients with tumors >1 cm who underwent hemithyroidectomy (10), leading to revised 2009 ATA guidelines, which recommended total thyroidectomy for tumors >1 cm but allowed hemithyroidectomy for low-risk patients with tumors ≤1 cm (11). Further studies revealed comparable cancer-related outcomes between total thyroidectomy and lobectomy for tumors measuring 1–4 cm (12,13), prompting the 2015 ATA guidelines to support both surgical options for patients with T1b or T2 tumors without extrathyroidal extension (ETE) or clinical lymph node metastasis (3).

The British Thyroid Association (BTA) has similarly updated its recommendations. The 2007 BTA guidelines recommended total thyroidectomy for tumors ≥1 cm (14), but the 2014 update emphasized individualized decision-making for patients with tumors measuring 1 to 4 cm, provided they did not present high-risk features such as ETE or lymph node involvement (15). The National Comprehensive Cancer Network (NCCN) guidelines have permitted both total thyroidectomy and lobectomy for low-risk PTC tumors measuring 1.1–4.0 cm since 2009 (16), differing from ATA’s 2009 guidance, which favored total thyroidectomy for tumors >1 cm.

Despite these advancements, there remains no uniform consensus on the optimal surgical approach for >1 cm and ≤4 cm PTC, particularly concerning specific subgroups within this category. This study, therefore, aimed to evaluate oncologic outcomes, including recurrence and survival, in patients with clinically node-negative (cN0) 11–40 mm PTC who have undergone either total thyroidectomy or lobectomy. Furthermore, we investigated risk factors associated with recurrence to inform the most effective surgical strategy. We present this article in accordance with the TREND reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-1-561/rc).

Methods

Patients

We retrospectively analyzed 3,258 patients who underwent thyroidectomy at a tertiary university hospital from January 2000 to December 2021. From this initial cohort, we excluded individuals with benign nodules (n=736), non-papillary thyroid cancer types (n=129), and tumors measuring less than 11 mm or greater than 40 mm (n=1,674). Additional exclusion criteria included patients who had concomitant lateral neck dissection, revision or completion thyroidectomy, isthmusectomy, bilateral tumors, clinically positive lymph nodes in the lateral or central compartments, gross invasion into surrounding structures except strap muscles, or distant metastasis (n=316). Following these exclusions, 403 patients with cN0 11–40 mm unilateral PTC remained for inclusion in this study. Of these, 263 (65.3%) patients underwent total thyroidectomy, while 140 (34.7%) had lobectomy. No formal sample size calculation was performed; all eligible patients treated at Hanyang University Hospital during the study period were included in this study. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Institutional Review Board (IRB) of Hanyang University Hospital (IRB No. 2023-11-023) and individual consent for this retrospective analysis was waived.

All patients underwent both ultrasonography (US) and computed tomography (CT) preoperatively and were finally confirmed as PTC postoperatively. cN0 status was defined as the absence of suspicious lymph nodes on US and CT. Suspicious lymph nodes on US and/or CT were defined by established imaging features suggestive of metastasis (e.g., cystic change, microcalcifications, loss of hilum, or abnormal enhancement). The extent of thyroidectomy was determined by various factors, including tumor size, tumor presence in the contralateral lobe, surgeon preference, patient preference, and intraoperative findings such as the presence and extent of ETE and lymph node metastasis. Decisions regarding prophylactic central neck dissection (CND) generally followed the contemporary ATA guidelines or were made based on the surgeon’s judgment.

Postoperative RAI ablation, when indicated, was administered 2–3 months post-surgery, at doses ranging from 30 to 150 mCi. This intervention was considered for patients exhibiting ETE, cervical lymph node metastasis, or high-risk pathologic subtypes. The decision to proceed with RAI ablation was based on disease status as well as physician and patient preferences.

Clinicopathologic variables were extracted from electronic medical records, operative notes, pathology reports, and imaging records using a standardized data collection form. Patient groups were analyzed according to age, sex, primary tumor size, multifocality, lymphovascular invasion, ETE, tumor-node-metastasis (TNM) staging (AJCC 8th edition), thyroidectomy extent, CND extent, postoperative complications, and RAI ablation. ETE was categorized into three groups: no ETE, minimal ETE, and strap muscle invasion, with minimal ETE defined as tumor extension beyond the thyroid capsule.

Recurrence was assessed using physical examinations, neck US, and serum thyroglobulin measurements under either thyroid-stimulating hormone (TSH)-suppressed or -stimulated conditions, conducted every 6–12 months. Recurrence was defined as a newly detected structural abnormality on imaging, confirmed as PTC via fine needle aspiration cytology or core needle biopsy. Follow-up duration was calculated from the date of initial surgery to the date of recurrence or last outpatient visit.

RLN function was evaluated using flexible laryngoscopy performed the day before and the day after surgery. Permanent RLN palsy was defined as vocal fold paralysis persisting for more than six months. Hypoparathyroidism was identified as an intact parathyroid hormone (iPTH) level below 15 pg/mL (Hanyang University Hospital’s lower normal limit), with permanent hypoparathyroidism defined as a duration of more than six months.

Statistical analysis

Categorical variables were analyzed using Fisher’s exact test or the Chi-squared test, as appropriate. Continuous variables were reported as mean with standard deviation, and group comparisons were conducted using either the Mann-Whitney U test or the independent t-test, depending on data distribution. Disease-free survival (DFS) and overall survival (OS) were assessed through the Kaplan-Meier method, with censoring to account for loss to follow-up, withdrawals, and deaths up to the final follow-up date. Propensity score-matched (PSM) analysis using five covariates, including age, sex, tumor size, CND, and follow-up duration, was performed to reduce baseline imbalances between the lobectomy and total thyroidectomy groups. Patients were matched 1:1 between groups, and covariate balance after matching was assessed using standardized mean differences. Differences between Kaplan-Meier survival curves were evaluated using the log-rank test. DFS was defined as the duration from diagnosis to the occurrence of clinically confirmed persistent or relapsing disease or until the last follow-up visit. To estimate hazard ratios (HR) and their 95% confidence intervals (CI) and to identify independent risk factors for disease recurrence, univariate and multivariate Cox proportional hazards models were applied. Statistical analyses were executed using IBM SPSS Statistics, version 27.0 (IBM Corp., Chicago, IL, USA) and R software version 4.2.1 (R Development Core Team, Vienna, Austria) for propensity score matching. A P value of less than 0.05 was considered to denote statistical significance.

Results

Table 1 presents the baseline demographic and clinicopathological characteristics of patients stratified by tumor size. Among the 403 patients studied, 304 (75.4%) were 11–20 mm sized PTC and 99 (24.6%) as 21–40 mm. No significant differences in age or sex distribution were observed between the 11–20 and 21–40 mm groups. However, multiplicity and ETE were significantly more prevalent in the 11–20 mm group than in the 21–40 mm group (P<0.001 and P=0.009, respectively), while the lymph node metastasis rate did not differ between groups. Total thyroidectomy was performed more frequently in the 21–40 mm group (P=0.04). CND was not significantly different across groups, but the rate of postoperative RAI ablation was higher in the 21–40 mm group (P=0.02).

Table 2 summarizes demographic and clinicopathological characteristics by extent of thyroidectomy. Patients undergoing total thyroidectomy were significantly older and demonstrated greater tumor multiplicity, ETE, and larger tumor size compared to those who underwent lobectomy. Additionally, the total thyroidectomy group exhibited higher rates of lymph node metastasis, CND, and postoperative RAI ablation. The total complication rate was significantly higher in the total thyroidectomy group (52.9%) compared to the lobectomy group (21.4%, P<0.001), with a notably higher incidence of transient hypoparathyroidism (41.1% vs. 5.7%, P<0.001), while rates of permanent hypoparathyroidism were not significantly different (1.5% vs. 0%, P=0.14). No significant differences were noted in the rates of transient or permanent RLN injury between two groups.

Subgroup analyses according to tumor size (11–20 vs. 21–40 mm) and thyroidectomy extent (total thyroidectomy vs. lobectomy) were also performed. In patients with 11–20 mm PTC (Table 3), total thyroidectomy was performed in 62.5%, with significantly older age compared to the lobectomy group. Additionally, the total thyroidectomy group showed greater tumor size, lymph node metastasis rates, and higher staging. But rates of ETE were not significantly different. The overall complication rate was markedly elevated in the total thyroidectomy group, particularly for transient hypoparathyroidism (38.4% vs. 2.6%, P<0.001).

In patients with 21–40 mm PTC (Table 4), total thyroidectomy and lobectomy were performed in 78.5% and 21.5% of cases, respectively. There were no significant differences in age, sex, lymphovascular invasion, or presence of ETE between these groups. However, the total thyroidectomy group exhibited significantly higher rate of advanced N classification. The overall complication rate did not significantly differ between two groups (P=0.08). Rate of transient hypoparathyroidism was elevated in total thyroidectomy group (P=0.01). Seroma formation, however, was more common in the lobectomy group (P=0.04).

In the baseline cohort of 403 patients, recurrence was observed in 9 patients (2.2%). Specifically, recurrence occurred in 6 patients (2.0%) within the 11–20 mm group and in 3 patients (3.0%) within the 21–40 mm group, with no statistically significant difference between these recurrence rates (P=0.54). Recurrence sites predominantly involved the lateral compartment lymph nodes (6 cases in the 11–20 mm group and 1 case in the 21–40 mm group), whereas central lymph node recurrence was infrequent, and no cases were noted where recurrence was isolated to the central lymph nodes. Additionally, contralateral thyroid lobe recurrence was documented in 2 patients with 21–40 mm tumors. All nine cases of recurrence occurred in patients with the classic PTC, with no recurrences identified among follicular variant PTC.

When comparing recurrence rates between total thyroidectomy and lobectomy, no significant difference was detected (2.7% vs. 1.4%, respectively; P=0.43). Within the 11–20 mm cohort, recurrence was noted in 3.2% of patients who had undergone total thyroidectomy, with no recurrences reported among those who underwent lobectomy. For the 21–40 mm cohort, recurrence rates were 2.7% following total thyroidectomy and 7.1% following lobectomy, yet this difference did not reach statistical significance (P=0.11).

To mitigate baseline imbalances between the lobectomy and total thyroidectomy groups, we performed PSM analysis using five covariates of age, sex, tumor size, CND, and follow-up duration (Table 5). After PSM, 88 pairs were generated in the lobectomy and total thyroidectomy groups, and major covariates were well balanced. In the PSM cohort, the recurrence rate did not differ between the two groups. However, the overall complication rate was significantly higher in the total thyroidectomy group (49.5% vs. 24.8%, P=0.009), largely driven by a higher rate of transient hypoparathyroidism (39.1% vs. 7.6%, P<0.001), as seen in the baseline cohort before PSM.

PSM subgroup cohorts were also categorized by tumor size: 11–20 mm (total thyroidectomy, n=64; lobectomy, n=68) and 21–40 mm (total thyroidectomy, n=24; lobectomy, n=20). In the 11–20 mm matched cohort, recurrence rate also did not differ between the two groups (3.1% vs. 0%, P=0.23), whereas complications were higher after total thyroidectomy (37.5% vs. 17.6%, P=0.01), mainly attributable to transient hypoparathyroidism (25.0% vs. 2.9%, P<0.001). In the 21–40 mm matched cohort, recurrence was observed only in the lobectomy group (0% vs. 10.0%, P=0.20), and the overall complication rate did not differ significantly between the two groups (45.8% vs. 35.0%, P=0.55).

Kaplan-Meier survival analysis revealed no significant differences in OS or DFS between the 11–20 and 21–40 mm groups (Figure 1). Likewise, comparisons between total thyroidectomy and lobectomy groups did not show significant disparities in OS or DFS (Figure 2). Subgroup analyses stratified by tumor size (11–20 vs. 21–40 mm) also demonstrated no significant differences in OS or DFS between the surgical approaches.

Figure 1 DFS curves for 11–20 and 21–40 mm unilateral PTC. DFS, disease-free survival; PTC, papillary thyroid carcinoma.

Figure 2 DFS curves comparing total thyroidectomy and lobectomy. DFS, disease-free survival.

We further assessed DFS across three subgroups categorized by the degree of ETE: non-ETE, minimal ETE, and strap muscle invasion. DFS did not differ significantly between the non-ETE and minimal ETE groups. However, the strap muscle invasion group had significantly poorer DFS compared to the non-ETE and minimal ETE groups (Figure 3). Stratified analysis by ETE status indicated no significant differences in DFS between total thyroidectomy and lobectomy within the non-ETE group. Similarly, no significant impact on DFS was observed between the surgical extent in the minimal ETE group. Even in the strap muscle invasion subgroup, DFS curves did not differ between total thyroidectomy and lobectomy. However, given the small number of recurrence events, the lack of statistical significance should be interpreted with caution and does not conclusively establish oncologic equivalence.

Figure 3 DFS curves according to ETE, categorized as non-ETE, minimal ETE, and strap muscle invasion. DFS, disease-free survival; ETE, extrathyroidal extension.

Cox regression analysis was conducted to identify recurrence-associated risk factors (Table 6). Strap muscle invasion emerged as the only significant predictor of recurrence in both univariate (HR =6.380, P=0.01) and multivariate analyses (HR =30.802, P=0.004). Age, sex, tumor size, minimal ETE, CND, and the extent of thyroidectomy were not significantly associated with recurrence risk. Subgroup analysis stratified by tumor size also indicated that only strap muscle invasion was a significant risk factor in the 11–20 and 21–40 mm subgroups (HR =6.234, P=0.04, and HR =31.788, P=0.02).

In the PSM cohort, univariate analysis suggested an association between strap muscle invasion and recurrence (HR =21.679, P=0.03), while the extent of thyroidectomy was not associated with recurrence (HR =0.695, P=0.77). Multivariable modeling after matching was not applicable for several covariates due to the sparse event counts.

Discussion

The optimal surgical extent for PTC has remained a subject of extensive debate over the past several decades, despite evolving guidelines and recommendations. This ongoing discourse is primarily driven by the favorable prognosis associated with PTC and persisting uncertainties regarding the impact of total thyroidectomy on OS and DFS.

Several studies have examined patients with T1–T2 tumors, yielding mixed results. Bilimoria et al. investigated 52,173 patients with PTC in the National Cancer Database and found that cases with tumors larger than 1 cm undergoing hemithyroidectomy had a higher recurrence rate (HR =1.15; 95% CI: 1.02–1.30; P=0.04) (10). In contrast, another National Cancer Database study reported no significant difference in DFS between total thyroidectomy and lobectomy after propensity score matching in patients with pT1–2 pN0 PTC (HR =1.364; 95% CI: 0.228–8.159; P=0.73) (17). Furthermore, a systematic review and meta-analysis found no significant difference in pooled recurrence rates between total thyroidectomy with or without RAI therapy and hemithyroidectomy in T1–T2 N0 differentiated thyroid cancer [5.3% vs. 6.3%, respectively; odds ratio (OR) 1.21; 95% CI: 0.75–1.97; P=0.44] (18).

Regarding the subset of patients with 1–4 cm (T1b–T2) tumors, an analysis of 61,775 patients with 1–4 cm PTC found no difference in overall survival between those treated with lobectomy and total thyroidectomy, after adjusting for clinical and pathological factors (HR =0.96; 95% CI: 0.84–1.09; P=0.54) (12). Additionally, a separate analysis focusing on T2 PTC reported no difference in DFS between total thyroidectomy and lobectomy (P=0.87) (19). However, another study demonstrated that total thyroidectomy was associated with improved survival in patients with 2.0–3.9 cm conventional PTC (HR =1.53; 95% CI: 1.06–2.19; P=0.02) (20).

The present study adds to this body of evidence by demonstrating no significant differences in recurrence rates between lobectomy and total thyroidectomy in cN0 11–40 mm unilateral PTC. This trend was consistent across both the 11–20 and 21–40 mm PTC subgroups in both the baseline and PSM cohorts. However, recurrence was numerically higher after lobectomy than total thyroidectomy in the 21–40 mm subgroup before PSM. Given the small sample size and sparse events in this subgroup, the analysis was underpowered, and these findings should be interpreted cautiously rather than as evidence of equivalence.

In particular, the results of this study may be more reliable because the subjects with only unilateral PTC were homogeneous compared to previous studies that included bilateral tumors. Notably, postoperative RAI ablation was administered only in the total thyroidectomy cohort. Despite the application of RAI therapy, which serves as a more aggressive approach by targeting potential microscopic residual disease, no significant differences in DFS or recurrence rates were observed between the surgical groups. These findings suggest that lobectomy can be a viable and appropriate surgical option for managing low-risk T1b–T2 PTC, reinforcing that total thyroidectomy may not be necessary in these cases. Furthermore, the data align with the understanding that RAI treatment following total thyroidectomy does not substantially influence recurrence or survival outcomes in most low- to intermediate-risk PTC patients (21).

Follicular variant PTC generally exhibits a more indolent clinical course and lower rates of lymph node metastasis and recurrence than classic PTC (22). In our cohort, all nine cases of recurrence occurred in the classic PTC, with no recurrences observed in follicular variant PTC. It might suggest that lobectomy can be a primary surgical extent for follicular variant PTC measuring 11–40 mm.

Total thyroidectomy is generally associated with a higher incidence of complications compared to lobectomy. In the baseline and PSM cohorts, we observed a significantly higher incidence of hypoparathyroidism in the total thyroidectomy group relative to the lobectomy group, while no significant differences in other complications were identified between the two groups. These results remained consistent within both the 11–20 and 21–40 mm subgroups. Other reports suggested that calcium-related morbidity may increase as the extent of central-compartment manipulation expands (23,24). However, our study conducted PSM analysis, including CND, to eliminate potential CND confounding, so CND will not affect the hypoparathyroidism rate. The higher rate of seroma in the lobectomy group within the 21–40 mm subgroup is likely attributable to the small sample size.

Previous studies have indicated that minimal ETE has a relatively limited impact on DFS rates and plays a minor role in influencing key disease management decisions (25-29). Nevertheless, some studies have reported an association between minimal ETE and an increased rate of lymph node metastasis (30). Our findings similarly suggest that minimal ETE does not significantly affect recurrence or DFS outcomes. The eighth edition of the AJCC staging system (31) excluded minimal ETE as a staging criterion, emphasizing gross ETE as the primary focus. Under this system, gross ETE and strap muscle invasion are the only factors considered prognostic.

Previously, strap muscle invasion was classified as minimal ETE, but it is now recognized as a separate entity (T3 tumor in AJCC 8th edition) (31). Although some studies, including those with cohorts of 2,084 and 3,174 patients with differentiated thyroid cancer, reported that strap muscle invasion did not result in worse DFS compared to minimal ETE over long-term follow-up (32,33), the majority of evidence suggests that strap muscle invasion is associated with a poorer prognosis compared to minimal ETE. A study analyzing 4,045 patients with PTC indicated that strap muscle invasion was associated with significantly higher recurrence rates compared to minimal ETE (25.9% vs. 21.3%; P=0.03) (34). An additional study demonstrated that strap muscle invasion increased the risk of disease-specific mortality (35). Our current study also supports the finding that strap muscle invasion is a significant predictor of recurrence. In this context, several guidelines generally favor a total thyroidectomy-based approach when gross ETE is present: the 2015 ATA guidelines recommend near-total/total thyroidectomy when gross ETE is present (3). And the 2014 BTA guidelines recommend total thyroidectomy for tumors >4 cm, or for tumors of any size when associated with additional risk factors, including extra-thyroidal spread (15). Therefore, in patients with gross strap muscle invasion, a total thyroidectomy-based approach may be considered a guideline-concordant strategy. Nevertheless, our study is limited by the small number of patients with strap muscle invasion who underwent lobectomy, complicating efforts to draw meaningful comparisons between total thyroidectomy and lobectomy in this subgroup. Further research is warranted to determine the optimal extent of surgical intervention for patients with strap muscle invasion.

This study has several limitations. As a retrospective analysis, it is subject to inherent biases that may impact the generalizability of our findings, even though we performed PSM to mitigate baseline imbalances. Moreover, the sample size within the 21–40 mm subgroup and among patients with strap muscle invasion, particularly in the lobectomy cohort, was small, potentially limiting the statistical power and robustness of the subgroup analyses. In addition, recurrence events were sparse, leading to imprecise Cox regression estimates with wide CIs and limiting the stability of multivariable modeling, particularly after PSM; therefore, regression-based findings should be interpreted as exploratory and hypothesis-generating. Further investigations with larger cohorts and extended follow-up are warranted to validate these findings.

Conclusions

In patients with unilateral cN0 PTC measuring 11–40 mm (especially in the 11–20 mm group), the extent of thyroidectomy did not significantly influence recurrence or survival rates, regardless of tumor size and the presence of minimal ETE. Lobectomy appears to be an appropriate initial operation, providing disease control comparable to total thyroidectomy while reducing procedure-related morbidity. However, strap muscle invasion was identified as a factor associated with an increased risk of recurrence. Additional research is needed to delineate the optimal management strategies, including the extent of thyroidectomy.

Acknowledgments

The authors thank Prof. Soo Rack Ryu from Biostatistical Consulting and Research Lab, Medical Research Collaborating Center, Hanyang University, for her great contribution to the statistical analysis.

Footnote

Reporting Checklist: The authors have completed the TREND reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-1-561/rc

Data Sharing Statement: Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-1-561/dss

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-1-561/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-1-561/coif). K.T. serves as an unpaid editorial board member of Gland Surgery from April 2024 to March 2026. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Institutional Review Board (IRB) of Hanyang University Hospital (IRB No. 2023-11-023) and individual consent for this retrospective analysis was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Aschebrook-Kilfoy B, Ward MH, Sabra MM, et al. Thyroid cancer incidence patterns in the United States by histologic type, 1992-2006. Thyroid 2011;21:125-34. [Crossref] [PubMed]
2. Pontius LN, Oyekunle TO, Thomas SM, et al. Projecting Survival in Papillary Thyroid Cancer: A Comparison of the Seventh and Eighth Editions of the American Joint Commission on Cancer/Union for International Cancer Control Staging Systems in Two Contemporary National Patient Cohorts. Thyroid 2017;27:1408-16.
3. Haugen BR, Alexander EK, Bible KC, 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. [Crossref] [PubMed]
4. Pacini F, Fuhrer D, Elisei R, et al. 2022 ETA Consensus Statement: What are the indications for post-surgical radioiodine therapy in differentiated thyroid cancer? Eur Thyroid J 2022;11:e210046. [Crossref] [PubMed]
5. Jang A, Jin M, Kim CA, et al. Serum thyroglobulin testing after thyroid lobectomy in patients with 1-4 cm papillary thyroid carcinoma. Endocrine 2023;81:290-7. [Crossref] [PubMed]
6. Hsiao V, Light TJ, Adil AA, et al. Complication Rates of Total Thyroidectomy vs Hemithyroidectomy for Treatment of Papillary Thyroid Microcarcinoma: A Systematic Review and Meta-analysis. JAMA Otolaryngol Head Neck Surg 2022;148:531-9. [Crossref] [PubMed]
7. Gunn A, Oyekunle T, Stang M, et al. Recurrent Laryngeal Nerve Injury After Thyroid Surgery: An Analysis of 11,370 Patients. J Surg Res 2020;255:42-9. [Crossref] [PubMed]
8. Lee SJ, Song CM, Ji YB, et al. Risk factors for hypothyroidism and thyroid hormone replacement after hemithyroidectomy in papillary thyroid carcinoma. Langenbecks Arch Surg 2021;406:1223-31. [Crossref] [PubMed]
9. Cooper DS, Doherty GM, Haugen BR, et al. Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2006;16:109-42. [Crossref] [PubMed]
10. Bilimoria KY, Bentrem DJ, Ko CY, et al. Extent of surgery affects survival for papillary thyroid cancer. Ann Surg 2007;246:375-81; discussion 381-4. [Crossref] [PubMed]
11. American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009;19:1167-214. [Crossref] [PubMed]
12. Adam MA, Pura J, Gu L, et al. Extent of surgery for papillary thyroid cancer is not associated with survival: an analysis of 61,775 patients. Ann Surg 2014;260:601-5; discussion 605-7. [Crossref] [PubMed]
13. Mendelsohn AH, Elashoff DA, Abemayor E, et al. Surgery for papillary thyroid carcinoma: is lobectomy enough? Arch Otolaryngol Head Neck Surg 2010;136:1055-61. [Crossref] [PubMed]
14. Dottorini ME, Mansi L. British Thyroid Association guidelines. In: Perros P, editor. Guidelines for the Management of Thyroid Cancer. 2nd ed. London: Royal College of Physicians; 2007:1218-9.
15. Perros P, Boelaert K, Colley S, et al. Guidelines for the management of thyroid cancer. Clin Endocrinol (Oxf) 2014;81:1-122. [Crossref] [PubMed]
16. Adam MA, Goffredo P, Youngwirth L, et al. Same thyroid cancer, different national practice guidelines: When discordant American Thyroid Association and National Comprehensive Cancer Network surgery recommendations are associated with compromised patient outcome. Surgery 2016;159:41-50. [Crossref] [PubMed]
17. Di Filippo L, Giugliano G, Tagliabue M, et al. Total thyroidectomy versus lobectomy: surgical approach to T1-T2 papillary thyroid cancer. Acta Otorhinolaryngol Ital 2020;40:254-61. [Crossref] [PubMed]
18. Rodriguez Schaap PM, Botti M, Otten RHJ, et al. Hemithyroidectomy versus total thyroidectomy for well differentiated T1-2 N0 thyroid cancer: systematic review and meta-analysis. BJS Open 2020;4:987-94. [Crossref] [PubMed]
19. Kim H, Kim K, Bae JS, et al. Clinical assessment of T2 papillary thyroid carcinoma: a retrospective study conducted at a single tertiary institution. Sci Rep 2022;12:13548. [Crossref] [PubMed]
20. Rajjoub SR, Yan H, Calcatera NA, et al. Thyroid lobectomy is not sufficient for T2 papillary thyroid cancers. Surgery 2018;163:1134-43. [Crossref] [PubMed]
21. Lee HA, Song CM, Ji YB, et al. Efficacy of postoperative radioactive iodine therapy for patients with low and intermediate risk papillary thyroid carcinoma. Endocrine 2025;87:685-96. [Crossref] [PubMed]
22. Henke LE, Pfeifer JD, Baranski TJ, et al. Long-term outcomes of follicular variant vs classic papillary thyroid carcinoma. Endocr Connect 2018;7:1226-35. [Crossref] [PubMed]
23. Nasiri S, Meshkati Yazd SM, Mokhtari Ardekani A, et al. The effect of thymectomy during central neck dissection in papillary thyroid carcinoma: a case-controlled study. Updates Surg 2023;75:227-33. [Crossref] [PubMed]
24. Shahriarirad R, Meshkati Yazd SM, Zahedi R, et al. Evaluation of the role of prophylactic bilateral central neck lymph node dissection in patients with papillary thyroid carcinoma: a case controlled study. Updates Surg 2023;75:679-89. [Crossref] [PubMed]
25. Ito Y, Tomoda C, Uruno T, et al. Minimal extrathyroid extension does not affect the relapse-free survival of patients with papillary thyroid carcinoma measuring 4 cm or less over the age of 45 years. Surg Today 2006;36:12-8. [Crossref] [PubMed]
26. Hay ID, Johnson TR, Thompson GB, et al. 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. [Crossref] [PubMed]
27. Woo CG, Sung CO, Choi YM, et al. Clinicopathological Significance of Minimal Extrathyroid Extension in Solitary Papillary Thyroid Carcinomas. Ann Surg Oncol 2015;22:S728-33. [Crossref] [PubMed]
28. Jin BJ, Kim MK, Ji YB, et al. Characteristics and significance of minimal and maximal extrathyroidal extension in papillary thyroid carcinoma. Oral Oncol 2015;51:759-63. [Crossref] [PubMed]
29. Ji YB, Song CM, Kim D, et al. Efficacy of hemithyroidectomy in papillary thyroid carcinoma with minimal extrathyroidal extension. Eur Arch Otorhinolaryngol 2019;276:3435-42. [Crossref] [PubMed]
30. Song RY, Kim HS, Kang KH. Minimal extrathyroidal extension is associated with lymph node metastasis in single papillary thyroid microcarcinoma: a retrospective analysis of 814 patients. World J Surg Oncol 2022;20:170. [Crossref] [PubMed]
31. Edge S, Byrd DR, Compton CC, et al. AJCC Cancer Staging Manual. 8th ed. New York: Springer; 2017.
32. Amit M, Boonsripitayanon M, Goepfert RP, 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. [Crossref] [PubMed]
33. Park SY, Kim HI, Kim JH, et al. Prognostic significance of gross extrathyroidal extension invading only strap muscles in differentiated thyroid carcinoma. Br J Surg 2018;105:1155-62. [Crossref] [PubMed]
34. Li G, Li R, Song L, et al. Implications of Extrathyroidal Extension Invading Only the Strap Muscles in Papillary Thyroid Carcinomas. Thyroid 2020;30:57-64. [Crossref] [PubMed]
35. Harries V, McGill M, Yuan A, et al. Does macroscopic extrathyroidal extension to the strap muscles alone affect survival in papillary thyroid carcinoma? Surgery 2022;171:1341-7. [Crossref] [PubMed]