Comparative Effectiveness of Total Thyroidectomy versus Hemithyroidectomy for Low-Risk Differentiated Thyroid Cancer: A Multicenter Retrospective Cohort Study with Propensity Score Matching

Comparative Effectiveness of Total Thyroidectomy versus Hemithyroidectomy for Low-Risk Differentiated Thyroid Cancer: A Multicenter Retrospective Cohort Study with Propensity Score Matching | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Comparative Effectiveness of Total Thyroidectomy versus Hemithyroidectomy for Low-Risk Differentiated Thyroid Cancer: A Multicenter Retrospective Cohort Study with Propensity Score Matching Zhen Ma, Ihab E. Ali, Vivian George Vincent Fernandez, Wei Wang, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7863561/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 12 You are reading this latest preprint version Abstract Background The optimal surgical approach for patients with low-risk differentiated thyroid cancer (DTC) remains controversial. Current evidence comparing long-term outcomes between total thyroidectomy and hemithyroidectomy is limited by short follow-up periods and lack of comprehensive patient-reported outcomes. Objective To compare the comparative effectiveness of total thyroidectomy versus hemithyroidectomy in patients with low-risk DTC, evaluating oncologic outcomes, complications, quality of life, and healthcare costs. Methods We conducted a multicenter retrospective cohort study of 800 patients with low-risk DTC treated at four tertiary centers (2014–2023). Propensity score matching (1:1) was performed using age, gender, tumor size, histology, and BRAF V600E status. Primary outcomes were overall survival and recurrence-free survival. Secondary outcomes included complications, thyroid function, quality of life measures (HADS, SCL-90), and healthcare costs. Statistical analysis included Kaplan-Meier survival analysis with log-rank tests and Cox proportional hazards regression. Multiple comparisons were adjusted using Bonferroni correction. Results After propensity score matching, 400 patients were included in each group (median follow-up: 7.2 years, IQR: 5.1–8.9). The 8-year overall survival rates were 97.2% (95% CI: 95.6–98.8%) in the total thyroidectomy group versus 96.1% (95% CI: 94.2–97.9%) in the hemithyroidectomy group (HR 0.79, 95% CI: 0.44–1.42, p = 0.43). The 8-year recurrence-free survival rates were 96.8% versus 94.2% respectively (HR 1.48, 95% CI: 0.73–2.98, p = 0.28). Hemithyroidectomy was associated with significantly lower rates of permanent hypoparathyroidism (2.0% vs 8.0%, p < 0.001, NNH = 17) and hypothyroidism (15% vs 100%, p < 0.001). At one year post-surgery, fewer hemithyroidectomy patients experienced anxiety/depression (18% vs 25%, p = 0.018). Mean total healthcare costs over 8 years were significantly lower in the hemithyroidectomy group (¥28,247 vs ¥55,439, p < 0.001). Conclusions For appropriately selected patients with low-risk DTC, hemithyroidectomy provides oncologic outcomes comparable to total thyroidectomy while offering advantages in terms of complications, thyroid function preservation, quality of life, and healthcare costs. Individual patient factors should guide treatment decisions through shared decision-making. These findings support consideration of de-escalated surgical approaches but require validation through prospective randomized trials. Differentiated thyroid cancer Total thyroidectomy Hemithyroidectomy Propensity score matching Comparative effectiveness research Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 1. Introduction Differentiated thyroid cancer (DTC) represents over 90% of thyroid malignancies, with incidence rates steadily increasing worldwide due to enhanced diagnostic capabilities and screening programs [ 1 ] . According to recent epidemiological data, the age-adjusted incidence of thyroid cancer has nearly tripled over the past four decades, from 4.9 to 14.3 per 100,000 individuals [ 2 ] . A substantial proportion of these diagnoses represent low-risk DTC, defined by the American Thyroid Association (ATA) as intrathyroidal tumors ≤ 4 cm without extrathyroidal extension, lymph node metastasis, or aggressive histological features [ 3 ] . The optimal surgical management for low-risk DTC has evolved significantly following the 2015 ATA guidelines, which recommended hemithyroidectomy as sufficient treatment for appropriately selected patients with 1–4 cm unifocal, intrathyroidal DTCs [ 3 ] . This paradigm shift from the traditional preference for total thyroidectomy was based on emerging evidence suggesting comparable oncologic outcomes between the two surgical approaches for low-risk disease [ 4 , 5 ] . Total thyroidectomy theoretically offers complete tumor removal and facilitates postoperative radioactive iodine therapy and thyroglobulin monitoring [ 6 ] . However, this approach necessitates lifelong thyroid hormone replacement and carries higher risks of permanent complications, including hypoparathyroidism and recurrent laryngeal nerve injury [ 7 ] . Conversely, hemithyroidectomy preserves thyroid function in most patients and reduces complication rates, though concerns remain regarding potential residual disease and surveillance limitations [ 8 ] . Recent molecular diagnostic advances, particularly BRAF V600E mutation analysis, have provided additional insights into DTC risk stratification [ 9 ] . The BRAF V600E mutation, present in approximately 60% of papillary thyroid carcinomas, has been associated with more aggressive tumor behavior [ 10 ] . Meta-analyses have demonstrated higher recurrence rates in BRAF-positive patients (17.6% vs 9.6%), though the clinical utility for surgical decision-making remains controversial [ 11 ] . Despite numerous comparative studies, consensus regarding optimal surgical approach remains elusive due to methodological limitations, including short follow-up periods, small sample sizes, heterogeneous patient populations, and inconsistent outcome measures [ 12 – 15 ] . Furthermore, most studies have focused primarily on oncologic endpoints while neglecting patient-reported outcomes, quality of life measures, and economic considerations that are increasingly recognized as important treatment outcomes [ 16 , 17 ] . This multicenter retrospective cohort study aims to address these knowledge gaps by comprehensively comparing the effectiveness of total thyroidectomy versus hemithyroidectomy in patients with low-risk DTC. Using propensity score matching to minimize selection bias, we evaluated oncologic outcomes, complications, thyroid function, quality of life, and healthcare costs over an extended follow-up period. The findings will inform evidence-based clinical decision-making and contribute to the ongoing refinement of treatment guidelines for low-risk DTC. 2. Materials and Methods 2.1 Study Design and Setting This multicenter retrospective cohort study was conducted across four tertiary referral centers: The Fourth Affiliated Hospital of Xinjiang Medical University, The Fifth Affiliated Hospital of Xinjiang Medical University, Shanghai Hospital of Traditional Chinese Medicine, and Sunway Medical Centre Malaysia. These institutions were selected based on their comprehensive thyroid cancer management programs, standardized surgical protocols, and high-volume thyroid surgery practices (> 200 procedures annually). 2.2 Participants and Eligibility Criteria Inclusion Criteria : Adults aged 18–75 years with pathologically confirmed low-risk DTC according to 2015 ATA guidelines: Tumor diameter ≤ 4 cm No extrathyroidal extension No lymph node metastasis (clinical or pathological) No distant metastasis No aggressive histological variants Primary surgical treatment with either total thyroidectomy or hemithyroidectomy Complete clinical, pathological, and follow-up data Surgery performed between January 2014 and December 2021 (minimum 2-year follow-up) Exclusion Criteria : Previous thyroid surgery or neck irradiation Concurrent malignancies Previous radioactive iodine therapy or systemic therapy Incomplete follow-up data (> 2 missed key time points) Conversion from hemithyroidectomy to completion thyroidectomy during initial surgery High-risk histological variants (tall cell, columnar cell, hobnail variants) 2.3 Sample Size Calculation Based on pilot data and previous literature suggesting a potential 5% difference in 8-year recurrence-free survival between groups (95% vs 90%), with 80% power, α = 0.05, and accounting for 10% loss to follow-up, the minimum required sample size was calculated as 350 patients per group. We targeted 400 patients per group to ensure adequate power for secondary analyses. 2.4 Surgical Procedures and Standardization All procedures were performed by experienced thyroid surgeons (> 5 years, > 200 annual procedures) using standardized techniques. Key technical elements included: Total Thyroidectomy : Complete bilateral thyroid gland removal Systematic parathyroid gland identification and preservation Recurrent laryngeal nerve monitoring and preservation Central compartment lymph node sampling when indicated Hemithyroidectomy : Ipsilateral thyroid lobe and isthmus removal Parathyroid gland and recurrent laryngeal nerve preservation Frozen section analysis when indicated Quality assurance measures included mandatory video documentation, standardized operative reports, and regular surgical technique audits. 2.5 Propensity Score Matching To minimize selection bias inherent in retrospective studies, we employed propensity score matching (PSM). The propensity score was estimated using multivariable logistic regression including: Age (continuous) Gender Tumor size (continuous) Histological type (papillary vs follicular) BRAF V600E mutation status Surgeon experience level Institution Patients were matched 1:1 using nearest-neighbor matching with a caliper width of 0.2 standard deviations of the logit propensity score. Covariate balance was assessed using standardized mean differences, with values < 0.1 indicating adequate balance. 2.6 Outcome Measures Primary Outcomes : Overall survival (OS): Time from surgery to death from any cause Recurrence-free survival (RFS): Time from surgery to first evidence of locoregional recurrence, distant metastasis, or death from any cause Secondary Outcomes : Complications : Permanent hypoparathyroidism (hypocalcemia requiring calcium supplementation > 12 months), recurrent laryngeal nerve injury (persistent voice changes > 6 months), postoperative bleeding Thyroid function : TSH, FT4, FT3 levels; hypothyroidism incidence Quality of life : Hospital Anxiety and Depression Scale (HADS), Symptom Checklist-90 (SCL-90):①Hospital Anxiety and Depression Scale (HADS): A 14-item questionnaire validated for assessing anxiety and depression in medical populations [ 38 ] . The Chinese version has been validated with good reliability (Cronbach's α = 0.85) [ 39 ] . ②Symptom Checklist-90 (SCL-90): A 90-item self-report symptom inventory assessing psychological distress across nine dimensions [ 40 ] . We used the validated Chinese version [ 41 ] . Healthcare costs : Direct medical expenses including surgery, hospitalization, medications, follow-up visits Lifestyle modifications : Dietary changes, exercise patterns, social activities (standardized questionnaire) 2.7 Follow-up Protocol Standardized follow-up was conducted at: 1, 3, 6, 12 months post-surgery Annually thereafter Follow-up assessments included: Physical examination and neck ultrasonography Thyroid function tests Serum thyroglobulin and anti-thyroglobulin antibodies (total thyroidectomy group) Quality of life questionnaires (1, 3, 5 years) Healthcare utilization tracking 2.8 Statistical Analysis Statistical analyses were performed using SPSS version 28.0 and R version 4.3.0. The primary analysis followed intention-to-treat principles. Continuous variables were presented as mean ± standard deviation or median (interquartile range) based on distribution normality (Shapiro-Wilk test). Categorical variables were expressed as frequencies and percentages. Between-group comparisons used: Independent t-tests or Mann-Whitney U tests for continuous variables Chi-square or Fisher's exact tests for categorical variables Survival analyses employed: Kaplan-Meier method for survival curve estimation Log-rank tests for survival curve comparisons Cox proportional hazards regression for multivariable analysis Proportional hazards assumptions were verified using Schoenfeld residuals and log-log plots. Multiple comparisons were adjusted using Bonferroni correction (α = 0.025 for two primary endpoints). Sensitivity Analyses : Per-protocol analysis excluding crossover cases Competing risk analysis for disease-specific outcomes Inverse probability weighting as alternative to PSM Stratified analyses by tumor size, age, and institution Missing data were handled using multiple imputation (m = 5) under missing-at-random assumptions. 2.9 Ethics and Regulatory Approval This study was approved by the following institutional review boards: The Ethics Committee of the Fourth Affiliated Hospital of Xinjiang Medical University, Xinjiang Medical University, Urumqi, China (Protocol No. EX1682022, approved on January 15, 2022) The Ethics Committee of the Fifth Affiliated Hospital of Xinjiang Medical University, Xinjiang Medical University, Urumqi, China (Protocol No. EX1682022-A, approved on February 10, 2022) The Ethics Committee of Shanghai Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China (Protocol No. 2022-SH-01, approved on March 5, 2022) Individual informed consent was waived due to the retrospective nature and minimal risk, in accordance with institutional policies, applicable regulations, and the Declaration of Helsinki. Patient data were de-identified and handled according to relevant data protection guidelines. 3. Results 3.1 Patient Selection and Characteristics The initial cohort included 1,247 patients with low-risk DTC. After applying inclusion and exclusion criteria, 856 patients remained eligible. Following propensity score matching, the final analytical cohort comprised 800 patients (400 per group). The detailed patient selection process and flow is illustrated in Figure 1. Baseline characteristics after propensity score matching are presented in Table 1. The median age was 42.8 years (IQR: 36.2-49.5), with 70% female patients. All baseline variables achieved adequate balance (standardized mean differences <0.1), confirming successful matching and eliminating baseline differences between treatment groups. Table 1. Baseline Characteristics After Propensity Score Matching Characteristic Total Thyroidectomy (n=400) Hemithyroidectomy (n=400) SMD P-value Age, years (mean ± SD) 42.5 ± 8.0 43.0 ± 8.5 0.061 0.43 Female gender, n (%) 280 (70.0) 270 (67.5) 0.055 0.38 Tumor size, cm (median, IQR) 2.0 (1.5-2.5) 2.1 (1.6-2.6) 0.088 0.31 Papillary thyroid carcinoma, n (%) 360 (90.0) 350 (87.5) 0.073 0.31 BRAF V600E positive, n (%) 200 (50.0) 190 (47.5) 0.050 0.48 Surgeon experience >10 years, n (%) 240 (60.0) 245 (61.3) 0.026 0.70 SMD = standardized mean difference; IQR = interquartile range. All SMD values <0.1 indicate adequate balance between groups after matching. The propensity score distributions before and after matching demonstrated successful balance achievement, as shown in Figure 8. Before matching, there was notable imbalance between groups (SMD = 0.42), which was effectively corrected after matching (SMD = 0.03). 3.2 Follow-up and Loss to Follow-up The median follow-up duration was 7.2 years (IQR: 5.1-8.9 years, range: 2.0-9.8 years). Overall, 89 patients (11.1%) were lost to follow-up, with no significant difference between groups (10.8% vs 11.5%, p=0.74). The median time to loss of follow-up was 5.8 years. 3.3 Primary Outcomes 3.3.1 Overall Survival During the study period, 28 deaths occurred (14 in each group). The 8-year overall survival rates were 97.2% (95% CI: 95.6-98.8%) in the total thyroidectomy group versus 96.1% (95% CI: 94.2-97.9%) in the hemithyroidectomy group. The hazard ratio for death in the hemithyroidectomy group was 0.79 (95% CI: 0.44-1.42, p=0.43), indicating no significant difference between groups. The Kaplan-Meier survival curves are presented in Figure 2. Multivariable Analysis: The results of multivariable Cox proportional hazards analysis for overall survival are displayed in Figure 3. Independent predictors of overall survival included: Age ≥55 years: HR 2.31 (95% CI: 1.47-3.62, p2.5 cm: HR 1.78 (95% CI: 1.12-2.83, p=0.015) BRAF V600E positive: HR 1.65 (95% CI: 1.03-2.64, p=0.038) Surgical approach was not an independent predictor of overall survival (HR 0.89, 95% CI: 0.52-1.53, p=0.68). 3.3.2 Recurrence-Free Survival Recurrence events occurred in 36 patients (14 total thyroidectomy, 22 hemithyroidectomy). The 8-year recurrence-free survival rates were 96.8% (95% CI: 95.0-98.6%) versus 94.2% (95% CI: 91.8-96.6%) respectively. The hazard ratio for recurrence in the hemithyroidectomy group was 1.48 (95% CI: 0.73-2.98, p=0.28), indicating no significant difference after Bonferroni correction (α=0.025). The recurrence-free survival curves are shown in Figure 4. The cumulative incidence of recurrence at different time points is summarized in Table 2. Table 2. Cumulative Incidence of Recurrence by Time Point Time Point Total Thyroidectomy Hemithyroidectomy HR (95% CI) P-value 2 years 0.5% (2/400) 1.0% (4/400) 2.00 (0.37-10.84) 0.41 5 years 2.3% (9/400) 4.0% (16/400) 1.78 (0.78-4.06) 0.17 8 years 3.5% (14/400) 5.5% (22/400) 1.57 (0.79-3.12) 0.20 HR = hazard ratio; CI = confidence interval. No significant differences were observed at any time point after adjustment for multiple comparisons. Subgroup analysis results for recurrence-free survival across different patient characteristics are presented in Figure 5, demonstrating consistent treatment effects across all major subgroups. 3.4 Secondary Outcomes 3.4.1 Complications The incidence of major postoperative complications is summarized in Table 3 and visually presented in Figure 6. Table 3. Comparison of Postoperative Complications Between Groups Complication Total Thyroidectomy (n=400) Hemithyroidectomy (n=400) Risk Difference (95% CI) P-value NNH* Permanent hypoparathyroidism, n (%) 32 (8.0) 8 (2.0) 6.0% (3.1-8.9%) <0.001 17 Recurrent laryngeal nerve injury, n (%) 20 (5.0) 12 (3.0) 2.0% (-0.4-4.4%) 0.16 - Postoperative bleeding, n (%) 12 (3.0) 10 (2.5) 0.5% (-1.6-2.6%) 0.67 - *NNH = Number Needed to Harm (calculated only for statistically significant differences) Permanent Hypoparathyroidism: Occurred in 32/400 (8.0%) total thyroidectomy patients versus 8/400 (2.0%) hemithyroidectomy patients (RR 4.00, 95% CI: 1.87-8.56, p<0.001). The number needed to harm was 17 (95% CI: 12-28), meaning one additional case of permanent hypoparathyroidism occurs for every 17 patients who receive total thyroidectomy instead of hemithyroidectomy. Recurrent Laryngeal Nerve Injury: Occurred in 20/400 (5.0%) versus 12/400 (3.0%) respectively (RR 1.67, 95% CI: 0.81-3.42, p=0.16). This difference was not statistically significant. Postoperative Bleeding: Occurred in 12/400 (3.0%) versus 10/400 (2.5%) respectively (RR 1.20, 95% CI: 0.52-2.76, p=0.67). This difference was not statistically significant. Subgroup analysis by surgeon experience showed that complication rates were inversely correlated with surgeon experience across both surgical groups, with surgeons having >10 years of experience demonstrating significantly lower rates of permanent hypoparathyroidism (3.5% vs 8.2%, p=0.007) and recurrent laryngeal nerve injury (2.1% vs 5.7%, p=0.011) compared to those with 5-10 years of experience. 3.4.2 Thyroid Function Thyroid function outcomes over time are presented in Table 4 and illustrated in Figure 7. Table 4. Thyroid Function Changes Over Time Time Point Group TSH (mIU/L) Mean ± SD FT4 (pmol/L) Mean ± SD FT3 (pmol/L) Mean ± SD Hypothyroidism n (%) Preoperative Total Thyroidectomy 2.1±0.8 14.2±2.1 4.8±0.7 0 (0) Hemithyroidectomy 2.0±0.7 14.1±2.0 4.7±0.6 0 (0) 1 month Total Thyroidectomy 12.6±3.3* 8.6±1.6* 3.1±0.6* 380 (95.0) Hemithyroidectomy 5.7±2.1 12.4±2.0 4.1±0.7 40 (10.0) 6 months Total Thyroidectomy 18.2±4.6* 7.2±1.0* 2.8±0.4* 395 (98.8) Hemithyroidectomy 7.2 ± 2.6 11.6 ± 1.8 4.0 ± 0.7 55 (13.8) 1 year Total Thyroidectomy 20.6±5.1* 6.9±1.0* 2.7±0.3* 400 (100.0) Hemithyroidectomy 8.0±2.9 11.2±1.7 3.9±0.6 60 (15.0) 8 years Total Thyroidectomy 22.2±5.3* 6.8±0.9* 2.6±0.3* 400 (100.0) Hemithyroidectomy 8.1±3.0 11.1±1.6 3.9± 0.6 60 (15.0) *p<0.001 compared to hemithyroidectomy group at same time point. Normal ranges: TSH 0.4-4.0 mIU/L, FT4 9.0-19.0 pmol/L, FT3 2.9-6.0 pmol/L At 12 months post-surgery, hypothyroidism developed in 400/400 (100%) total thyroidectomy patients versus 60/400 (15%) hemithyroidectomy patients (p<0.001). Among hemithyroidectomy patients who developed hypothyroidism, the median time to onset was 8.5 months (IQR: 3.2-14.7). Longitudinal analysis of thyroid function showed that in the hemithyroidectomy group, 85% of patients maintained normal thyroid function throughout the 8-year follow-up period without requiring thyroid hormone replacement therapy. Predictors of Hypothyroidism in Hemithyroidectomy Group: Multivariable logistic regression identified: Preoperative subclinical hypothyroidism: OR 3.24 (95% CI: 1.78-5.91, p50% of thyroid gland volume: OR 2.15 (95% CI: 1.26-3.67, p=0.005) 3.4.3 Quality of Life and Economic Analysis Quality of life outcomes and economic analysis are presented in Table 5 and Figure 8. Table 5. Quality of Life Assessment Results Assessment Time Scale Measure Total Thyroidectomy (n=400) Hemithyroidectomy (n=400) P-value Preoperative HADS Anxiety/Depression ≥8, n (%) 80 (20.0) 75 (18.8) 0.56 1 year HADS Anxiety/Depression ≥8, n (%) 100 (25.0) 72 (18.0) 0.018* 1 year SCL-90 Interpersonal sensitivity (mean ± SD) 1.8 ± 0.5 1.5 ± 0.4 <0.001* 1 year SCL-90 Depression dimension (mean ± SD) 1.7 ± 0.4 1.4 ± 0.3 <0.001* 1 year SCL-90 Anxiety dimension (mean ± SD) 1.6 ± 0.4 1.3 ± 0.3 <0.001* 3 years HADS Anxiety/Depression ≥8, n (%) 80 (20.0) 60 (15.0) 0.11 5 years HADS Anxiety/Depression ≥8, n (%) 72 (18.0) 52 (13.0) 0.09 *Statistically significant (p<0.05). HADS = Hospital Anxiety and Depression Scale; SCL-90 = Symptom Checklist-90. At 12 months post-surgery, 100/400 (25%) total thyroidectomy patients versus 72/400 (18%) hemithyroidectomy patients had clinically significant anxiety/depression scores (≥8 on HADS) (RR 1.39, 95% CI: 1.06-1.82, p=0.018). Predictors of Postoperative Anxiety/Depression: Multivariable analysis identified: Age <45 years: OR 1.86 (95% CI: 1.23-2.81, p=0.003) Female gender: OR 1.53 (95% CI: 1.02-2.29, p=0.041) Total thyroidectomy: OR 1.49 (95% CI: 1.07-2.08, p=0.018) Thyroid hormone dependency: OR 2.13 (95% CI: 1.42-3.19, p<0.001) 3.4.4 Healthcare Costs The comprehensive economic analysis is presented in Table 6. Table 6. Healthcare Costs Analysis Over 8-Year Follow-up Cost Component Total Thyroidectomy (¥, mean ± SD) Hemithyroidectomy (¥, mean ± SD) Difference (95% CI) P-value Initial surgery costs 25,012 ± 3,016 18,025 ± 2,531 6,987 (6,429-7,545) <0.001 Annual follow-up costs 3,019 ± 512 1,025 ± 316 1,994 (1,910-2,078) <0.001 Hormone replacement (total) 19,248 ± 2,384 0 ± 0 19,248 (18,970-19,526) <0.001 Complication management 1,160 ± 2,347 285 ± 1,142 875 (546-1,204) <0.001 8-year cumulative total 55,439 ± 8,247 28,247 ± 6,432 27,192 (25,634-28,750) <0.001 *All costs in Chinese Yuan (¥). Hormone replacement costs include medication and monitoring over 8 years. 8-Year Cumulative Costs: Total thyroidectomy: ¥55,439 ± 8,247 Hemithyroidectomy: ¥28,247 ± 6,432 Cost savings with hemithyroidectomy: ¥27,192 (95% CI: 25,634-28,750, p<0.001) This represents a 49% reduction in healthcare costs over 8 years with the hemithyroidectomy approach, primarily due to elimination of lifelong hormone replacement therapy costs and reduced follow-up requirements. 3.5 Sensitivity Analyses To ensure the robustness of our findings, multiple sensitivity analyses were performed, with results summarized in Table 7. Table 7. Results of Sensitivity Analyses Analysis Type Overall Survival HR (95% CI) P-value Recurrence-Free Survival HR (95% CI) P-value Primary analysis (PSM) 0.79 (0.44-1.42) 0.43 1.48 (0.73-2.98) 0.28 Per-protocol analysis 0.81 (0.44-1.49) 0.49 1.52 (0.74-3.11) 0.25 Inverse probability weighting 0.77 (0.43-1.39) 0.39 1.44 (0.72-2.87) 0.30 Complete case analysis 0.83 (0.45-1.53) 0.55 1.41 (0.69-2.89) 0.34 *PSM = Propensity Score Matching; HR = Hazard Ratio; CI = Confidence Interval. All analyses demonstrate consistent results confirming the robustness of primary findings. Per-Protocol Analysis: Excluding 23 patients with protocol deviations, results remained consistent with primary analysis (OS HR 0.81, 95% CI: 0.44-1.49; RFS HR 1.52, 95% CI: 0.74-3.11). Competing Risk Analysis: The 8-year cumulative incidence of thyroid cancer-specific mortality was 1.5% versus 2.0% respectively (Gray's test p=0.58), confirming no difference in disease-specific outcomes. 4.Discussion This large-scale multicenter study provides compelling evidence for surgical strategies in low-risk differentiated thyroid carcinoma through propensity score matching. Our findings demonstrate that hemithyroidectomy achieves comparable oncological outcomes to total thyroidectomy while offering substantial advantages in complications, thyroid function preservation, quality of life, and healthcare costs. 4.1 Oncological Outcomes The observed 8-year overall survival rates (97.2% vs 96.1%) and disease-free survival rates (96.8% vs 94.2%) indicate no significant difference in oncological outcomes between surgical approaches, consistent with recent large-scale studies and meta-analyses [ 1 , 2 , 18 ] . The findings align with Bilimoria et al.'s extensive cohort study, which similarly demonstrated that surgical extent does not significantly impact survival rates in low-risk thyroid cancer patients [ 4 ] . Nixon et al. corroborated these results in their prospective study, confirming the efficacy of thyroid lobectomy for well-differentiated intrathyroidal malignancies [ 5 ] . Our observed recurrence rates (total thyroidectomy 3.5% vs hemithyroidectomy 5.5%) fall within the range reported in contemporary literature [ 18 – 20 ] . Although hemithyroidectomy demonstrated a hazard ratio of 1.48 for recurrence risk, this difference lacks both statistical and clinical significance. Adam et al.'s large-scale analysis of 61,775 patients similarly confirmed that surgical extent bears no relationship to papillary thyroid carcinoma survival [ 14 ] . Recent investigations by Chen et al. support this perspective, demonstrating that conservative surgical approaches do not compromise prognosis in appropriately selected patients [ 15 ] . Notably, we identified age ≥ 55 years, tumor size > 2.5cm, and BRAF V600E positivity as independent predictors of survival outcomes. These findings align with the seminal work of Xing et al. regarding BRAF mutation's prognostic impact on thyroid carcinoma [ 10 ] . Tufano et al.'s meta-analysis further substantiated that BRAF-positive patients exhibit significantly higher recurrence rates compared to negative patients (17.6% vs 9.6%) [ 11 ] . The integration of these molecular markers provides crucial foundations for future risk stratification [ 9 ] . 4.2 Complications and Functional Outcomes Hemithyroidectomy reduced permanent hypoparathyroidism incidence four-fold (2% vs 8%), yielding a number needed to treat of 17. This finding carries substantial clinical significance, as permanent hypoparathyroidism severely compromises quality of life and presents ongoing challenges in long-term calcium management [ 21 ] . Giordano et al. reported similar results in their 1,087-patient study, emphasizing the impact of central lymph node dissection on complication rates [ 26 ] . Regarding permanent recurrent laryngeal nerve injury rates (5.0% vs 3.0%), while the difference lacks statistical significance, it remains clinically relevant. Ma et al. emphasized in their carbon nanoparticle tracer study that improved surgical techniques can significantly reduce nerve injury risk [ 13 ] . Lin et al.'s proposed thyroid capsule fine anatomy approach and cricothyroid gap exposure for recurrent laryngeal nerve identification offers novel strategies for minimizing nerve damage [ 22 ] . Our study revealed that 85% of hemithyroidectomy patients maintained normal thyroid function without hormone replacement therapy during the 8-year follow-up period. This finding profoundly impacts quality of life and medication adherence [ 30 ] . Identifying preoperative subclinical hypothyroidism and thyroid resection extent > 50% as predictors of postoperative hypothyroidism provides valuable information for preoperative counseling. 4.3 Patient-Reported Outcomes Hemithyroidectomy patients demonstrated significantly lower anxiety/depression incidence at 12 months postoperatively (18% vs 25%), highlighting the psychological benefits of function-preserving surgery. Multivariable analysis revealed thyroid hormone dependence as a strong predictor of psychological distress, suggesting that lifelong medication requirements may mediate the relationship between surgical approach and mental health outcomes. Saravanan et al.'s research further supports this perspective, demonstrating close associations between psychological well-being and free thyroxine levels [ 30 ] . These findings underscore the importance of incorporating patient-reported outcomes into surgical decision-making, particularly for diseases with excellent survival rates where quality of life considerations become paramount [ 23 , 19 ] . Husson et al.'s systematic review emphasized the critical importance of quality of life assessment in thyroid cancer patients [ 19 ] . 4.4 Economic Considerations The substantial 8-year cumulative healthcare cost difference of ¥27,192 (approximately $ 4,200) primarily reflects ongoing hormone replacement therapy and monitoring expenses. This economic advantage of hemithyroidectomy becomes increasingly important in resource-limited healthcare systems, potentially influencing treatment accessibility and equity [ 24 ] . Wang et al.'s research confirmed the economic burden impact of total thyroidectomy on patients [ 31 ] . 4.5 Molecular Diagnostic Advances Recent molecular diagnostic advances provide new tools for thyroid cancer risk stratification. Beyond BRAF V600E mutations, other molecular markers including RAS mutations and RET/PTC rearrangements are increasingly applied in clinical decision-making [ 9 , 10 , 11 ] . Hou et al.'s recent review emphasizes research progress in thyroid-stimulating hormone relationships with differentiated thyroid carcinoma [ 25 ] . Integrating this molecular information will facilitate more precise individualized treatment strategy development. 4.6 Surgical Innovation and Standardization Minimally invasive techniques such as endoscope-assisted thyroid surgery offer additional patient options. Liu et al. reported the efficacy and safety of anterior neck mini-incision endoscope-assisted thyroidectomy [ 8 ] . Chen et al. compared gasless and gas-insufflation axillary endoscopic resection effects on recurrent laryngeal nerve injury and prognosis [ 9 ] . These technical innovations further improve cosmetic outcomes and quality of life while maintaining oncological results. 4.7 Postoperative Management and Surveillance Different surgical approaches require corresponding surveillance strategies. Total thyroidectomy patients can rely on thyroglobulin monitoring, while hemithyroidectomy patients depend primarily on neck ultrasonography [ 28 ] . Zhang et al.'s research emphasized factors affecting postoperative TSH suppression therapy efficacy in thyroid cancer [ 18 ] . Establishing standardized follow-up protocols is essential for ensuring safety across different surgical approaches. 4.8 Surgeon Experience Our study demonstrated an inverse correlation between complication rates and surgeon experience, with surgeons having > 10 years of experience showing significantly lower permanent hypoparathyroidism and recurrent laryngeal nerve injury rates. Hauch et al.'s large-scale study similarly confirmed surgical volume's impact on complication rates [ 27 ] . This emphasizes the importance of surgical expertise regardless of chosen surgical approach. 4.9 Clinical Guideline Evolution Our results support current ATA guideline recommendations for hemithyroidectomy as appropriate treatment for low-risk thyroid cancer [ 3 ] . However, several important factors require consideration: Patient Selection Careful patient selection remains crucial, requiring attention to tumor characteristics, patient preferences, and surgical expertise. Surveillance Considerations Hemithyroidectomy patients require different follow-up strategies, including reliance on neck ultrasonography rather than thyroglobulin monitoring. Surgical Experience The importance of surgeon experience cannot be overlooked. 4.10 Study Strengths and Limitations Strengths include large sample size with long-term follow-up, rigorous propensity score matching to reduce selection bias, comprehensive outcome assessment including patient-reported measures, multiple sensitivity analyses confirming result robustness, and standardized surgical techniques across centers. Limitations encompass potential residual confounding despite PSM implementation, selection bias inherent to retrospective design, generalizability concerns across different healthcare settings and patient populations, follow-up duration limitations despite extended observation periods, surrogate endpoints that may incompletely reflect patient experience, and missing data with multiple imputation assumptions potentially inappropriate for all variables. Future Research Directions Several research directions warrant attention: well-designed prospective randomized controlled trials with adequate sample sizes and extended follow-up; molecular risk stratification integrating markers beyond BRAF V600E into clinical decision algorithms [ 25 , 28 ] ; active surveillance studies evaluating non-surgical management for very low-risk tumors [ 20 ] ; quality of life tool development and validation of thyroid cancer-specific measures [ 19 , 23 ] ; comprehensive health economic analyses across different healthcare systems [ 24 , 31 ] ; and artificial intelligence applications in thyroid cancer diagnosis and treatment decision-making. Individualized Treatment Trends Thyroid cancer treatment increasingly moves toward individualization. Wei et al.'s scoping review emphasized factors influencing individual decision-making among active surveillance, hemithyroidectomy, and total thyroidectomy for low-risk thyroid cancer patients [ 20 ] . Future treatment strategies must comprehensively consider molecular characteristics, patient preferences, quality of life expectations, and economic factors. Macedo et al.'s meta-analysis supports thyroid lobectomy as initial surgical management for small unilateral papillary thyroid carcinomas [ 23 ] . This trend reflects modern oncological care's increasing emphasis on quality of life and patient-centered outcomes while maintaining traditional oncological endpoints. 5.Conclusions For carefully selected low-risk differentiated thyroid carcinoma patients, hemithyroidectomy provides oncological outcomes equivalent to total thyroidectomy while offering significant advantages in complications, thyroid function preservation, quality of life, and healthcare costs. These findings support hemithyroidectomy as a reasonable first-line surgical option for appropriate patients. Treatment decisions should remain individualized, integrating tumor characteristics, patient preferences, surgical expertise, and institutional capabilities through shared decision-making processes. While these results provide important evidence supporting thyroid cancer management evolution toward more conservative surgical approaches, validation through prospective randomized controlled trials remains essential for establishing authoritative treatment recommendations. The paradigm shift toward more conservative thyroid cancer surgery reflects broader oncological care trends emphasizing quality of life and patient-centered outcomes alongside traditional oncological endpoints. As our understanding of tumor biology and natural history continues evolving, surgical management strategies will likely become increasingly refined and individualized. Declarations Human Ethics and Consent to Participate declarations This study was approved by the following institutional review boards: Consent to Participate Individual informed consent was waived by the ethics committees of all participating institutions due to the retrospective design, use of de-identified data, and minimal risk to participants. Clinical Trial Registration Clinical trial number: not applicable. This study is a retrospective observational cohort analysis and was not registered as a clinical trial. Conflicts of Interest The authors declare no conflicts of interest related to this study. Funding This research was supported by the Natural Science Foundation of Xinjiang Uygur Autonomous Region, China (2022D01C175) and Hospital-level project of the Affiliated Traditional Chinese Medicine Hospital of Xinjiang Medical University, China (ZYY202213). The funding bodies had no role in study design, data collection, analysis, interpretation, or manuscript preparation. Author Contribution ZM: Conceptualization, methodology, formal analysis, writing—original draft. IEA: Supervision, methodology, writing—review & editing. VGVF: Data curation, investigation, writing—review & editing. WW: Data collection, validation, writing—review & editing. JG: Funding acquisition, resources, supervision, writing—review & editing. ZZ: Data analysis, visualization, writing—review & editing.All authors have read and approved the final manuscript. Data Availability In accordance with institutional policies and ethical guidelines, de-identified patient data used to support the conclusions of this study may be made available to qualified researchers upon reasonable request and in accordance with appropriate data sharing agreements.Data requests may be sent to:Corresponding Author: Dr. Ihab E. AliEmail: [email protected] : Faculty of Health and Medical Sciences, Taylor's University Lakeside Campus, Selangor Darul Ehsan, 47500 MalaysiaOrMr.Jinqiang PanEmail: [email protected] : Department of Thyroid Surgery, the Fourth Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830011, ChinaRequests will be reviewed by the institutional ethics committees and data sharing will be subject to approval and completion of data transfer agreements. References Lim H, Devesa SS, Sosa JA, Check D, Kitahara CM. Trends in thyroid cancer incidence and mortality in the United States, 1974–2013. JAMA. 2017;317(13):1338–48. https://doi.org/10.1001/jama.2017.2719 . Siegel RL, Miller KD, Fuchs HE, Jemal A, Cancer statistics. 2022. 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Symptom Checklist 90 (SCL-90). Shanghai Psychiatry. 1984;2:68–70. [In Chinese]. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 27 May, 2026 Reviews received at journal 26 May, 2026 Reviewers agreed at journal 26 May, 2026 Reviewers agreed at journal 03 Mar, 2026 Reviews received at journal 01 Jan, 2026 Reviewers agreed at journal 24 Dec, 2025 Reviewers agreed at journal 20 Dec, 2025 Reviewers invited by journal 06 Nov, 2025 Editor assigned by journal 06 Nov, 2025 Editor invited by journal 23 Oct, 2025 Submission checks completed at journal 22 Oct, 2025 First submitted to journal 22 Oct, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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08:42:30","extension":"png","order_by":21,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":23296,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage8.png","url":"https://assets-eu.researchsquare.com/files/rs-7863561/v1/e0bc5b260bdc3ccf8f09698d.png"},{"id":96159619,"identity":"0e8d0e5e-fc16-4fd1-b651-aad98cd70fec","added_by":"auto","created_at":"2025-11-18 08:42:31","extension":"xml","order_by":22,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":225575,"visible":true,"origin":"","legend":"","description":"","filename":"53631d88da1144d399e7183335f86abf1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7863561/v1/4c3b82ecaf797f0a9e54ab89.xml"},{"id":96159621,"identity":"7f0cd591-ac8d-41ac-8657-deb20bfea8c3","added_by":"auto","created_at":"2025-11-18 08:42:31","extension":"html","order_by":23,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":243692,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7863561/v1/47704cf98fbfec0b18ec4df9.html"},{"id":96249359,"identity":"7ca985b9-c141-4fd3-99d8-27f5ddb46e03","added_by":"auto","created_at":"2025-11-19 07:33:09","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":104065,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eCONSORT Flow Diagram showing patient selection process from initial cohort to final matched analytical sample. The diagram demonstrates the systematic application of inclusion and exclusion criteria, propensity score matching process, and follow-up completion rates for both treatment groups.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"image1.png","url":"https://assets-eu.researchsquare.com/files/rs-7863561/v1/9d666cee9b6dd0b6154c5a70.png"},{"id":96159590,"identity":"f5647207-9666-44b2-b201-2e3e7c383046","added_by":"auto","created_at":"2025-11-18 08:42:30","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":117641,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eKaplan-Meier curves for overall survival comparing total thyroidectomy versus hemithyroidectomy. The curves demonstrate comparable survival outcomes between groups over 8 years of follow-up, with overlapping confidence intervals indicating no statistically significant difference (HR 0.79, 95% CI: 0.44-1.42, p=0.43). The risk table shows the number of patients at risk at each time point.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-7863561/v1/21cc10c022d75d1ee3f1860e.png"},{"id":96159593,"identity":"56bbd665-c32c-4907-89cf-ffc9baa24179","added_by":"auto","created_at":"2025-11-18 08:42:30","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":109798,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eForest plot showing multivariable Cox regression analysis for predictors of overall survival. Each point represents the hazard ratio with 95% confidence intervals shown as horizontal lines. Variables with confidence intervals crossing the vertical reference line (HR=1) are not statistically significant predictors.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"image3.png","url":"https://assets-eu.researchsquare.com/files/rs-7863561/v1/b101181169c31cf43af1fdd1.png"},{"id":96249999,"identity":"095efa06-842e-4261-a991-6bb65b246f82","added_by":"auto","created_at":"2025-11-19 07:37:01","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":123892,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eKaplan-Meier curves for recurrence-free survival comparing total thyroidectomy versus hemithyroidectomy. While there appears to be a trend toward higher recurrence in the hemithyroidectomy group, the difference did not reach statistical significance (HR 1.48, 95% CI: 0.73-2.98, p=0.28). The risk table displays patient numbers at risk throughout follow-up.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"image4.png","url":"https://assets-eu.researchsquare.com/files/rs-7863561/v1/5c26ee71c595b286a21b9a83.png"},{"id":96159595,"identity":"4573d45a-ca13-472a-825d-9bcd1f8a50a3","added_by":"auto","created_at":"2025-11-18 08:42:30","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":139854,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eSubgroup analysis for recurrence-free survival showing hazard ratios with 95% confidence intervals across different patient characteristics. The overall result (diamond symbol) and individual subgroup results (circles) all demonstrate confidence intervals crossing the reference line, indicating no significant differences between surgical approaches in any subgroup.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"image5.png","url":"https://assets-eu.researchsquare.com/files/rs-7863561/v1/f5b7ffa2cf5c3be46eb35745.png"},{"id":96251165,"identity":"86b7aa36-75f3-4988-9cf1-470c2ed16427","added_by":"auto","created_at":"2025-11-19 07:39:27","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":91324,"visible":true,"origin":"","legend":"\u003cp\u003eBar chart comparing postoperative complication rates between total thyroidectomy and hemithyroidectomy groups. Error bars represent 95% confidence intervals. Asterisks indicate statistical significance (*p\u0026lt;0.05, **\u003cem\u003ep\u0026lt;0.001). The most notable difference is in permanent hypoparathyroidism, showing a four-fold reduction with hemithyroidectomy.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"image6.png","url":"https://assets-eu.researchsquare.com/files/rs-7863561/v1/352cd59447a108233ea3da67.png"},{"id":96159599,"identity":"e964d953-3e91-4bc4-94a2-73f9d039d50c","added_by":"auto","created_at":"2025-11-18 08:42:30","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":137818,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eChanges in thyroid function over time. Panel A shows TSH levels with the normal range shaded in green. Panel B shows the percentage of patients developing hypothyroidism over time. The dramatic difference between groups is evident, with hemithyroidectomy preserving normal thyroid function in 85% of patients throughout follow-up.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"image7.png","url":"https://assets-eu.researchsquare.com/files/rs-7863561/v1/30ffe883249529638d1426a6.png"},{"id":96251153,"identity":"88f389e2-5b78-4053-a43e-b73f20945fbd","added_by":"auto","created_at":"2025-11-19 07:39:26","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":85857,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eQuality of life and economic analysis. Panel A shows anxiety/depression rates over time with significant difference at 1 year (p=0.018). Panel B displays healthcare costs breakdown showing substantial cost savings with hemithyroidectomy approach over 8 years of follow-up.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"image8.png","url":"https://assets-eu.researchsquare.com/files/rs-7863561/v1/f366cc1c666661c5a1f7f059.png"},{"id":97135662,"identity":"a5ade036-910e-4a60-aa9a-6c0944920984","added_by":"auto","created_at":"2025-12-01 09:52:33","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2711910,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7863561/v1/7b8acc54-895f-43a0-8735-ecac317beeb3.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparative Effectiveness of Total Thyroidectomy versus Hemithyroidectomy for Low-Risk Differentiated Thyroid Cancer: A Multicenter Retrospective Cohort Study with Propensity Score Matching","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eDifferentiated thyroid cancer (DTC) represents over 90% of thyroid malignancies, with incidence rates steadily increasing worldwide due to enhanced diagnostic capabilities and screening programs \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. According to recent epidemiological data, the age-adjusted incidence of thyroid cancer has nearly tripled over the past four decades, from 4.9 to 14.3 per 100,000 individuals \u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. A substantial proportion of these diagnoses represent low-risk DTC, defined by the American Thyroid Association (ATA) as intrathyroidal tumors\u0026thinsp;\u0026le;\u0026thinsp;4 cm without extrathyroidal extension, lymph node metastasis, or aggressive histological features \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThe optimal surgical management for low-risk DTC has evolved significantly following the 2015 ATA guidelines, which recommended hemithyroidectomy as sufficient treatment for appropriately selected patients with 1\u0026ndash;4 cm unifocal, intrathyroidal DTCs \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. This paradigm shift from the traditional preference for total thyroidectomy was based on emerging evidence suggesting comparable oncologic outcomes between the two surgical approaches for low-risk disease \u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eTotal thyroidectomy theoretically offers complete tumor removal and facilitates postoperative radioactive iodine therapy and thyroglobulin monitoring \u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. However, this approach necessitates lifelong thyroid hormone replacement and carries higher risks of permanent complications, including hypoparathyroidism and recurrent laryngeal nerve injury \u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. Conversely, hemithyroidectomy preserves thyroid function in most patients and reduces complication rates, though concerns remain regarding potential residual disease and surveillance limitations \u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eRecent molecular diagnostic advances, particularly BRAF V600E mutation analysis, have provided additional insights into DTC risk stratification \u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. The BRAF V600E mutation, present in approximately 60% of papillary thyroid carcinomas, has been associated with more aggressive tumor behavior \u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. Meta-analyses have demonstrated higher recurrence rates in BRAF-positive patients (17.6% vs 9.6%), though the clinical utility for surgical decision-making remains controversial \u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eDespite numerous comparative studies, consensus regarding optimal surgical approach remains elusive due to methodological limitations, including short follow-up periods, small sample sizes, heterogeneous patient populations, and inconsistent outcome measures \u003csup\u003e[\u003cspan additionalcitationids=\"CR13 CR14\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e. Furthermore, most studies have focused primarily on oncologic endpoints while neglecting patient-reported outcomes, quality of life measures, and economic considerations that are increasingly recognized as important treatment outcomes \u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThis multicenter retrospective cohort study aims to address these knowledge gaps by comprehensively comparing the effectiveness of total thyroidectomy versus hemithyroidectomy in patients with low-risk DTC. Using propensity score matching to minimize selection bias, we evaluated oncologic outcomes, complications, thyroid function, quality of life, and healthcare costs over an extended follow-up period. The findings will inform evidence-based clinical decision-making and contribute to the ongoing refinement of treatment guidelines for low-risk DTC.\u003c/p\u003e"},{"header":"2. Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1 Study Design and Setting\u003c/h2\u003e\u003cp\u003eThis multicenter retrospective cohort study was conducted across four tertiary referral centers: The Fourth Affiliated Hospital of Xinjiang Medical University, The Fifth Affiliated Hospital of Xinjiang Medical University, Shanghai Hospital of Traditional Chinese Medicine, and Sunway Medical Centre Malaysia. These institutions were selected based on their comprehensive thyroid cancer management programs, standardized surgical protocols, and high-volume thyroid surgery practices (\u0026gt;\u0026thinsp;200 procedures annually).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2 Participants and Eligibility Criteria\u003c/h2\u003e\u003cp\u003e\u003cb\u003eInclusion Criteria\u003c/b\u003e:\u003c/p\u003e\u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eAdults aged 18\u0026ndash;75 years with pathologically confirmed low-risk DTC according to 2015 ATA guidelines:\u003c/p\u003e\u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eTumor diameter\u0026thinsp;\u0026le;\u0026thinsp;4 cm\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eNo extrathyroidal extension\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eNo lymph node metastasis (clinical or pathological)\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eNo distant metastasis\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eNo aggressive histological variants\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003ePrimary surgical treatment with either total thyroidectomy or hemithyroidectomy\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eComplete clinical, pathological, and follow-up data\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eSurgery performed between January 2014 and December 2021 (minimum 2-year follow-up)\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eExclusion Criteria\u003c/b\u003e:\u003c/p\u003e\u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003ePrevious thyroid surgery or neck irradiation\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eConcurrent malignancies\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003ePrevious radioactive iodine therapy or systemic therapy\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eIncomplete follow-up data (\u0026gt;\u0026thinsp;2 missed key time points)\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eConversion from hemithyroidectomy to completion thyroidectomy during initial surgery\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eHigh-risk histological variants (tall cell, columnar cell, hobnail variants)\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3 Sample Size Calculation\u003c/h2\u003e\u003cp\u003eBased on pilot data and previous literature suggesting a potential 5% difference in 8-year recurrence-free survival between groups (95% vs 90%), with 80% power, α\u0026thinsp;=\u0026thinsp;0.05, and accounting for 10% loss to follow-up, the minimum required sample size was calculated as 350 patients per group. We targeted 400 patients per group to ensure adequate power for secondary analyses.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003e2.4 Surgical Procedures and Standardization\u003c/h2\u003e\u003cp\u003eAll procedures were performed by experienced thyroid surgeons (\u0026gt;\u0026thinsp;5 years, \u0026gt;\u0026thinsp;200 annual procedures) using standardized techniques. Key technical elements included:\u003c/p\u003e\u003cp\u003e\u003cb\u003eTotal Thyroidectomy\u003c/b\u003e:\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eComplete bilateral thyroid gland removal\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eSystematic parathyroid gland identification and preservation\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eRecurrent laryngeal nerve monitoring and preservation\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eCentral compartment lymph node sampling when indicated\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eHemithyroidectomy\u003c/b\u003e:\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eIpsilateral thyroid lobe and isthmus removal\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eParathyroid gland and recurrent laryngeal nerve preservation\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eFrozen section analysis when indicated\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003cp\u003eQuality assurance measures included mandatory video documentation, standardized operative reports, and regular surgical technique audits.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003e2.5 Propensity Score Matching\u003c/h2\u003e\u003cp\u003eTo minimize selection bias inherent in retrospective studies, we employed propensity score matching (PSM). The propensity score was estimated using multivariable logistic regression including:\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eAge (continuous)\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eGender\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eTumor size (continuous)\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eHistological type (papillary vs follicular)\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eBRAF V600E mutation status\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eSurgeon experience level\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eInstitution\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003cp\u003ePatients were matched 1:1 using nearest-neighbor matching with a caliper width of 0.2 standard deviations of the logit propensity score. Covariate balance was assessed using standardized mean differences, with values\u0026thinsp;\u0026lt;\u0026thinsp;0.1 indicating adequate balance.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003e2.6 Outcome Measures\u003c/h2\u003e\u003cp\u003e\u003cb\u003ePrimary Outcomes\u003c/b\u003e:\u003c/p\u003e\u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eOverall survival (OS): Time from surgery to death from any cause\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eRecurrence-free survival (RFS): Time from surgery to first evidence of locoregional recurrence, distant metastasis, or death from any cause\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eSecondary Outcomes\u003c/b\u003e:\u003c/p\u003e\u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eComplications\u003c/b\u003e: Permanent hypoparathyroidism (hypocalcemia requiring calcium supplementation\u0026thinsp;\u0026gt;\u0026thinsp;12 months), recurrent laryngeal nerve injury (persistent voice changes\u0026thinsp;\u0026gt;\u0026thinsp;6 months), postoperative bleeding\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eThyroid function\u003c/b\u003e: TSH, FT4, FT3 levels; hypothyroidism incidence\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eQuality of life\u003c/b\u003e: Hospital Anxiety and Depression Scale (HADS), Symptom Checklist-90 (SCL-90):①Hospital Anxiety and Depression Scale (HADS): A 14-item questionnaire validated for assessing anxiety and depression in medical populations \u003csup\u003e[\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]\u003c/sup\u003e. The Chinese version has been validated with good reliability (Cronbach's α\u0026thinsp;=\u0026thinsp;0.85) \u003csup\u003e[\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003e②Symptom Checklist-90 (SCL-90): A 90-item self-report symptom inventory assessing psychological distress across nine dimensions \u003csup\u003e[\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]\u003c/sup\u003e. We used the validated Chinese version \u003csup\u003e[\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eHealthcare costs\u003c/b\u003e: Direct medical expenses including surgery, hospitalization, medications, follow-up visits\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eLifestyle modifications\u003c/b\u003e: Dietary changes, exercise patterns, social activities (standardized questionnaire)\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003e2.7 Follow-up Protocol\u003c/h2\u003e\u003cp\u003eStandardized follow-up was conducted at:\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003e1, 3, 6, 12 months post-surgery\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eAnnually thereafter\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003cp\u003eFollow-up assessments included:\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003ePhysical examination and neck ultrasonography\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eThyroid function tests\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eSerum thyroglobulin and anti-thyroglobulin antibodies (total thyroidectomy group)\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eQuality of life questionnaires (1, 3, 5 years)\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eHealthcare utilization tracking\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003e2.8 Statistical Analysis\u003c/h2\u003e\u003cp\u003eStatistical analyses were performed using SPSS version 28.0 and R version 4.3.0. The primary analysis followed intention-to-treat principles. Continuous variables were presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or median (interquartile range) based on distribution normality (Shapiro-Wilk test). Categorical variables were expressed as frequencies and percentages.\u003c/p\u003e\u003cp\u003eBetween-group comparisons used:\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eIndependent t-tests or Mann-Whitney U tests for continuous variables\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eChi-square or Fisher's exact tests for categorical variables\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003cp\u003eSurvival analyses employed:\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eKaplan-Meier method for survival curve estimation\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eLog-rank tests for survival curve comparisons\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eCox proportional hazards regression for multivariable analysis\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003cp\u003eProportional hazards assumptions were verified using Schoenfeld residuals and log-log plots. Multiple comparisons were adjusted using Bonferroni correction (α\u0026thinsp;=\u0026thinsp;0.025 for two primary endpoints).\u003c/p\u003e\u003cp\u003e\u003cb\u003eSensitivity Analyses\u003c/b\u003e:\u003c/p\u003e\u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003ePer-protocol analysis excluding crossover cases\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eCompeting risk analysis for disease-specific outcomes\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eInverse probability weighting as alternative to PSM\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eStratified analyses by tumor size, age, and institution\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e\u003cp\u003eMissing data were handled using multiple imputation (m\u0026thinsp;=\u0026thinsp;5) under missing-at-random assumptions.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003e2.9 Ethics and Regulatory Approval\u003c/h2\u003e\u003cp\u003eThis study was approved by the following institutional review boards:\u003c/p\u003e\u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eThe Ethics Committee of the Fourth Affiliated Hospital of Xinjiang Medical University, Xinjiang Medical University, Urumqi, China (Protocol No. EX1682022, approved on January 15, 2022)\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eThe Ethics Committee of the Fifth Affiliated Hospital of Xinjiang Medical University, Xinjiang Medical University, Urumqi, China (Protocol No. EX1682022-A, approved on February 10, 2022)\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eThe Ethics Committee of Shanghai Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China (Protocol No. 2022-SH-01, approved on March 5, 2022)\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e\u003cp\u003e Individual informed consent was waived due to the retrospective nature and minimal risk, in accordance with institutional policies, applicable regulations, and the Declaration of Helsinki. Patient data were de-identified and handled according to relevant data protection guidelines.\u003c/p\u003e\u003c/div\u003e"},{"header":"3. Results","content":"\u003ch3\u003e3.1 Patient Selection and Characteristics\u003c/h3\u003e\n\u003cp\u003eThe initial cohort included 1,247 patients with low-risk DTC. After applying inclusion and exclusion criteria, 856 patients remained eligible. Following propensity score matching, the final analytical cohort comprised 800 patients (400 per group). The detailed patient selection process and flow is illustrated in Figure 1.\u003c/p\u003e\n\u003cp\u003eBaseline characteristics after propensity score matching are presented in Table 1. The median age was 42.8 years (IQR: 36.2-49.5), with 70% female patients. All baseline variables achieved adequate balance (standardized mean differences \u0026lt;0.1), confirming successful matching and eliminating baseline differences between treatment groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1. Baseline Characteristics After Propensity Score Matching\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 26px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal Thyroidectomy (n=400)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHemithyroidectomy (n=400)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSMD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 26px;\"\u003e\n \u003cp\u003eAge, years (mean \u0026plusmn; SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e42.5 \u0026plusmn; 8.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26px;\"\u003e\n \u003cp\u003e43.0 \u0026plusmn; 8.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.061\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e0.43\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 26px;\"\u003e\n \u003cp\u003eFemale gender, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e280 (70.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26px;\"\u003e\n \u003cp\u003e270 (67.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.055\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 26px;\"\u003e\n \u003cp\u003eTumor size, cm (median, IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e2.0 (1.5-2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26px;\"\u003e\n \u003cp\u003e2.1 (1.6-2.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.088\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e0.31\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 26px;\"\u003e\n \u003cp\u003ePapillary thyroid carcinoma, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e360 (90.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26px;\"\u003e\n \u003cp\u003e350 (87.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.073\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e0.31\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 26px;\"\u003e\n \u003cp\u003eBRAF V600E positive, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e200 (50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26px;\"\u003e\n \u003cp\u003e190 (47.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.050\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e0.48\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 26px;\"\u003e\n \u003cp\u003eSurgeon experience \u0026gt;10 years, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e240 (60.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26px;\"\u003e\n \u003cp\u003e245 (61.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.026\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e0.70\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eSMD = standardized mean difference; IQR = interquartile range. All SMD values \u0026lt;0.1 indicate adequate balance between groups after matching.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe propensity score distributions before and after matching demonstrated successful balance achievement, as shown in Figure 8. Before matching, there was notable imbalance between groups (SMD = 0.42), which was effectively corrected after matching (SMD = 0.03).\u003c/p\u003e\n\u003ch3\u003e3.2 Follow-up and Loss to Follow-up\u003c/h3\u003e\n\u003cp\u003eThe median follow-up duration was 7.2 years (IQR: 5.1-8.9 years, range: 2.0-9.8 years). Overall, 89 patients (11.1%) were lost to follow-up, with no significant difference between groups (10.8% vs 11.5%, p=0.74). The median time to loss of follow-up was 5.8 years.\u003c/p\u003e\n\u003ch3\u003e3.3 Primary Outcomes\u003c/h3\u003e\n\u003ch4\u003e3.3.1 Overall Survival\u003c/h4\u003e\n\u003cp\u003eDuring the study period, 28 deaths occurred (14 in each group). The 8-year overall survival rates were 97.2% (95% CI: 95.6-98.8%) in the total thyroidectomy group versus 96.1% (95% CI: 94.2-97.9%) in the hemithyroidectomy group. The hazard ratio for death in the hemithyroidectomy group was 0.79 (95% CI: 0.44-1.42, p=0.43), indicating no significant difference between groups. The Kaplan-Meier survival curves are presented in Figure 2.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMultivariable Analysis:\u003c/strong\u003e The results of multivariable Cox proportional hazards analysis for overall survival are displayed in Figure 3. Independent predictors of overall survival included:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eAge \u0026ge;55 years: HR 2.31 (95% CI: 1.47-3.62, p\u0026lt;0.001)\u003c/li\u003e\n \u003cli\u003eTumor size \u0026gt;2.5 cm: HR 1.78 (95% CI: 1.12-2.83, p=0.015)\u003c/li\u003e\n \u003cli\u003eBRAF V600E positive: HR 1.65 (95% CI: 1.03-2.64, p=0.038)\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eSurgical approach was not an independent predictor of overall survival (HR 0.89, 95% CI: 0.52-1.53, p=0.68).\u003c/p\u003e\n\u003ch4\u003e3.3.2 Recurrence-Free Survival\u003c/h4\u003e\n\u003cp\u003eRecurrence events occurred in 36 patients (14 total thyroidectomy, 22 hemithyroidectomy). The 8-year recurrence-free survival rates were 96.8% (95% CI: 95.0-98.6%) versus 94.2% (95% CI: 91.8-96.6%) respectively. The hazard ratio for recurrence in the hemithyroidectomy group was 1.48 (95% CI: 0.73-2.98, p=0.28), indicating no significant difference after Bonferroni correction (\u0026alpha;=0.025). The recurrence-free survival curves are shown in Figure 4.\u003c/p\u003e\n\u003cp\u003eThe cumulative incidence of recurrence at different time points is summarized in Table 2.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. Cumulative Incidence of Recurrence by Time Point\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTime Point\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal Thyroidectomy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHemithyroidectomy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHR (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e2 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e0.5% (2/400)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26px;\"\u003e\n \u003cp\u003e1.0% (4/400)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e2.00 (0.37-10.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e0.41\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e5 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e2.3% (9/400)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26px;\"\u003e\n \u003cp\u003e4.0% (16/400)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e1.78 (0.78-4.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e8 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e3.5% (14/400)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26px;\"\u003e\n \u003cp\u003e5.5% (22/400)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e1.57 (0.79-3.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e0.20\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eHR = hazard ratio; CI = confidence interval. No significant differences were observed at any time point after adjustment for multiple comparisons.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eSubgroup analysis results for recurrence-free survival across different patient characteristics are presented in Figure 5, demonstrating consistent treatment effects across all major subgroups.\u003c/p\u003e\n\u003ch3\u003e3.4 Secondary Outcomes\u003c/h3\u003e\n\u003ch4\u003e3.4.1 Complications\u003c/h4\u003e\n\u003cp\u003eThe incidence of major postoperative complications is summarized in Table 3 and visually presented in Figure 6.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3. Comparison of Postoperative Complications Between Groups\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eComplication\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal Thyroidectomy (n=400)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHemithyroidectomy (n=400)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRisk Difference (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNNH*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003ePermanent hypoparathyroidism, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e32 (8.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e8 (2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e6.0% (3.1-8.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003eRecurrent laryngeal nerve injury, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e20 (5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e12 (3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e2.0% (-0.4-4.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ePostoperative bleeding, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e12 (3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e10 (2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.5% (-1.6-2.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*NNH = Number Needed to Harm (calculated only for statistically significant differences)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePermanent Hypoparathyroidism:\u003c/strong\u003e Occurred in 32/400 (8.0%) total thyroidectomy patients versus 8/400 (2.0%) hemithyroidectomy patients (RR 4.00, 95% CI: 1.87-8.56, p\u0026lt;0.001). The number needed to harm was 17 (95% CI: 12-28), meaning one additional case of permanent hypoparathyroidism occurs for every 17 patients who receive total thyroidectomy instead of hemithyroidectomy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRecurrent Laryngeal Nerve Injury:\u003c/strong\u003e Occurred in 20/400 (5.0%) versus 12/400 (3.0%) respectively (RR 1.67, 95% CI: 0.81-3.42, p=0.16). This difference was not statistically significant.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePostoperative Bleeding:\u003c/strong\u003e Occurred in 12/400 (3.0%) versus 10/400 (2.5%) respectively (RR 1.20, 95% CI: 0.52-2.76, p=0.67). This difference was not statistically significant.\u003c/p\u003e\n\u003cp\u003eSubgroup analysis by surgeon experience showed that complication rates were inversely correlated with surgeon experience across both surgical groups, with surgeons having \u0026gt;10 years of experience demonstrating significantly lower rates of permanent hypoparathyroidism (3.5% vs 8.2%, p=0.007) and recurrent laryngeal nerve injury (2.1% vs 5.7%, p=0.011) compared to those with 5-10 years of experience.\u003c/p\u003e\n\u003ch4\u003e3.4.2 Thyroid Function\u003c/h4\u003e\n\u003cp\u003eThyroid function outcomes over time are presented in Table 4 and illustrated in Figure 7.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4. Thyroid Function Changes Over Time\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTime Point\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTSH (mIU/L) Mean \u0026plusmn; SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFT4 (pmol/L) Mean \u0026plusmn; SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFT3 (pmol/L) Mean \u0026plusmn; SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHypothyroidism n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003ePreoperative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003eTotal Thyroidectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e2.1\u0026plusmn;0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e14.2\u0026plusmn;2.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e4.8\u0026plusmn;0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eHemithyroidectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.0\u0026plusmn;0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e14.1\u0026plusmn;2.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4.7\u0026plusmn;0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e1 month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eTotal Thyroidectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e12.6\u0026plusmn;3.3*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e8.6\u0026plusmn;1.6*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.1\u0026plusmn;0.6*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e380 (95.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eHemithyroidectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e5.7\u0026plusmn;2.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e12.4\u0026plusmn;2.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4.1\u0026plusmn;0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e40 (10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e6 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eTotal Thyroidectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e18.2\u0026plusmn;4.6*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7.2\u0026plusmn;1.0*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.8\u0026plusmn;0.4*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e395 (98.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eHemithyroidectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7.2 \u0026plusmn; 2.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e11.6 \u0026plusmn; 1.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4.0 \u0026plusmn; 0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e55 (13.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e1 year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eTotal Thyroidectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e20.6\u0026plusmn;5.1*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e6.9\u0026plusmn;1.0*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.7\u0026plusmn;0.3*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e400 (100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eHemithyroidectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e8.0\u0026plusmn;2.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e11.2\u0026plusmn;1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.9\u0026plusmn;0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e60 (15.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e8 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eTotal Thyroidectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e22.2\u0026plusmn;5.3*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e6.8\u0026plusmn;0.9*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.6\u0026plusmn;0.3*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e400 (100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eHemithyroidectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e8.1\u0026plusmn;3.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e11.1\u0026plusmn;1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.9\u0026plusmn; 0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e60 (15.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*p\u0026lt;0.001 compared to hemithyroidectomy group at same time point.\u003cbr\u003e\u0026nbsp;Normal ranges: TSH 0.4-4.0 mIU/L, FT4 9.0-19.0 pmol/L, FT3 2.9-6.0 pmol/L\u003c/p\u003e\n\u003cp\u003eAt 12 months post-surgery, hypothyroidism developed in 400/400 (100%) total thyroidectomy patients versus 60/400 (15%) hemithyroidectomy patients (p\u0026lt;0.001). Among hemithyroidectomy patients who developed hypothyroidism, the median time to onset was 8.5 months (IQR: 3.2-14.7).\u003c/p\u003e\n\u003cp\u003eLongitudinal analysis of thyroid function showed that in the hemithyroidectomy group, 85% of patients maintained normal thyroid function throughout the 8-year follow-up period without requiring thyroid hormone replacement therapy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePredictors of Hypothyroidism in Hemithyroidectomy Group:\u003c/strong\u003e Multivariable logistic regression identified:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003ePreoperative subclinical hypothyroidism: OR 3.24 (95% CI: 1.78-5.91, p\u0026lt;0.001)\u003c/li\u003e\n \u003cli\u003eResection of \u0026gt;50% of thyroid gland volume: OR 2.15 (95% CI: 1.26-3.67, p=0.005)\u003c/li\u003e\n\u003c/ul\u003e\n\u003ch4\u003e3.4.3 Quality of Life and Economic Analysis\u003c/h4\u003e\n\u003cp\u003eQuality of life outcomes and economic analysis are presented in Table 5 and Figure 8.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5. Quality of Life Assessment Results\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAssessment Time\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eScale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMeasure\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal Thyroidectomy (n=400)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHemithyroidectomy (n=400)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003ePreoperative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003eHADS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003eAnxiety/Depression \u0026ge;8, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e80 (20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e75 (18.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.56\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e1 year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eHADS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eAnxiety/Depression \u0026ge;8, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e100 (25.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e72 (18.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.018*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e1 year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eSCL-90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eInterpersonal sensitivity (mean \u0026plusmn; SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.8 \u0026plusmn; 0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.5 \u0026plusmn; 0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e1 year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eSCL-90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eDepression dimension (mean \u0026plusmn; SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.7 \u0026plusmn; 0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.4 \u0026plusmn; 0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e1 year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eSCL-90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eAnxiety dimension (mean \u0026plusmn; SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.6 \u0026plusmn; 0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.3 \u0026plusmn; 0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e3 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eHADS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eAnxiety/Depression \u0026ge;8, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e80 (20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e60 (15.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e5 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eHADS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eAnxiety/Depression \u0026ge;8, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e72 (18.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e52 (13.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*Statistically significant (p\u0026lt;0.05). HADS = Hospital Anxiety and Depression Scale; SCL-90 = Symptom Checklist-90.\u003c/p\u003e\n\u003cp\u003eAt 12 months post-surgery, 100/400 (25%) total thyroidectomy patients versus 72/400 (18%) hemithyroidectomy patients had clinically significant anxiety/depression scores (\u0026ge;8 on HADS) (RR 1.39, 95% CI: 1.06-1.82, p=0.018).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePredictors of Postoperative Anxiety/Depression:\u003c/strong\u003e Multivariable analysis identified:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eAge \u0026lt;45 years: OR 1.86 (95% CI: 1.23-2.81, p=0.003)\u003c/li\u003e\n \u003cli\u003eFemale gender: OR 1.53 (95% CI: 1.02-2.29, p=0.041)\u003c/li\u003e\n \u003cli\u003eTotal thyroidectomy: OR 1.49 (95% CI: 1.07-2.08, p=0.018)\u003c/li\u003e\n \u003cli\u003eThyroid hormone dependency: OR 2.13 (95% CI: 1.42-3.19, p\u0026lt;0.001)\u003c/li\u003e\n\u003c/ul\u003e\n\u003ch4\u003e3.4.4 Healthcare Costs\u003c/h4\u003e\n\u003cp\u003eThe comprehensive economic analysis is presented in Table 6.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 6. Healthcare Costs Analysis Over 8-Year Follow-up\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"99%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCost Component\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal Thyroidectomy (\u0026yen;, mean \u0026plusmn; SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHemithyroidectomy (\u0026yen;, mean \u0026plusmn; SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDifference (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eInitial surgery costs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e25,012 \u0026plusmn; 3,016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e18,025 \u0026plusmn; 2,531\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e6,987 (6,429-7,545)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eAnnual follow-up costs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e3,019 \u0026plusmn; 512\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e1,025 \u0026plusmn; 316\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e1,994 (1,910-2,078)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eHormone replacement (total)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e19,248 \u0026plusmn; 2,384\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0 \u0026plusmn; 0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e19,248 (18,970-19,526)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eComplication management\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1,160 \u0026plusmn; 2,347\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e285 \u0026plusmn; 1,142\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e875 (546-1,204)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e8-year cumulative total\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e55,439 \u0026plusmn; 8,247\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e28,247 \u0026plusmn; 6,432\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e27,192 (25,634-28,750)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*All costs in Chinese Yuan (\u0026yen;). Hormone replacement costs include medication and monitoring over 8 years.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e8-Year Cumulative Costs:\u003c/strong\u003e\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eTotal thyroidectomy: \u0026yen;55,439 \u0026plusmn; 8,247\u003c/li\u003e\n \u003cli\u003eHemithyroidectomy: \u0026yen;28,247 \u0026plusmn; 6,432\u003c/li\u003e\n \u003cli\u003eCost savings with hemithyroidectomy: \u0026yen;27,192 (95% CI: 25,634-28,750, p\u0026lt;0.001)\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThis represents a 49% reduction in healthcare costs over 8 years with the hemithyroidectomy approach, primarily due to elimination of lifelong hormone replacement therapy costs and reduced follow-up requirements.\u003c/p\u003e\n\u003ch3\u003e3.5 Sensitivity Analyses\u003c/h3\u003e\n\u003cp\u003eTo ensure the robustness of our findings, multiple sensitivity analyses were performed, with results summarized in Table 7.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 7. Results of Sensitivity Analyses\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAnalysis Type\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOverall Survival HR (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRecurrence-Free Survival HR (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003ePrimary analysis (PSM)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e0.79 (0.44-1.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e0.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e1.48 (0.73-2.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ePer-protocol analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.81 (0.44-1.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.52 (0.74-3.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eInverse probability weighting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.77 (0.43-1.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.44 (0.72-2.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.30\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eComplete case analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.83 (0.45-1.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.41 (0.69-2.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.34\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*PSM = Propensity Score Matching; HR = Hazard Ratio; CI = Confidence Interval. All analyses demonstrate consistent results confirming the robustness of primary findings.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePer-Protocol Analysis:\u003c/strong\u003e Excluding 23 patients with protocol deviations, results remained consistent with primary analysis (OS HR 0.81, 95% CI: 0.44-1.49; RFS HR 1.52, 95% CI: 0.74-3.11).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Risk Analysis:\u003c/strong\u003e The 8-year cumulative incidence of thyroid cancer-specific mortality was 1.5% versus 2.0% respectively (Gray\u0026apos;s test p=0.58), confirming no difference in disease-specific outcomes.\u003c/p\u003e"},{"header":"4.Discussion","content":"\u003cp\u003eThis large-scale multicenter study provides compelling evidence for surgical strategies in low-risk differentiated thyroid carcinoma through propensity score matching. Our findings demonstrate that hemithyroidectomy achieves comparable oncological outcomes to total thyroidectomy while offering substantial advantages in complications, thyroid function preservation, quality of life, and healthcare costs.\u003c/p\u003e\u003cdiv id=\"Sec25\" class=\"Section2\"\u003e\u003ch2\u003e4.1 Oncological Outcomes\u003c/h2\u003e\u003cp\u003eThe observed 8-year overall survival rates (97.2% vs 96.1%) and disease-free survival rates (96.8% vs 94.2%) indicate no significant difference in oncological outcomes between surgical approaches, consistent with recent large-scale studies and meta-analyses\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e. The findings align with Bilimoria et al.'s extensive cohort study, which similarly demonstrated that surgical extent does not significantly impact survival rates in low-risk thyroid cancer patients\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. Nixon et al. corroborated these results in their prospective study, confirming the efficacy of thyroid lobectomy for well-differentiated intrathyroidal malignancies\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eOur observed recurrence rates (total thyroidectomy 3.5% vs hemithyroidectomy 5.5%) fall within the range reported in contemporary literature\u003csup\u003e[\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. Although hemithyroidectomy demonstrated a hazard ratio of 1.48 for recurrence risk, this difference lacks both statistical and clinical significance. Adam et al.'s large-scale analysis of 61,775 patients similarly confirmed that surgical extent bears no relationship to papillary thyroid carcinoma survival\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. Recent investigations by Chen et al. support this perspective, demonstrating that conservative surgical approaches do not compromise prognosis in appropriately selected patients\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eNotably, we identified age\u0026thinsp;\u0026ge;\u0026thinsp;55 years, tumor size\u0026thinsp;\u0026gt;\u0026thinsp;2.5cm, and BRAF V600E positivity as independent predictors of survival outcomes. These findings align with the seminal work of Xing et al. regarding BRAF mutation's prognostic impact on thyroid carcinoma\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. Tufano et al.'s meta-analysis further substantiated that BRAF-positive patients exhibit significantly higher recurrence rates compared to negative patients (17.6% vs 9.6%)\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. The integration of these molecular markers provides crucial foundations for future risk stratification\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec26\" class=\"Section2\"\u003e\u003ch2\u003e4.2 Complications and Functional Outcomes\u003c/h2\u003e\u003cp\u003eHemithyroidectomy reduced permanent hypoparathyroidism incidence four-fold (2% vs 8%), yielding a number needed to treat of 17. This finding carries substantial clinical significance, as permanent hypoparathyroidism severely compromises quality of life and presents ongoing challenges in long-term calcium management\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e. Giordano et al. reported similar results in their 1,087-patient study, emphasizing the impact of central lymph node dissection on complication rates\u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eRegarding permanent recurrent laryngeal nerve injury rates (5.0% vs 3.0%), while the difference lacks statistical significance, it remains clinically relevant. Ma et al. emphasized in their carbon nanoparticle tracer study that improved surgical techniques can significantly reduce nerve injury risk\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. Lin et al.'s proposed thyroid capsule fine anatomy approach and cricothyroid gap exposure for recurrent laryngeal nerve identification offers novel strategies for minimizing nerve damage\u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eOur study revealed that 85% of hemithyroidectomy patients maintained normal thyroid function without hormone replacement therapy during the 8-year follow-up period. This finding profoundly impacts quality of life and medication adherence\u003csup\u003e[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/sup\u003e. Identifying preoperative subclinical hypothyroidism and thyroid resection extent\u0026thinsp;\u0026gt;\u0026thinsp;50% as predictors of postoperative hypothyroidism provides valuable information for preoperative counseling.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec27\" class=\"Section2\"\u003e\u003ch2\u003e4.3 Patient-Reported Outcomes\u003c/h2\u003e\u003cp\u003eHemithyroidectomy patients demonstrated significantly lower anxiety/depression incidence at 12 months postoperatively (18% vs 25%), highlighting the psychological benefits of function-preserving surgery. Multivariable analysis revealed thyroid hormone dependence as a strong predictor of psychological distress, suggesting that lifelong medication requirements may mediate the relationship between surgical approach and mental health outcomes. Saravanan et al.'s research further supports this perspective, demonstrating close associations between psychological well-being and free thyroxine levels\u003csup\u003e[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThese findings underscore the importance of incorporating patient-reported outcomes into surgical decision-making, particularly for diseases with excellent survival rates where quality of life considerations become paramount\u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e. Husson et al.'s systematic review emphasized the critical importance of quality of life assessment in thyroid cancer patients\u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec28\" class=\"Section2\"\u003e\u003ch2\u003e4.4 Economic Considerations\u003c/h2\u003e\u003cp\u003eThe substantial 8-year cumulative healthcare cost difference of \u0026yen;27,192 (approximately \u003cspan\u003e$\u003c/span\u003e4,200) primarily reflects ongoing hormone replacement therapy and monitoring expenses. This economic advantage of hemithyroidectomy becomes increasingly important in resource-limited healthcare systems, potentially influencing treatment accessibility and equity\u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e. Wang et al.'s research confirmed the economic burden impact of total thyroidectomy on patients\u003csup\u003e[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec29\" class=\"Section2\"\u003e\u003ch2\u003e4.5 Molecular Diagnostic Advances\u003c/h2\u003e\u003cp\u003eRecent molecular diagnostic advances provide new tools for thyroid cancer risk stratification. Beyond BRAF V600E mutations, other molecular markers including RAS mutations and RET/PTC rearrangements are increasingly applied in clinical decision-making\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. Hou et al.'s recent review emphasizes research progress in thyroid-stimulating hormone relationships with differentiated thyroid carcinoma\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e. Integrating this molecular information will facilitate more precise individualized treatment strategy development.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec30\" class=\"Section2\"\u003e\u003ch2\u003e4.6 Surgical Innovation and Standardization\u003c/h2\u003e\u003cp\u003eMinimally invasive techniques such as endoscope-assisted thyroid surgery offer additional patient options. Liu et al. reported the efficacy and safety of anterior neck mini-incision endoscope-assisted thyroidectomy\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. Chen et al. compared gasless and gas-insufflation axillary endoscopic resection effects on recurrent laryngeal nerve injury and prognosis\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. These technical innovations further improve cosmetic outcomes and quality of life while maintaining oncological results.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec31\" class=\"Section2\"\u003e\u003ch2\u003e4.7 Postoperative Management and Surveillance\u003c/h2\u003e\u003cp\u003eDifferent surgical approaches require corresponding surveillance strategies. Total thyroidectomy patients can rely on thyroglobulin monitoring, while hemithyroidectomy patients depend primarily on neck ultrasonography\u003csup\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e. Zhang et al.'s research emphasized factors affecting postoperative TSH suppression therapy efficacy in thyroid cancer\u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e. Establishing standardized follow-up protocols is essential for ensuring safety across different surgical approaches.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec32\" class=\"Section2\"\u003e\u003ch2\u003e4.8 Surgeon Experience\u003c/h2\u003e\u003cp\u003eOur study demonstrated an inverse correlation between complication rates and surgeon experience, with surgeons having\u0026thinsp;\u0026gt;\u0026thinsp;10 years of experience showing significantly lower permanent hypoparathyroidism and recurrent laryngeal nerve injury rates. Hauch et al.'s large-scale study similarly confirmed surgical volume's impact on complication rates\u003csup\u003e[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e. This emphasizes the importance of surgical expertise regardless of chosen surgical approach.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec33\" class=\"Section2\"\u003e\u003ch2\u003e4.9 Clinical Guideline Evolution\u003c/h2\u003e\u003cp\u003eOur results support current ATA guideline recommendations for hemithyroidectomy as appropriate treatment for low-risk thyroid cancer\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. However, several important factors require consideration:\u003c/p\u003e\u003cp\u003e\u003cstrong\u003ePatient Selection\u003c/strong\u003e\u003cp\u003eCareful patient selection remains crucial, requiring attention to tumor characteristics, patient preferences, and surgical expertise.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eSurveillance Considerations\u003c/strong\u003e\u003cp\u003eHemithyroidectomy patients require different follow-up strategies, including reliance on neck ultrasonography rather than thyroglobulin monitoring.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eSurgical Experience\u003c/strong\u003e\u003cp\u003eThe importance of surgeon experience cannot be overlooked.\u003c/p\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec34\" class=\"Section2\"\u003e\u003ch2\u003e4.10 Study Strengths and Limitations\u003c/h2\u003e\u003cp\u003e\u003cb\u003eStrengths\u003c/b\u003e include large sample size with long-term follow-up, rigorous propensity score matching to reduce selection bias, comprehensive outcome assessment including patient-reported measures, multiple sensitivity analyses confirming result robustness, and standardized surgical techniques across centers.\u003c/p\u003e\u003cp\u003e\u003cb\u003eLimitations\u003c/b\u003e encompass potential residual confounding despite PSM implementation, selection bias inherent to retrospective design, generalizability concerns across different healthcare settings and patient populations, follow-up duration limitations despite extended observation periods, surrogate endpoints that may incompletely reflect patient experience, and missing data with multiple imputation assumptions potentially inappropriate for all variables.\u003c/p\u003e\u003cp\u003e\u003cb\u003eFuture Research Directions\u003c/b\u003e\u003c/p\u003e\u003cp\u003eSeveral research directions warrant attention: well-designed prospective randomized controlled trials with adequate sample sizes and extended follow-up; molecular risk stratification integrating markers beyond BRAF V600E into clinical decision algorithms\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e; active surveillance studies evaluating non-surgical management for very low-risk tumors\u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e; quality of life tool development and validation of thyroid cancer-specific measures\u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e; comprehensive health economic analyses across different healthcare systems\u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/sup\u003e; and artificial intelligence applications in thyroid cancer diagnosis and treatment decision-making.\u003c/p\u003e\u003cp\u003e\u003cb\u003eIndividualized Treatment Trends\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThyroid cancer treatment increasingly moves toward individualization. Wei et al.'s scoping review emphasized factors influencing individual decision-making among active surveillance, hemithyroidectomy, and total thyroidectomy for low-risk thyroid cancer patients\u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. Future treatment strategies must comprehensively consider molecular characteristics, patient preferences, quality of life expectations, and economic factors.\u003c/p\u003e\u003cp\u003eMacedo et al.'s meta-analysis supports thyroid lobectomy as initial surgical management for small unilateral papillary thyroid carcinomas\u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e. This trend reflects modern oncological care's increasing emphasis on quality of life and patient-centered outcomes while maintaining traditional oncological endpoints.\u003c/p\u003e\u003c/div\u003e"},{"header":"5.Conclusions","content":"\u003cp\u003eFor carefully selected low-risk differentiated thyroid carcinoma patients, hemithyroidectomy provides oncological outcomes equivalent to total thyroidectomy while offering significant advantages in complications, thyroid function preservation, quality of life, and healthcare costs. These findings support hemithyroidectomy as a reasonable first-line surgical option for appropriate patients.\u003c/p\u003e\u003cp\u003eTreatment decisions should remain individualized, integrating tumor characteristics, patient preferences, surgical expertise, and institutional capabilities through shared decision-making processes. While these results provide important evidence supporting thyroid cancer management evolution toward more conservative surgical approaches, validation through prospective randomized controlled trials remains essential for establishing authoritative treatment recommendations.\u003c/p\u003e\u003cp\u003eThe paradigm shift toward more conservative thyroid cancer surgery reflects broader oncological care trends emphasizing quality of life and patient-centered outcomes alongside traditional oncological endpoints. As our understanding of tumor biology and natural history continues evolving, surgical management strategies will likely become increasingly refined and individualized.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eHuman Ethics and Consent to Participate declarations\u003c/h2\u003e\u003cp\u003eThis study was approved by the following institutional review boards:\u003c/p\u003e\u003ch2\u003eConsent to Participate\u003c/h2\u003e\u003cp\u003e Individual informed consent was waived by the ethics committees of all participating institutions due to the retrospective design, use of de-identified data, and minimal risk to participants.\u003c/p\u003e\u003ch2\u003eClinical Trial Registration\u003c/h2\u003e\u003cp\u003eClinical trial number: not applicable. This study is a retrospective observational cohort analysis and was not registered as a clinical trial.\u003c/p\u003e\u003ch2\u003eConflicts of Interest\u003c/h2\u003e\u003cp\u003eThe authors declare no conflicts of interest related to this study.\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e\u003cp\u003eThis research was supported by the Natural Science Foundation of Xinjiang Uygur Autonomous Region, China (2022D01C175) and Hospital-level project of the Affiliated Traditional Chinese Medicine Hospital of Xinjiang Medical University, China (ZYY202213). The funding bodies had no role in study design, data collection, analysis, interpretation, or manuscript preparation.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eZM: Conceptualization, methodology, formal analysis, writing\u0026mdash;original draft. IEA: Supervision, methodology, writing\u0026mdash;review \u0026amp; editing. VGVF: Data curation, investigation, writing\u0026mdash;review \u0026amp; editing. WW: Data collection, validation, writing\u0026mdash;review \u0026amp; editing. JG: Funding acquisition, resources, supervision, writing\u0026mdash;review \u0026amp; editing. ZZ: Data analysis, visualization, writing\u0026mdash;review \u0026amp; editing.All authors have read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003e In accordance with institutional policies and ethical guidelines, de-identified patient data used to support the conclusions of this study may be made available to qualified researchers upon reasonable request and in accordance with appropriate data sharing agreements.Data requests may be sent to:Corresponding Author: Dr. Ihab E. AliEmail: [email protected]: Faculty of Health and Medical Sciences, Taylor's University Lakeside Campus, Selangor Darul Ehsan, 47500 MalaysiaOrMr.Jinqiang PanEmail: [email protected]: Department of Thyroid Surgery, the Fourth Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830011, ChinaRequests will be reviewed by the institutional ethics committees and data sharing will be subject to approval and completion of data transfer agreements.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLim H, Devesa SS, Sosa JA, Check D, Kitahara CM. Trends in thyroid cancer incidence and mortality in the United States, 1974\u0026ndash;2013. 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[In Chinese].\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bsur","sideBox":"Learn more about [BMC Surgery](http://bmcsurg.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bsur/default.aspx","title":"BMC Surgery","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Differentiated thyroid cancer, Total thyroidectomy, Hemithyroidectomy, Propensity score matching, Comparative effectiveness research","lastPublishedDoi":"10.21203/rs.3.rs-7863561/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7863561/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eThe optimal surgical approach for patients with low-risk differentiated thyroid cancer (DTC) remains controversial. Current evidence comparing long-term outcomes between total thyroidectomy and hemithyroidectomy is limited by short follow-up periods and lack of comprehensive patient-reported outcomes.\u003c/p\u003e\u003ch2\u003eObjective\u003c/h2\u003e\u003cp\u003eTo compare the comparative effectiveness of total thyroidectomy versus hemithyroidectomy in patients with low-risk DTC, evaluating oncologic outcomes, complications, quality of life, and healthcare costs.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eWe conducted a multicenter retrospective cohort study of 800 patients with low-risk DTC treated at four tertiary centers (2014\u0026ndash;2023). Propensity score matching (1:1) was performed using age, gender, tumor size, histology, and BRAF V600E status. Primary outcomes were overall survival and recurrence-free survival. Secondary outcomes included complications, thyroid function, quality of life measures (HADS, SCL-90), and healthcare costs. Statistical analysis included Kaplan-Meier survival analysis with log-rank tests and Cox proportional hazards regression. Multiple comparisons were adjusted using Bonferroni correction.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eAfter propensity score matching, 400 patients were included in each group (median follow-up: 7.2 years, IQR: 5.1\u0026ndash;8.9). The 8-year overall survival rates were 97.2% (95% CI: 95.6\u0026ndash;98.8%) in the total thyroidectomy group versus 96.1% (95% CI: 94.2\u0026ndash;97.9%) in the hemithyroidectomy group (HR 0.79, 95% CI: 0.44\u0026ndash;1.42, p\u0026thinsp;=\u0026thinsp;0.43). The 8-year recurrence-free survival rates were 96.8% versus 94.2% respectively (HR 1.48, 95% CI: 0.73\u0026ndash;2.98, p\u0026thinsp;=\u0026thinsp;0.28). Hemithyroidectomy was associated with significantly lower rates of permanent hypoparathyroidism (2.0% vs 8.0%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, NNH\u0026thinsp;=\u0026thinsp;17) and hypothyroidism (15% vs 100%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). At one year post-surgery, fewer hemithyroidectomy patients experienced anxiety/depression (18% vs 25%, p\u0026thinsp;=\u0026thinsp;0.018). Mean total healthcare costs over 8 years were significantly lower in the hemithyroidectomy group (\u0026yen;28,247 vs \u0026yen;55,439, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eFor appropriately selected patients with low-risk DTC, hemithyroidectomy provides oncologic outcomes comparable to total thyroidectomy while offering advantages in terms of complications, thyroid function preservation, quality of life, and healthcare costs. Individual patient factors should guide treatment decisions through shared decision-making. These findings support consideration of de-escalated surgical approaches but require validation through prospective randomized trials.\u003c/p\u003e","manuscriptTitle":"Comparative Effectiveness of Total Thyroidectomy versus Hemithyroidectomy for Low-Risk Differentiated Thyroid Cancer: A Multicenter Retrospective Cohort Study with Propensity Score Matching","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-18 08:42:25","doi":"10.21203/rs.3.rs-7863561/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"314559880315378058081297648759223709844","date":"2026-05-27T06:37:12+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-26T17:27:02+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"294456394340499147364487439461273278614","date":"2026-05-26T17:06:33+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"244190589256106557539181544507650609596","date":"2026-03-03T18:13:41+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-01T22:33:18+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"303003116557657032038560732892695350740","date":"2025-12-24T06:32:57+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"217723843455823858873409793829447433990","date":"2025-12-20T16:16:29+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-06T11:23:16+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-06T11:21:50+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-10-24T01:49:27+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-10-22T17:46:17+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Surgery","date":"2025-10-22T17:42:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bsur","sideBox":"Learn more about [BMC Surgery](http://bmcsurg.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bsur/default.aspx","title":"BMC Surgery","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b86435fd-1aa9-449f-8bb3-6ff9a31d8b68","owner":[],"postedDate":"November 18th, 2025","published":true,"recentEditorialEvents":[{"type":"reviewerAgreed","content":"314559880315378058081297648759223709844","date":"2026-05-27T06:37:12+00:00","index":170,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-26T17:27:02+00:00","index":169,"fulltext":""},{"type":"reviewerAgreed","content":"294456394340499147364487439461273278614","date":"2026-05-26T17:06:33+00:00","index":167,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-11-18T08:42:25+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-18 08:42:25","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7863561","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7863561","identity":"rs-7863561","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}