Papillary thyroid microcarcinoma: insights from a cohort of 257 thyroidectomized patients

Papillary thyroid microcarcinoma: insights from a cohort of 257 thyroidectomized patients | 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 Papillary thyroid microcarcinoma: insights from a cohort of 257 thyroidectomized patients Henrique Cabral Scherer, Paula Fernandes, Rafael Selbach Scheffel, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1880064/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose: Active surveillance (AS) has been gaining attention as an option for papillary thyroid microcarcinoma (PTMC) management in selected patients. However, some questions remain on PTMC behavior, particularly on tumor multicentricity and cervical metastases. Our aim is to gather insights on the natural history of PTMC on patients treated with thyroidectomy. Methods: Consecutive patients diagnosed with PTMC (tumor size ≤ 1.0 cm) had their clinical characteristics, interventions, and outcomes described. Patients were classified as incidental or nonincidental based on the diagnosis of PTMC after or before surgery, respectively. Results: A cohort of 257 patients was included for this study, 84.0% of which were women, and the mean age was of 48.3 ± 13.5 years. The mean tumor size was of 0.68 ± 0.26 cm, 30.4% were multifocal, 24.5% had cervical metastasis, and 0.4% distant metastasis. The nonincidental and incidental tumors differed in tumor size (0.72 ± 0.24 and 0.60 ± 0.28 cm, respectively, p=0.003) and in presence of cervical metastasis (31.3% and 11.9%, respectively, p<0.001). Male sex, nonincidental diagnosis, and younger age were independent predictors of cervical metastasis. Notably, each year less in age represented an increase of 3% in likelihood of nodal metastasis (p<0.001). After 5.5 years (P25-75 2.5-9.7) of follow-up, only 3.8% of patients had persistent structural disease (3.4% cervical). Predictors of persistent disease at multivariate analysis included cervical metastasis and multicentricity. Conclusion: Incidental and nonincidental PTMC patients displayed excellent outcomes. Cervical metastasis and multicentricity are frequent findings in PTMC and prognostic factors for persistent disease. Papillary thyroid carcinoma Papillary thyroid microcarcinoma Treatment Prognosis Figures Figure 1 Figure 2 Introduction Thyroid carcinomas are the most common malignancy of the endocrine system, being responsible for nearly 2% of all cancer cases. In the last decades, thyroid cancer incidences increased worldwide [1-5], up to 15-fold in countries that adopted screening programs [3], and with substantial variability between and within populations. Mortality rates, however, remained stable or even decreased in most countries [1-3, 6]. Papillary thyroid carcinoma (PTC), the histologic type that accounts for more than 85% of thyroid carcinomas, has been shown to be responsible for most of thyroid cancer incidence’s growth [1, 2]. Almost half of new PTC cases can be due to small tumors with 10 mm or smaller diameter, called microcarcinomas (PTMC) [1]. Possibly due to enhanced healthcare access and increased sensitivity of diagnostic imaging methods [7-9], this data raised concerns on the risk of overdiagnosing PTC [5, 10], especially in PTMC cases, in which the tumors present favorable prognosis [11]. Given the surgical risks and potential consequences associated with thyroidectomies – such as vocal cord paralysis (VCP), hypoparathyroidism (Hypo-PT), and need for levothyroxine substitution – current recommendations point to the increasing relevance of more conservative treatment options. In this context, thyroid lobectomy and active surveillance (AS) emerge as safe and effective options for selected cases, with excellent clinical outcomes in long-term follow-up [12,13]. Moreover, these new approaches brought relevant discussion of PTMC decision-making process and its impact in several issues, including quality of life and healthcare costs [14, 15]. Nevertheless, current PTMC treatment approaches are predominantly aggressive worldwide, regarding surgical decisions and radioiodine (RAI) use, despite new evidence and guidelines [16, 17]. The applicability, patient selection, and decision-making between treatment options according to prognostic factors and potential benefits and risks, especially in real clinical care settings, are still a matter of study. In this study, we aim to gather insights on PTMC management and treatment perspectives in a cohort study of PTMC patients that underwent total thyroidectomy. We also explored if the clinical course and outcomes were different in PTMC classified as incidental and as nonincidental based on the diagnosis after and before surgery, respectively. Materials And Methods Patients and study design Patients from a cohort of differentiated thyroid cancer (DTC) were followed at the Thyroid Unit, Endocrine Division of Hospital de Clínicas de Porto Alegre (HCPA) – a tertiary care, university teaching hospital in southern Brazil. From 2000 to 2019, all consecutive patients with a histological diagnosis of PTC with a tumor size ≤ 10mm were included. Patients were classified with nonincidental diagnosis when the index nodule investigated had malignancy confirmed by fine needle aspiration biopsy (FNAB) or high suspicion for malignancy prior to surgical intervention decision, with confirmatory histopathological results. Incidental diagnosis was defined as diagnosis of PTC made in histopathological examination after thyroid surgery for other reasons. The study was approved by the ethics committee of the institution (CAAE 3095.4520.600005327/GPPG 2020-0182). Treatment protocol and follow-up All patients underwent thyroidectomy, some of them were referred to our Thyroid Unit after undergoing surgery in other institutions. Decisions regarding cervical lymph node dissection were made at the discretion of the surgical team at the Institution where the procedure was performed. The radioiodine (RAI) administration protocol used activities prescribed at the attending physician’s discretion. RAI was administered in a stimulated thyrotropin (TSH) condition of endogenous hypothyroidism (TSH >30 mUI/L), after withdrawing levothyroxine for at least 3-4 weeks [18]. A post-treatment whole body scan (post-treatment WBS) was performed seven to ten days after RAI administration [19]. In the first evaluation, the following data were recorded for each patient: demographics, tumor characteristics including histological features, extension and lymph node involvement, and treatment (e.g., surgery, RAI remnant ablation, and other interventions). Each patient was classified using the 8 th edition of the TNM/AJCC staging system (I, II, III, or IV) [20]. The “no evidence of lymph node metastasis” (N0) status was determined by clinical examination of the neck, preoperative and postoperative neck ultrasound (US) imaging, or by macroscopic examination during surgery and pathological examination of patients with lymph node resection. Distant metastasis (M1) was considered present when there was a lesion outside the cervical bed on imaging computed tomography (CT), or scintigraphy with histological confirmation, or post-treatment WBS uptake and/or elevated thyroglobulin (Tg). The risk of persistent/recurrent disease was assessed based on the proposed risk stratification system by the 2009 American Thyroid Association (ATA) guidelines, with patients classified into three risk groups: low, intermediate, and high [21]. The follow-up protocol called for an initial assessment at 3 to 6 months after the initial treatment, which included a physical examination of the neck and measurements of the serum Tg levels under TSH suppression (Tg-T4) and anti-thyroglobulin antibody (TgAb). In a second evaluation, 6 to 12 months after the initial treatment, physical examination of the neck and serum TSH, Tg-T4, and TgAb were reassessed. Some patients also had the serum level of Tg evaluated under stimulated TSH condition of endogenous hypothyroidism (TSH>30 mIU/L) (sTg) at the end of the first year of follow-up. Neck US was performed in this first year of follow-up. At this point, the patient was classified according to disease response to initial therapy (see below in the outcomes section). Patients classified as having an excellent response were scheduled for annual visits, during which a physical examination of the neck and measurements of TSH, Tg-T4, and TgAb were performed. Patients with indeterminate response or persistent disease were scheduled for the same examination at least twice a year. Additional imaging studies [e.g., x-ray, bone scintigraphy, CT] were performed, as needed, whenever the clinical or laboratory findings raised the suspicion of persistent or recurrent disease. Duration of follow-up was defined as the time between the first surgery and the last medical visit to the clinic. Outcomes Dynamic response to therapy status was defined based on clinical examination, Tg-T4 and/or sTg levels, neck US, post-RAI WBS (when available), and additional imaging exams when indicated. Patients were classified into four categories: excellent response, indeterminate response, biochemical incomplete response, or structural incomplete response [22, 23]. In patients submitted to RAI, excellent response was defined as negative imaging and Tg-T4 <0.2 ng/mL or sTg 1.0ng/mL or sTg >10.0 ng/mL or rising TgAb levels. Structural incomplete response was defined as structural or functional evidence of disease with any Tg or TgAb level. Indeterminate response was defined as non-specific findings on imaging studies or Tg-T4 between 0.2 to 1.0 ng/mL, sTg between 1.0 and 10.0 ng/mL, or positive TgAb with stable or declining levels [22]. In patients who underwent total thyroidectomy (TT) but did not receive RAI, excellent response was defined as negative imaging and Tg-T4 <0.2 ng/mL or sTg 5.0ng/mL, sTg >10.0 ng/mL, or increasing Tg levels over time or rising TgAb levels. Structural incomplete response was defined as structural or functional evidence of disease with any Tg or TgAb level. Indeterminate response was defined as non-specific findings on imaging studies or Tg-T4 between 0.2 to 5.0 ng/mL, sTg between 2.0 and 10.0 ng/mL, or positive TgAb with stable or declining levels [22]. For patients who underwent lobectomy, excellent response was defined as negative imaging and stable Tg-T4 level 30ng/mL, increasing Tg level values over time with similar TSH levels, or increasing TgAb levels. Structural incomplete response was defined as structural or functional evidence of disease with any Tg or TgAb level. Indeterminate response was defined as non-specific findings on imaging studies, positive TgAb levels stable, or declining in the absence of structural or functional disease [23]. For treatment response analysis, persistent disease was defined as either incomplete biochemical, cervical structural incomplete, or distant structural incomplete responses. Indeterminate response was combined with excellent response outcome, due to their similar prognosis after treatment, with 80-85% of these patients remaining either stable or improving to excellent response [24, 25]. Regarding surgical complications, permanent Hypo-PT was defined as hypocalcemia and low parathormone levels (PTH<20 pg/mL) for more than 1 year after surgery; this period was chosen, rather than the 6 months period of current guidelines [26], aiming for more conservative and accurate event rate report of long-term complications. Patients with no preoperative voice symptoms who presented with complaints of deficiency or quality alterations on voice for more than 1 year after surgery were considered to have persistent subjective voice disturbance (PSVD). Any surgical complication was defined as permanent Hypo-PT and/or PSVD. Laboratory analysis Serum Tg measurements were conducted using immunoradiometric assays: radioimmunoassay (COBRA II) from 2000 to 2002; electrochemiluminescence (ELECSYS 2010, Elecsys TG, Roche, Switzerland - analytical sensitivity of 1.0 ng/mL) from 2002 to 2005; electrochemiluminescence (MODULAR E-170, Elecsys TG, Roche, Switzerland- analytical sensitivity of 1.0 ng/mL) from 2005 to 2010; and chemiluminescence (Immulite XPI 2000, Siemens, Germany – analytical sensitivity of 0.2 ng/mL) from 2010 until the present. Serum TgAb levels were measured using the passive agglutination method from 2000 to 2010 (U-shaped microplates, Serodia-ATG, Japan – analytical sensitivity of 1/100); chemiluminescence from 2010 to 2018 (Architect ci 4100, Abbott, United States – analytical sensitivity 1.0 UI/mL); and chemiluminescence from 2019 until the present (DXI UNICEL 800, Beckman Coulter, United States – analytical sensitivity <0.9 UI/mL). TSH levels were measured by chemiluminescence assay from 2000 to 2006 (Immulite 2000 SIEMENS, Munich, Germany), electrochemiluminescence from 2006 to 2010 (Modular E ROCHE, Basel, Switzerland), chemiluminescence assay from 2010 to 2014 (Centaur XP SIEMENS, Munich, Germany), electrochemiluminescence from 2014 to 2019 (Cobas E602 ROCHE, Basel, Switzerland), and chemiluminescence immunoassay (Abbot, Chicago, USA) from 2019 until the present, with RV 0.35-4.94 mUI/L. Serum PTH was evaluated by chemiluminescent microparticle immunoassay method through the ARCHITECT ci 4100 equipment (Abbott Diagnostics, Abbott Park, IL, USA), with reference values (RV) of 15.0–68.3 pg/mL; intra-assay and inter-assay coefficients of variation were 6.1 and 6.4%, respectively. Total serum calcium was evaluated by the NM-BAPTA method and corrected by albumin levels (corrected calcium = 0.8 × [4.0−serum albumin] + serum calcium) with RV 8.6 to 10.0 mg/dL. Serum phosphorus was evaluated by the Molybdate UV and colorimetric (xylidyl blue) methods, with RV 2.5–4.5 mg/dL. The electrolyte tests were made using Cobas 8000 c702 equipment (Roche Diagnostics, Indianapolis, IN, USA). After each new assay had been implemented, the necessary procedures for standardization and validation were performed. These tests were all conducted in the central laboratory of HCPA. Statistical analysis The clinical and laboratory data are reported as the mean ± standard deviation (SD) values or as the median and percentiles 25 and 75 (P25-75) for continuous variables, and as absolute numbers and percentages for categorical variables. Statistical analyses were performed using Pearson chi-square and Fisher’s exact test for categorical variables, and Student’s t-test and Mann-Whitney U-test for continuous variables, as appropriate. For multivariate analysis models, Poisson regression was used, in which relative risk (RR) represented likelihood of associated events with a confidence interval (CI) of 95%. All tests were two-tailed, and all analyses were performed using the Statistical Package for Social Science Professional software version 20.0 (IBM Corp., Armonk, NY). A two-tailed P<0.05 was considered statistically significant. The e!Sankey software (iPoint-systems gmbh., Reutlingen, Germany) was used to build figures. Results Patients A total of 257 (23.5%) patients amongst the 1,091 patients of the institutional DTC cohort had PTC smaller or equal to 10 mm. Of these 257 PTMC patients, 84.0% were female, and the mean age of diagnosis was 48.3 ± 13.5 years (Table 1). The mean tumor size was 0.68 ± 0.26 cm, and 30.4% of them presented multicentric disease. 63 (24.5%) patients had nodal dissemination of the disease, and only 1 patient had distant metastasis (0.4%), which occurred in the lungs. Most patients, n=241 (93.8%), were classified as TNM Stage I, and 16 (6.2%) as TNM Stage II. Regarding 2009 ATA Risk Stratification System, 170 (66.1%) were classified as low risk, 86 (33.5%) as intermediate risk, and 1 (0.4%) as high risk. All patients underwent TT, with exception of 2 lobectomies. 156 (60.7%) patients received RAI therapy, with a mean RAI activity of 88.3 ± 34.5 mCi. N onincidental versus incidental diagnosis The pre-surgical clinical evaluation was available for 207 patients: 115 (55.6%) were classified as nonincidental diagnosis, and 92 (44.4%) as incidental (Table 2). Nonincidental diagnosis, when compared with incidental diagnosis, was associated with larger tumors (0.72 ± 0.24 and 0.60 ± 0.28 cm, respectively, P=0.003), more frequent cervical metastasis (36 (31.3%) and 11 (11.9%), respectively, P=0.001), and a larger proportion of TNM stage II classification (11 (9.6%) and 1 (1.1%), respectively, P=0.009). No difference in the proportion of RAI prescription was observed between incidental and nonincidental groups (49 (55.7%) and 66 (58.9%), respectively, P=0.685); The RAI activity dose was also similar between the groups (82.2 ± 32.5 and 91.8 ± 33.8 mCi, respectively, P=0.144). Clinical outcomes and lymph node metastasis predictors The dynamic response to therapy after initial treatment was defined in 224 patients (Table 1), with an excellent response observed in 130 (58.0%) patients, indeterminate response in 74 (33.0%), biochemical incomplete response in 10 (4.5%), cervical structural incomplete response in 9 (4.0%), and distant structural incomplete response in 1 (0.4%). The patient with M1, classified as ATA high-risk, was a 40-year-old male with a 0.4 cm (larger nodule) multicentric tumor, who presented lateral cervical lymph node and distant lung metastasis. After a median follow-up of 5.5 years (P25-P75 2.6-9.7), the dynamic response to therapy at last follow-up of the cohort was defined for 233 patients: excellent response was observed in 147 (63.1%) patients, indeterminate response in 66 (28.3%), biochemical incomplete response in 11 (4.7%), cervical structural incomplete response in 8 (3.4%), and distant structural incomplete response in only 1 (0.4%). Figure 1 depicts the patients’ dynamic response to therapy evolution between initial response to treatment and at last follow-up. During this period, 27 (12.0%) patients improved their response to therapy status, 185 (82.5%) remained in the same stratum, and 12 (5.3%) worsened response to therapy status. The characteristics and tumor features of the 20 patients with persistent disease – incomplete biochemical, cervical structural incomplete, and distant structural incomplete responses – are listed in the Supplementary Table 1. Predictors of persistent disease at univariate analysis for the 20 patients with this classification at last follow-up included male sex (P=0.041), lymph node metastasis (P<0.001), more advanced ATA risk stratification system classification (P<0.001), and persistent disease after initial treatment (P<0.001) (Table 3). No difference in RAI activity was observed between patients with excellent or indeterminate response versus persistent disease. No differences in treatment response were observed between the incidental and the nonincidental diagnosis groups. In multivariate analysis – regarding sex, age, tumor size, multicentricity, lymph node metastasis, and type of diagnosis – lymph node metastasis (P=0.004; RR=4.48, 95%CI 1.6-12.3) and multicentricity (P=0.039; RR=2.42, 95%CI 1.04-5.6) remained as predictors of persistent disease (Table 4). Nonincidental diagnosis was associated with a tendency of persistency of the disease (P=0.078; RR=2.19, 95%CI 0.91-5.26), as well as younger age (P=0.089; RR=1.05, 95%CI 0.99-1.11). Younger age at diagnosis (P<0.0001), male sex (P<0.001), and multicentricity (P=0.048) were associated with higher rates of lymph node metastasis (Table 5). Further analysis using the multivariate models identified male sex (P<0.001; RR=2.30, 95%CI 1.51-3.52), younger age (P<0.001; RR=1.03, 95%CI 1.01-1.04) and nonincidental diagnosis (P=0.010; RR=2.17, 95%CI 1.20-3.92) as predictors of lymph node metastasis (Table 4). Each reduction in 1 year in age was associated with an increased risk of 3% for nodal metastasis. Figure 2 depicts the distribution of lymph node metastasis in different age groups. Surgical complications Regarding surgical complications, a total of 20 (7.8%) patients developed permanent Hypo-PT, and 14 (5.4%) suffered from PSVD. Any long-term surgical complication, defined as Hypo-PT and/or PSVD, occurred in 31 (12.1%) patients, and 3 patients suffered from both permanent Hypo-PT and PSVD. Notably, there was a tendency to more long-term surgical complications in the nonincidental diagnosis than in the incidental diagnosis group (15 [13.5%] and 5 [5.6%], respectively, P=0.062). Lymph node resection data was available for 216 patients. Permanent Hypo-PT was more frequent in patients who underwent lymph node resection compared to those who didn’t (14 (10.8%) and 2 (2.3%), P=0.02), but no association of lymph node resection with PSVD (6 (4.8%) and 5 (5.9%), P=0.72) or any surgical complication (18 (14.3%) vs 8 (9.4%), P=0.291) was observed. Discussion We studied a cohort of patients with PTMC who underwent thyroidectomy. Among the 1,091 PTC patients of our cohort, we found a PTMC proportion similar to the literature report [27]. Moreover, we observed that 30.4% of them presented multicentric disease and 24.5% had lymph node metastasis at diagnosis. Another interesting finding is that most of the patients were disease-free after a median follow-up of 5.5 years. The lymph node is the main site of metastasis of PTC. In our PMTC cohort we observed in multivariate analysis that for nonincidental diagnosis, male sex and younger age were predictors of lymph node metastasis. This is consistent with previous reports that found male sex, multicentricity, and younger age to be associated with lymph node metastasis [28]. Younger age is usually associated with more advanced PTMC disease [29, 30]. In accordance with this observation, we found an association of younger age with nodal dissemination, but not with worse treatment response. Interestingly, in published active surveillance (AS) strategies, younger age is the most significant predictor of tumor growth and development of lymph node metastasis [30, 31]. All these data point to a pattern of more extensive and progressive disease in younger patients. Most PTMC patients were classified as excellent response after the initial treatment and at last follow-up. Disease response to therapy status remained stable over time for most patients, while some demonstrated status improvement and very few progressions of disease. These findings support the long-term excellent prognosis of PTMC tumors. Both ATA risk classification (P=0.006) and dynamic risk stratification at initial treatment (P<0.001) were predictors of excellent response in the last follow-up, reassuring these tools as useful methods for PTMC management. Multifocality and lymph node metastasis, were associated with persistent disease at last follow-up. Although associated with larger tumors and lymph node dissemination in our cohort, nonincidental diagnosis was not associated with worse response to treatment, a finding that may be due to underpower. Notably, a recent meta-analysis found significative higher risk of recurrence in nonincidental PTMC [32]. In our study, we observed 3.8% of structural persistent disease at last follow-up (3.4% cervical) in our cohort, and available reports of structural persistence/recurrence range from 1 to 6% [27, 33, 34]. We also observed high rates of surgical complications, represented by permanent Hypo-PT and PSVD, totaling 12.1% of any adverse event in these patients. These surgical complications have been associated with increased treatment costs within the health system [14] and worse quality of life outcomes [15], especially for permanent Hypo-PT regarding the former (due to costs of exams, hospital outpatient and inpatient visits, and pharmacological treatment) and voice disturbance regarding the latter. Since these are key factors in treatment decision-making [35], we further encourage physicians to consider local surgical complication rates to perform patient-shared and patient-centered decisions in PTMC diagnosis, aiming for better quality of life outcomes and healthcare costs. In this scenario of excellent clinical PTMC outcomes, AS emerges as a safe and effective option for selected cases [12,13]. Cohorts of PTMC under AS have shown that a minority of these patients evolve to surgery due to disease progression, and in these cases, despite postponement of the surgical treatment, oncological outcomes were excellent [30, 36]. In addition, AS can effectively reduce adverse events related to the management of these generally indolent tumors [37]. This is especially significant in a healthcare scenario containing a large proportion of PTMC cases and a significant risk associated with surgical treatment, such as ours. Patient selection to this approach, however, would demand careful evaluation due to the expressive rates of lymph node metastasis in this population – an exclusion criterion to this strategy – which is especially important in males and young patients. Since most AS cohorts were conducted in high-resource settings, Latin-American patients’ acceptability and engagement on AS strategy should also be considered and clarified during treatment for a shared decision-making [38]. Some limitations of our study should be acknowledged. Due to its retrospective nature, inherent bias may be present. Moreover, since only patients of a single thyroid cancer reference center were studied, selection bias cannot be ruled out. The single center model, on the other hand, brings uniformity and homogeneity to the methods implemented in the study. Our institution represents a real-ground clinical practice in Latin America – where data is still needed to understand PTMC patient presentation and evolution. Additionally, since many patients were treated following previous guidelines, 245 patients underwent TT and only 2 underwent lobectomy, and a substantial portion received RAI therapy (60.9%). Although less aggressive treatment approaches have already been demonstrated as equally effective alternatives in selected cases [39, 40], TT is still extensively overused worldwide, even in tumors ≤2cm. RAI therapy, with current limited indications by the ATA 2015 guidelines, is still widely used in patients with low-risk disease [16, 17]. Considering that up to 80% of recurrences occur during 3-5 years after initial treatment, our median follow-up of 5.5 years seems adequate to evaluate long-term disease status [41]. In conclusion, we found a significant proportion of PTMC in a DTC cohort from a thyroid cancer reference center. The PTMC excellent outcomes occurred despite type of diagnosis, and at the expense of high rates of surgical complications. Since nonincidental diagnosis, male sex, and younger age were predictors of lymph node metastasis (which, in turn, is a predictor of persistent disease) we believe that this group of patients must be evaluated more carefully before AS be considered. Comprehensive consideration of tumor and patient profile, treatment prognosis, and treatment-related adverse effects should, altogether, be considered and conveyed during the shared decision-making process with PTMC patients. Declarations Acknowledgements We thank the iPoint-systems gmbh for the courtesy license to access and use e!Sankey Software to build our figures. We also thank the below funding institutions for supporting this scientific research. Funding Our study was supported by the Fundação de Amparo à Pesquisa do estado do Rio Grande do Sul (FAPERGS), Fundo de Incentivo à Pesquisa e Eventos do Hospital de Clínicas de Porto Alegre (FIPE/HCPA) and Programa Institucional de Bolsas de Iniciação Científica da Universidade Federal do Rio Grande do Sul (PIBIC/UFRGS). Contributions All authors contributed to the study conception and design. Material preparation and data collection were performed by Henrique C. Scherer, Paula Fernandes and Rafael S. Scheffel. Data analysis was performed by Henrique C. Scherer and Jose M. Dora. The first draft of the manuscript was written by Henrique C. Scherer and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Ethics declarations Competing interests The authors have no relevant financial or non-financial interests to disclose. Ethics approval Approval was obtained from the ethics committee of Hospital de Clínicas de Porto Alegre (CAAE 3095.4520.600005327/GPPG 2020-0182). The procedures used in this study adhere to the tenets of the Declaration of Helsinki. Consent to participate Informed consent was obtained from all individual participants included in the study. Consent for publication The authors of the study have consent and responsibility for submission to the journal. References Davies L, Welch HG.: Increasing Incidence of Thyroid Cancer in the United States, 1973-2002. Journal of the American Medical Association (2006). https://doi:10.1001/jama.295.18.2164 Davies L, Welch HG.: Current thyroid cancer trends in the United States. Journal of the American Medical Association Otolaryngology-- Head & Neck Surgery (2014). https://doi:10.1001/jamaoto.2014.1 Ahn HS, Kim HJ, Welch HG.: Korea’s Thyroid-Cancer “Epidemic” — Screening and Overdiagnosis. New England Journal of Medicine (2014). https://doi:10.1056/nejmp1409841 La Vecchia C, Malvezzi M, Bosetti C, et al.: Thyroid cancer mortality and incidence: A global overview. International Journal of Cancer (2014). https://doi:10.1002/ijc.29251 Vaccarella S, Dal Maso L, Laversanne M, Bray F, Plummer M, Franceschi S.: The Impact of Diagnostic Changes on the Rise in Thyroid Cancer Incidence: A Population-Based Study in Selected High-Resource Countries. Thyroid (2015). https://doi:10.1089/thy.2015.0116 Li M, Brito JP, Vaccarella S.: Long-Term Declines of Thyroid Cancer Mortality: An International Age–Period–Cohort Analysis. Thyroid (2020). https://doi:10.1089/thy.2019.0684 Morris LGT, Sikora AG, Tosteson TD, Davies L.: The Increasing Incidence of Thyroid Cancer: The Influence of Access to Care. Thyroid (2013). https://doi:10.1089/thy.2013.0045 Haymart MR, Banerjee M, Reyes-Gastelum D, Caoili E, Norton EC.: Thyroid Ultrasound and the Increase in Diagnosis of Low-Risk Thyroid Cancer. The Journal of Clinical Endocrinology & Metabolism (2018). https://doi:10.1210/jc.2018-01933 Brito JP, Morris JC, Montori VM.: Thyroid cancer: zealous imaging has increased detection and treatment of low risk tumours. British Medical Journal (2013). https://doi:10.1136/bmj.f4706 Vaccarella S, Franceschi S, Bray F, Wild CP, Plummer M, Dal Maso L.: Worldwide Thyroid-Cancer Epidemic? The Increasing Impact of Overdiagnosis. New England Journal of Medicine (2016). https://doi:10.1056/nejmp1604412 Hay ID, Hutchinson ME, Gonzalez-Losada T, et al.: Papillary thyroid microcarcinoma: A study of 900 cases observed in a 60-year period. Surgery (2008). https://doi:10.1016/j.surg.2008.08.035 Miyauchi A.: Clinical Trials of Active Surveillance of Papillary Microcarcinoma of the Thyroid. World Journal of Surgery (2016). https://doi:10.1007/s00268-015-3392-y Tuttle RM, Fagin JA, Minkowitz G, et al.: Natural History and Tumor Volume Kinetics of Papillary Thyroid Cancers During Active Surveillance. Journal of the American Medical Association Otolaryngology–Head & Neck Surgery (2017). https://doi:10.1001/jamaoto.2017.1442 Oda H, Miyauchi A, Ito Y, et al.: Comparison of the costs of active surveillance and immediate surgery in the management of low-risk papillary microcarcinoma of the thyroid. Endocrine Journal (2017). https://doi:10.1507/endocrj.ej16-0381 Kong SH, Ryu J, Kim MJ, et al.: Longitudinal Assessment of Quality of Life According to Treatment Options in Low-Risk Papillary Thyroid Microcarcinoma Patients: Active Surveillance or Immediate Surgery (Interim Analysis of MAeSTro). Thyroid (2019). https://doi:10.1089/thy.2018.0624 Wang TS, Goffredo P, Sosa JA, Roman SA.: Papillary Thyroid Microcarcinoma: An Over-Treated Malignancy? World Journal of Surgery (2014). https://doi:10.1007/s00268-014-2602-3 Moten AS, Zhao H, Willis AI.: The overuse of radioactive iodine in low-risk papillary thyroid cancer patients. Surgical Oncology (2019). https://doi:10.1016/j.suronc.2019.05.011 Scheffel RS, Zanella AB, Dora JM, Maia AL.: Timing of Radioactive Iodine Administration Does Not Influence Outcomes in Patients with Differentiated Thyroid Carcinoma. Thyroid (2016). https://doi:10.1089/thy.2016.0038 Nava CF, Scheffel RS, Zanella AB, Zelmanovitz F, Maia AL, Dora JM.: Reappraising the Diagnostic Accuracy of Post-Treatment Whole-Body Scans for Differentiated Thyroid Carcinoma. Hormone and Metabolic Research (2020). https://doi:10.1055/a-1212-8594 Nava CF, Zanella AB, Scheffel RS, Maia AL, Dora JM.: Impact of the updated TNM staging criteria on prediction of persistent disease in a differentiated thyroid carcinoma cohort. Archives of Endocrinology and Metabolism (2019). https://doi:10.20945/2359-3997000000097 Cooper DS, Doherty GM, Haugen BR, et al.: Revised American Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid (2009). https://doi:10.1089/thy.2009.0110 Haugen BR, Alexander EK, Bible KC, et al.: 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid (2016). https://doi:10.1089/thy.2015.0020 Momesso DP, Tuttle RM.: Update on Differentiated Thyroid Cancer Staging. Endocrinology and Metabolism Clinics of North America (2014). https://doi:10.1016/j.ecl.2014.02.010 Tuttle RM, Tala H, Shah J, et al.: Estimating Risk of Recurrence in Differentiated Thyroid Cancer After Total Thyroidectomy and Radioactive Iodine Remnant Ablation: Using Response to Therapy Variables to Modify the Initial Risk Estimates Predicted by the New American Thyroid Association Staging System. Thyroid (2010). https://doi:10.1089/thy.2010.0178 Vaisman F, Momesso D, Bulzico DA, et al.: Spontaneous remission in thyroid cancer patients after biochemical incomplete response to initial therapy. Clinical Endocrinology (2012). https://doi:10.1111/j.1365-2265.2012.04342.x Brandi ML, Bilezikian JP, Shoback D, et al.: Management of Hypoparathyroidism: Summary Statement and Guidelines. The Journal of Clinical Endocrinology & Metabolism (2016). https://doi:10.1210/jc.2015-3907 Roti E, degli Uberti EC, Bondanelli M, Braverman LE.: Thyroid papillary microcarcinoma: a descriptive and meta-analysis study. European Journal of Endocrinology (2008). https://doi:10.1530/eje-07-0896 Liu LS, Liang J, Li JH, et al.: The incidence and risk factors for central lymph node metastasis in cN0 papillary thyroid microcarcinoma: a meta-analysis. European Archives of Oto-Rhino-Laryngology (2016). https://doi:10.1007/s00405-016-4302-0 Zhang L, Wei W, Ji Q, et al.: Risk Factors for Neck Nodal Metastasis in Papillary Thyroid Microcarcinoma: A Study of 1066 Patients. The Journal of Clinical Endocrinology & Metabolism (2012). https://doi:10.1210/jc.2011-1546 Ito Y, Miyauchi A, Kihara M, Higashiyama T, Kobayashi K, Miya A.: Patient Age Is Significantly Related to the Progression of Papillary Microcarcinoma of the Thyroid Under Observation. Thyroid (2014). https://doi:10.1089/thy.2013.0367 Sugitani I.: Active surveillance of low-risk papillary thyroid microcarcinoma. Best Practice & Research Clinical Endocrinology & Metabolism (2022). https://doi:10.1016/j.beem.2022.101630 Mehanna H, Al-maqbili T, Carter B, et al.: Differences in the Recurrence and Mortality Outcomes Rates of Incidental and Nonincidental Papillary Thyroid Microcarcinoma: A Systematic Review and Meta-Analysis of 21 329 Person-Years of Follow-up. The Journal of Clinical Endocrinology & Metabolism (2014). https://doi:10.1210/jc.2013-2118 Domínguez JM, Nilo F, Martínez MT, et al. Papillary thyroid microcarcinoma: characteristics at presentation, and evaluation of clinical and histological features associated with a worse prognosis in a Latin American cohort. Archives of Endocrinology and Metabolism (2018). https://doi:10.20945/2359-3997000000013 Leboulleux S, Tuttle RM, Pacini F, Schlumberger M.: Papillary thyroid microcarcinoma: time to shift from surgery to active surveillance? The Lancet Diabetes & Endocrinology (2016). https://doi:10.1016/s2213-8587(16)30180-2 Sawka AM, Ghai S, Yoannidis T, et al.: A Prospective Mixed-Methods Study of Decision-Making on Surgery or Active Surveillance for Low-Risk Papillary Thyroid Cancer. Thyroid (2020). https://doi:10.1089/thy.2019.0592 Sasaki T, Miyauchi A, Ito Y, et al.: Marked Decrease Over Time in Conversion Surgery After Active Surveillance of Low-Risk Papillary Thyroid Microcarcinoma. Thyroid (2020). https://doi:10.1089/thy.2020.0319 Oda H, Miyauchi A, Ito Y, et al.: Incidences of Unfavorable Events in the Management of Low-Risk Papillary Microcarcinoma of the Thyroid by Active Surveillance Versus Immediate Surgery. Thyroid (2016). https://doi:10.1089/thy.2015.0313 Smulever A, Pitoia F.: Active surveillance in papillary thyroid carcinoma: not easily accepted but possible in Latin America. Archives of Endocrinology and Metabolism (2019). https://doi:10.20945/2359-3997000000168 Sosa JA.: Extent of Surgery for Papillary Thyroid Cancer Is Not Associated with Survival: An Analysis of 61,775 Patients. VideoEndocrinology (2014). https://doi:10.1089/ve.2014.0026 Welch HG, Doherty GM.: Saving Thyroids — Overtreatment of Small Papillary Cancers. New England Journal of Medicine (2018). https://doi:10.1056/nejmp1804426 Durante C, Montesano T, Torlontano M, et al.: Papillary Thyroid Cancer: Time Course of Recurrences During Postsurgery Surveillance. The Journal of Clinical Endocrinology & Metabolism (2013). https://doi:10.1210/jc.2012-3401 tables Table 1. Characteristics of the 257 patients with PTMC who underwent total thyroidectomy and 2 who underwent lobectomy. Female sex – n (%) 216 (84.0) Age at diagnosis (years) 48.3 ± 13.5 Tumor size (cm) 0.68 ± 0.26 Multicentric – n (%) 78 (30.4) Lymph node metastasis – n (%) N0 153 (59.6) N1 63 (24.5) Nx 41 (16.0) Distant metastasis – n (%) 1 (0.4) TNM AJCC stage – n (%) I 241 (93.8) II 16 (6.2) American Thyroid Association 2009 Risk Stratification System – n (%) Low 170 (66.1) Intermediate 86 (33.5) High 1 (0.4) Radioiodine – n (%) 156 (60.7) Radioiodine Activity (mCi) 88.3 ± 34.5 Adverse Surgical Outcomes – n (%) Permanent hypoparathyroidism 20 (7.8) Persistent subjective voice disturbance 14 (5.4) Any surgical complication 31 (12.1) Dynamic response to therapy stratification after initial treatment – n (%) Excellent response 130 (58.0) Indeterminate response 74 (33.0) Biochemical incomplete response 10 (4.5) Cervical structural incomplete response 9 (4.0) Distant structural incomplete response 1 (0.4) Dynamic response to therapy stratification at last follow-up – n (%) Excellent response 147 (63.1) Indeterminate response 66 (28.3) Biochemical incomplete response 11 (4.7) Cervical structural incomplete response 8 (3.4) Distant structural incomplete response 1 (0.4) Follow-up (years) 5.5 (2.5-9.7) Data are shown as number (%), mean ± SD and median (P25-P75). N0: No evidence of lymph node metastasis; N1: metastasis to lymph nodes; Nx: regional lymph nodes not accessed. TNM/AJCC: TNM staging system of the American Joint Committee on Cancer. ATA: American Thyroid Association. Table 2. Characteristics of 207* patients with PTMC who underwent total thyroidectomy and 2 who underwent lobectomy compared by modality of diagnosis. Characteristic Incidental diagnosis (n=92) Nonincidental (n=115) P- value Female – n (%) 81 (88.0) 93 (80.9) 0.161 Age at diagnosis (years) 50.4 ± 12.4 49.3 ± 14.0 0.570 Tumor size (cm) 0.60 ± 0.28 0.72 ± 0.24 0.003 Multicentric – n (%) 26 (28.3) 33 (28.9) 0.914 Lymph node metastasis – n (%) < 0.001 N0 68 (73.9) 65 (57.5) - N1 11 (11.9) 36 (31.3) - Nx 13 (14.1) 14 (12.2) - Distant metastasis – n (%) 0 (0.0) 1 (0.9) 0.370 TNM AJCC stage – n (%) 0.009 I 91 (98.9) 104 (90.4) - II 1 (1.1) 11 (9.6) - American Thyroid Association 2009 Risk Stratification System – n (%) 0.135 Low 69 (75.0) 73 (63.5) - Intermediate 23 (25.0) 41 (35.7) - High 0 (0.0) 1 (0.9) - Radioiodine – n (%) 49 (55.7) 66 (58.9) 0.685 Radioiodine activity (mCi) 82.2 ± 32.5 91.8 ± 33.8 0.144 Adverse Surgical Outcomes – n (%) - Permanent hypoparathyroidism 3 (3.3) 9 (7.9) 0.164 Persistent subjective voice disturbance 3 (3.4) 7 (6.3) 0.344 Any surgical complication 5 (5.6) 15 (13.5) 0.064 Dynamic response to therapy stratification after initial treatment – n (%) 0.811 Excellent response 44 (55.0) 57 (55.3) - Indeterminate response 30 (37.5) 35 (34.0) - Biochemical incomplete response 4 (5.0) 5 (4.9) - Cervical structural incomplete response 2 (2.5) 5 (4.9) - Distant structural incomplete response 0 (0.0) 1 (1.0) - Dynamic response to therapy stratification at last follow-up - n (%) 0.827 Excellent response 49 (59.8) 66 (63.5) - Indeterminate response 25 (30.5) 30 (28.8) - Biochemical incomplete response 5 (6.1) 4 (3.8) - Cervical structural incomplete response 3 (3.7) 3 (2.9) - Distant structural incomplete response 0 (0.0) 1 (1.0) - Follow-up (years) 5.2 (1.8-8.7) 5.0 (2.5-7.6) 0.490 * We could not classify 50 patients as incidental or nonincidental diagnosis. Data are shown as number (%), mean ± SD and median (P25-P75). N0: No evidence of lymph node metastasis; N1: metastasis to lymph nodes; Nx: regional lymph nodes not accessed. TNM/AJCC: TNM staging system of the American Joint Committee on Cancer. ATA: American Thyroid Association. Table 3. Univariate analysis of predictors of persistent disease. Disease Status Excellent/Indeterminate (n=213) Persistent disease (n=20) P Male– n (%) 28 (13.1) 6 (30.0) 0.041 Age at diagnosis (years) 49.1 ± 12.7 42.6 ± 14.3 0.110 Tumor size (cm) 0.69 ± 0.25 0.60 ± 0.25 0.659 Multicentricity – n (%) 61 (28.6) 9 (45.0) 0.135 Nodal metastasis – n (%) 44 (20.7) 12 (60.0) <0.001 TNM AJCC stage – n (%) 0.133 I 200 (93.9) 17 (85.0) II 13 (6.1) 3 (15.0) American Thyroid Association Risk Stratification System 2009 – n (%) <0.001 Low 151 (70.9) 5 (25.0) Intermediate 62 (29.1) 14 (70.0) High 0 (0.0) 1 (5.0) Radioiodine use – n (%) 132 (62.0) 13 (65.0) 0.388 Radioiodine activity (mCi) 86.9 ± 34.2 89.8 ± 39.6 0.775 Dynamic response to therapy after initial treatment – n (%) <0.001 Excellent 128 (60.1) 2 (10.0) Indeterminate 72 (33.3) 3 (15.0) Biochemical incomplete response 4 (1.9) 6 (30.0) Cervical structural incomplete response 3 (1.4) 6 (30.0) Distant structural incomplete response 0 (0.0) 1 (5.0) Unknown 7 (3.3) 2 (10.0) Nonincidental diagnosis – n (%) 96 (45.1) 8 (40.0) 0.883 Data are shown as number (%), mean ± SD and median (P25-P75) TNM/AJCC: TNM staging system of the American Joint Committee on Cancer. ATA: American Thyroid Association. Table 4. Multivariate analysis of predictors of lymph node metastasis and persistent disease. RR [95%CI] P Predictors of lymph node metastasis Male sex 2.30 [1.51 – 3.52] <0.001 Age at diagnosis (years) 0.97 [0.96 – 0.99] <0.001 Tumor size 0.60 [0.93 – 1.14] 0.599 Multicentricity 1.00 [0.62 – 1.62] 0.970 Nonincidental diagnosis 2.17 [1.20 – 3.92] 0.010 Predictors of persistent disease Male sex 1.75 [0.59 – 5.15] 0.304 Age at diagnosis (years) 0.95 [0.90 – 1.01] 0.089 Tumor size 0.82 [0.64 – 1.06] 0.135 Multicentricity 2.42 [1.04 – 5.60] 0.039 Nodal metastasis 4.48 [1.60 – 12.30] 0.004 Nonincidental diagnosis 2.19 [0.91 – 5.26] 0.078 RR: relative risk. CI: confidence interval. Table 5. Univariate analysis of predictors of lymph node metastasis. Nodal metastasis Absent (n=153) Detected (n=63) P Male– n (%) 13 (8.5) 24 (38.1) <0.001 Age at diagnosis (years) 50.6 ± 12.3 41.1 ± 12.8 <0.001 Tumor size (cm) 0.68 ± 0.26 0.73 ± 0.22 0.235 Multicentric – n (%) 44 (28.8) 27 (42.9) 0.048 Type of diagnosis – n (%) <0.001 Nonincidental 65 (42.5) 36 (57.1) Incidental 68 (44.4) 11 (17.4) Not categorized 20 (13.1) 16 (25.5) Data are shown as number (%), mean ± SD and median (P25-P75). Supplementary Files ESM1.pdf Cite Share Download PDF Status: Posted Version 1 posted 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1880064","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":124576493,"identity":"05a2d0fa-5ccf-42ca-b6c4-3c4deecabaaa","order_by":0,"name":"Henrique Cabral Scherer","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDElEQVRIiWNgGAWjYBACAxCRAGGzgUl+sEgBKVokG0AiBgS0MCBrMTiALo4GzNl7j314UHZYjr//8LMHH/fY5BufX5344YEBgzy/2AGsWix7ziXPSDh32FjiRpq54YxnaZbbbrzdLAF0mOHM2QnYHXYjx5ghse1w4gYJHjZpngOHDcxunN0A0pJgcBuHlvtvwFrqN/CfYZP+c+C/gfGMs5t/4NVygwesBagmh02a4cABAwP+3m34bTkDdFjCuXTDGTfSzCR7DiQbSNzg3WaRYCCB2y/Hzxgz/iizlgeFmMSPA3YG/P1nN9/8UWEjzy+NXQsEsCFzJMAqJfAox9DCf4CA6lEwCkbBKBhpAACPqGBXJNNO6wAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0001-6620-0054","institution":"Hospital de Clinicas de Porto Alegre","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Henrique","middleName":"Cabral","lastName":"Scherer","suffix":""},{"id":124576494,"identity":"2f6513b3-2f99-4288-871e-65bfd404b684","order_by":1,"name":"Paula Fernandes","email":"","orcid":"","institution":"Hospital de Clinicas de Porto Alegre","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Paula","middleName":"","lastName":"Fernandes","suffix":""},{"id":124576495,"identity":"f2ca6580-fe95-4386-b662-89899e659e4b","order_by":2,"name":"Rafael Selbach Scheffel","email":"","orcid":"","institution":"Hospital de Clinicas de Porto Alegre","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Rafael","middleName":"Selbach","lastName":"Scheffel","suffix":""},{"id":124576496,"identity":"d487135c-684f-448f-b822-4b1784e8e1ca","order_by":3,"name":"André B. Zanella","email":"","orcid":"","institution":"Hospital de Clinicas de Porto Alegre","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"André","middleName":"B.","lastName":"Zanella","suffix":""},{"id":124576497,"identity":"c1c2ae92-0060-4713-b60c-6e84b72cd0e4","order_by":4,"name":"Ana Luiza Maia","email":"","orcid":"","institution":"Hospital de Clinicas de Porto Alegre","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ana","middleName":"Luiza","lastName":"Maia","suffix":""},{"id":124576498,"identity":"552bb552-65db-4cad-ab05-5e203b33c640","order_by":5,"name":"Jose Miguel Dora","email":"","orcid":"","institution":"Hospital de Clinicas de Porto Alegre","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jose","middleName":"Miguel","lastName":"Dora","suffix":""}],"badges":[],"createdAt":"2022-07-21 04:25:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1880064/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1880064/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":24611195,"identity":"a749cbe4-6ad3-48d4-9d42-f330c259ea62","added_by":"auto","created_at":"2022-08-01 17:03:29","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":80013,"visible":true,"origin":"","legend":"\u003cp\u003eEvolution of 224 PTMC patients stratified by ATA risk for recurrence and dynamic response to therapy, both at initial treatment and at last follow-up. Line’s trajectory represents patient evolution and thickness represents the number of patients.\u003c/p\u003e\u003cp\u003eATA: American Thyroid Association\u003c/p\u003e\u003cp\u003eDRS: dynamic risk stratification\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-1880064/v1/acfc7453476cb72b1983b5ae.png"},{"id":24610816,"identity":"a97c6fc1-a88e-4a96-a027-0439f1c795e7","added_by":"auto","created_at":"2022-08-01 16:58:29","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":194046,"visible":true,"origin":"","legend":"\u003cp\u003ePercentage of lymph node metastasis stratified by age groups.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-1880064/v1/62e45902845d8c27c5d7d072.jpeg"},{"id":25765126,"identity":"b4f02d5f-e2e1-4d3b-b896-1b0195f9c2d8","added_by":"auto","created_at":"2022-08-28 21:12:40","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":703435,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1880064/v1/dadc80d5-7aa1-4356-afc3-0e18f4887eb0.pdf"},{"id":24610818,"identity":"8a895a9d-bb41-4407-9b4f-9e11645daa4d","added_by":"auto","created_at":"2022-08-01 16:58:29","extension":"pdf","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":53542,"visible":true,"origin":"","legend":"","description":"","filename":"ESM1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1880064/v1/63b709efaa75ac93bba7973f.pdf"}],"financialInterests":"","formattedTitle":"Papillary thyroid microcarcinoma: insights from a cohort of 257 thyroidectomized patients","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThyroid carcinomas are the most common malignancy of the endocrine system, being responsible for nearly 2% of all cancer cases. In the last decades, thyroid cancer incidences increased worldwide [1-5], up to 15-fold in countries that adopted screening programs [3], and with substantial variability between and within populations. Mortality rates, however, remained stable or even decreased in most countries [1-3, 6]. Papillary thyroid carcinoma (PTC), the histologic type that accounts for more than 85% of thyroid carcinomas, has been shown to be responsible for most of thyroid cancer incidence\u0026rsquo;s growth [1, 2]. Almost half of new PTC cases can be due to small tumors with 10 mm or smaller diameter, called microcarcinomas (PTMC) [1]. Possibly due to enhanced healthcare access and increased sensitivity of diagnostic imaging methods [7-9], this data raised concerns on the risk of overdiagnosing PTC [5, 10], especially in PTMC cases, in which the tumors present favorable prognosis [11].\u003c/p\u003e\n\u003cp\u003eGiven the surgical risks and potential consequences associated with thyroidectomies \u0026ndash; such as vocal cord paralysis (VCP), hypoparathyroidism (Hypo-PT), and need for levothyroxine substitution \u0026ndash; current recommendations point to the increasing relevance of more conservative treatment options. In this context, thyroid lobectomy and active surveillance (AS) emerge as safe and effective options for selected cases, with excellent clinical outcomes in long-term follow-up [12,13]. Moreover, these new approaches brought relevant discussion of PTMC decision-making process and its impact in several issues, including quality of life and healthcare costs [14, 15]. Nevertheless, current PTMC treatment approaches are predominantly aggressive worldwide, regarding surgical decisions and radioiodine (RAI) use, despite new evidence and guidelines [16, 17]. The applicability, patient selection, and decision-making between treatment options according to prognostic factors and potential benefits and risks, especially in real clinical care settings, are still a matter of study.\u003c/p\u003e\n\u003cp\u003eIn this study, we aim to gather insights on PTMC management and treatment perspectives in a cohort study of PTMC patients that underwent total thyroidectomy. We also explored if the clinical course and outcomes were different in PTMC classified as incidental and as nonincidental based on the diagnosis after and before surgery, respectively.\u003c/p\u003e"},{"header":"Materials And Methods","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003ePatients and study design\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients from a cohort of differentiated thyroid cancer (DTC) were followed at the Thyroid Unit, Endocrine Division of Hospital de Cl\u0026iacute;nicas de Porto Alegre (HCPA) \u0026ndash; a tertiary care, university teaching hospital in southern Brazil. From 2000 to 2019, all consecutive patients with a histological diagnosis of PTC with a tumor size \u0026le; 10mm were included. Patients were classified with nonincidental diagnosis when the index nodule investigated had malignancy confirmed by fine needle aspiration biopsy (FNAB) or high suspicion for malignancy prior to surgical intervention decision, with confirmatory histopathological results. Incidental diagnosis was defined as diagnosis of PTC made in histopathological examination after thyroid surgery for other reasons.\u003c/p\u003e\n\u003cp\u003eThe study was approved by the ethics committee of the institution (CAAE 3095.4520.600005327/GPPG 2020-0182).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eTreatment protocol and follow-up\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll patients underwent thyroidectomy, some of them were referred to our Thyroid Unit after undergoing surgery in other institutions. Decisions regarding cervical lymph node dissection were made at the discretion of the surgical team at the Institution where the procedure was performed. The radioiodine (RAI) administration protocol used activities prescribed at the attending physician\u0026rsquo;s discretion. RAI was administered in a stimulated thyrotropin (TSH) condition of endogenous hypothyroidism (TSH \u0026gt;30 mUI/L), after withdrawing levothyroxine for at least 3-4 weeks [18]. A post-treatment whole body scan (post-treatment WBS) was performed seven to ten days after RAI administration [19].\u003c/p\u003e\n\u003cp\u003eIn the first evaluation, the following data were recorded for each patient: demographics, tumor characteristics including histological features, extension and lymph node involvement, and treatment (e.g., surgery, RAI remnant ablation, and other interventions). Each patient was classified using the 8\u003csup\u003eth\u003c/sup\u003e edition of the TNM/AJCC staging system (I, II, III, or IV) [20]. The \u0026ldquo;no evidence of lymph node metastasis\u0026rdquo; (N0) status was determined by clinical examination of the neck, preoperative and postoperative neck ultrasound (US) imaging, or by macroscopic examination during surgery and pathological examination of patients with lymph node resection.\u003c/p\u003e\n\u003cp\u003eDistant metastasis (M1) was considered present when there was a lesion outside the cervical bed on imaging computed tomography (CT), or scintigraphy with histological confirmation, or post-treatment WBS uptake and/or elevated thyroglobulin (Tg). The risk of persistent/recurrent disease was assessed based on the proposed risk stratification system by the 2009 American Thyroid Association (ATA) guidelines, with patients classified into three risk groups: low, intermediate, and high [21].\u003c/p\u003e\n\u003cp\u003eThe follow-up protocol called for an initial assessment at 3 to 6 months after the initial treatment, which included a physical examination of the neck and measurements of the serum Tg levels under TSH suppression (Tg-T4) and anti-thyroglobulin antibody (TgAb). In a second evaluation, 6 to 12 months after the initial treatment, physical examination of the neck and serum TSH, Tg-T4, and TgAb were reassessed. Some patients also had the serum level of Tg evaluated under stimulated TSH condition of endogenous hypothyroidism (TSH\u0026gt;30 mIU/L) (sTg) at the end of the first year of follow-up. Neck US was performed in this first year of follow-up. At this point, the patient was classified according to disease response to initial therapy (see below in the outcomes section). Patients classified as having an excellent response were scheduled for annual visits, during which a physical examination of the neck and measurements of TSH, Tg-T4, and TgAb were performed. Patients with indeterminate response or persistent disease were scheduled for the same examination at least twice a year. Additional imaging studies [e.g., x-ray, bone scintigraphy, CT] were performed, as needed, whenever the clinical or laboratory findings raised the suspicion of persistent or recurrent disease. Duration of follow-up was defined as the time between the first surgery and the last medical visit to the clinic.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eOutcomes\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDynamic response to therapy status was defined based on clinical examination, Tg-T4 and/or sTg levels, neck US, post-RAI WBS (when available), and additional imaging exams when indicated. Patients were classified into four categories: excellent response, indeterminate response, biochemical incomplete response, or structural incomplete response [22, 23].\u003c/p\u003e\n\u003cp\u003eIn patients submitted to RAI, excellent response was defined as negative imaging and Tg-T4 \u0026lt;0.2 ng/mL or sTg \u0026lt;1.0 ng/mL. Biochemical incomplete response was defined as negative imaging and Tg-T4 \u0026gt;1.0ng/mL or sTg \u0026gt;10.0 ng/mL or rising TgAb levels. Structural incomplete response was defined as structural or functional evidence of disease with any Tg or TgAb level. Indeterminate response was defined as non-specific findings on imaging studies or Tg-T4 between 0.2 to 1.0 ng/mL, sTg between 1.0 and 10.0 ng/mL, or positive TgAb with stable or declining levels [22].\u003c/p\u003e\n\u003cp\u003eIn patients who underwent total thyroidectomy (TT) but did not receive RAI, excellent response was defined as negative imaging and Tg-T4 \u0026lt;0.2 ng/mL or sTg \u0026lt;2.0 ng/mL. Biochemical incomplete response was defined as negative imaging and Tg-T4 \u0026gt;5.0ng/mL, sTg \u0026gt;10.0 ng/mL, or increasing Tg levels over time or rising TgAb levels. Structural incomplete response was defined as structural or functional evidence of disease with any Tg or TgAb level. Indeterminate response was defined as non-specific findings on imaging studies or Tg-T4 between 0.2 to 5.0 ng/mL, sTg between 2.0 and 10.0 ng/mL, or positive TgAb with stable or declining levels [22].\u003c/p\u003e\n\u003cp\u003eFor patients who underwent lobectomy, excellent response was defined as negative imaging and stable Tg-T4 level \u0026lt;30ng/mL with undetectable TgAb [23]. Biochemical incomplete response was defined as negative imaging and Tg-T4 level \u0026gt;30ng/mL, increasing Tg level values over time with similar TSH levels, or increasing TgAb levels. Structural incomplete response was defined as structural or functional evidence of disease with any Tg or TgAb level. Indeterminate response was defined as non-specific findings on imaging studies, positive TgAb levels stable, or declining in the absence of structural or functional disease [23].\u003c/p\u003e\n\u003cp\u003eFor treatment response analysis, persistent disease was defined as either incomplete biochemical, cervical structural incomplete, or distant structural incomplete responses. Indeterminate response was combined with excellent response outcome, due to their similar prognosis after treatment, with 80-85% of these patients remaining either stable or improving to excellent response [24, 25].\u003c/p\u003e\n\u003cp\u003eRegarding surgical complications, permanent Hypo-PT was defined as hypocalcemia and low parathormone levels (PTH\u0026lt;20 pg/mL) for more than 1 year after surgery; this period was chosen, rather than the 6 months period of current guidelines [26], aiming for more conservative and accurate event rate report of long-term complications. Patients with no preoperative voice symptoms who presented with complaints of deficiency or quality alterations on voice for more than 1 year after surgery were considered to have persistent subjective voice disturbance (PSVD). Any surgical complication was defined as permanent Hypo-PT and/or PSVD.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eLaboratory analysis\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSerum Tg measurements were conducted using immunoradiometric assays: radioimmunoassay (COBRA II) from 2000 to 2002; electrochemiluminescence (ELECSYS 2010, Elecsys TG, Roche, Switzerland - analytical sensitivity of 1.0 ng/mL) from 2002 to 2005; electrochemiluminescence (MODULAR E-170, Elecsys TG, Roche, Switzerland- analytical sensitivity of 1.0 ng/mL) from 2005 to 2010; and chemiluminescence (Immulite XPI 2000, Siemens, Germany \u0026ndash; analytical sensitivity of 0.2 ng/mL) from 2010 until the present. Serum TgAb levels were measured using the passive agglutination method from 2000 to 2010 (U-shaped microplates, Serodia-ATG, Japan \u0026ndash; analytical sensitivity of 1/100); chemiluminescence from 2010 to 2018 (Architect ci 4100, Abbott, United States \u0026ndash; analytical sensitivity 1.0 UI/mL); and chemiluminescence from 2019 until the present (DXI UNICEL 800, Beckman Coulter, United States \u0026ndash; analytical sensitivity \u0026lt;0.9 UI/mL). TSH levels were measured by chemiluminescence assay from 2000 to 2006 (Immulite 2000 SIEMENS, Munich, Germany), electrochemiluminescence from 2006 to 2010 (Modular E ROCHE, Basel, Switzerland), chemiluminescence assay from 2010 to 2014 (Centaur XP SIEMENS, Munich, Germany), electrochemiluminescence from 2014 to 2019 (Cobas E602 ROCHE, Basel, Switzerland), and chemiluminescence immunoassay (Abbot, Chicago, USA) from 2019 until the present, with RV 0.35-4.94 mUI/L.\u003c/p\u003e\n\u003cp\u003eSerum PTH was evaluated by chemiluminescent microparticle immunoassay method through the ARCHITECT ci 4100 equipment (Abbott Diagnostics, Abbott Park, IL, USA), with reference values (RV) of 15.0\u0026ndash;68.3 pg/mL; intra-assay and inter-assay coefficients of variation were 6.1 and 6.4%, respectively. Total serum calcium was evaluated by the NM-BAPTA method and corrected by albumin levels (corrected calcium = 0.8 \u0026times; [4.0\u0026minus;serum albumin] + serum calcium) with RV 8.6 to 10.0 mg/dL. Serum phosphorus was evaluated by the Molybdate UV and colorimetric (xylidyl blue) methods, with RV 2.5\u0026ndash;4.5 mg/dL. The electrolyte tests were made using Cobas 8000 c702 equipment (Roche Diagnostics, Indianapolis, IN, USA).\u003c/p\u003e\n\u003cp\u003eAfter each new assay had been implemented, the necessary procedures for standardization and validation were performed. These tests were all conducted in the central laboratory of HCPA.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStatistical analysis\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe clinical and laboratory data are reported as the mean \u0026plusmn; standard deviation (SD) values or as the median and percentiles 25 and 75 (P25-75) for continuous variables, and as absolute numbers and percentages for categorical variables. Statistical analyses were performed using Pearson chi-square and Fisher\u0026rsquo;s exact test for categorical variables, and Student\u0026rsquo;s t-test and Mann-Whitney U-test for continuous variables, as appropriate. For multivariate analysis models, Poisson regression was used, in which relative risk (RR) represented likelihood of associated events with a confidence interval (CI) of 95%.\u003c/p\u003e\n\u003cp\u003eAll tests were two-tailed, and all analyses were performed using the Statistical Package for Social Science Professional software version 20.0 (IBM Corp., Armonk, NY). A two-tailed P\u0026lt;0.05 was considered statistically significant. The e!Sankey software (iPoint-systems gmbh., Reutlingen, Germany) was used to build figures.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003ePatients\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 257 (23.5%) patients amongst the 1,091 patients of the institutional DTC cohort had PTC smaller or equal to 10 mm. Of these 257 PTMC patients, 84.0% were female, and the mean age of diagnosis was 48.3 \u0026plusmn; 13.5 years (Table 1). The mean tumor size was 0.68 \u0026plusmn; 0.26 cm, and 30.4% of them presented multicentric disease. 63 (24.5%) patients had nodal dissemination of the disease, and only 1 patient had distant metastasis (0.4%), which occurred in the lungs. Most patients, n=241 (93.8%), were classified as TNM Stage I, and 16 (6.2%) as TNM Stage II. Regarding 2009 ATA Risk Stratification System, 170 (66.1%) were classified as low risk, 86 (33.5%) as intermediate risk, and 1 (0.4%) as high risk. All patients underwent TT, with exception of 2 lobectomies. 156 (60.7%) patients received RAI therapy, with a mean RAI activity of 88.3 \u0026plusmn; 34.5 mCi.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eN\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e\u003cem\u003eonincidental versus incidental diagnosis\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe pre-surgical clinical evaluation was available for 207 patients: 115 (55.6%) were classified as nonincidental diagnosis, and 92 (44.4%) as incidental (Table 2). Nonincidental diagnosis, when compared with incidental diagnosis, was associated with larger tumors (0.72 \u0026plusmn; 0.24 and 0.60 \u0026plusmn; 0.28 cm, respectively, P=0.003), more frequent cervical metastasis (36 (31.3%) and 11 (11.9%), respectively, P=0.001), and a larger proportion of TNM stage II classification (11 (9.6%) and 1 (1.1%), respectively, P=0.009). No difference in the proportion of RAI prescription was observed between incidental and nonincidental groups (49 (55.7%) and 66 (58.9%), respectively, P=0.685); The RAI activity dose was also similar between the groups (82.2 \u0026plusmn; 32.5 and 91.8 \u0026plusmn; 33.8 mCi, respectively, P=0.144).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eClinical outcomes and lymph node metastasis predictors\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe dynamic response to therapy after initial treatment was defined in 224 patients (Table 1), with an excellent response observed in 130 (58.0%) patients, indeterminate response in 74 (33.0%), biochemical incomplete response in 10 (4.5%), cervical structural incomplete response in 9 (4.0%), and distant structural incomplete response in 1 (0.4%). The patient with M1, classified as ATA high-risk, was a 40-year-old male with a 0.4 cm (larger nodule) multicentric tumor, who presented lateral cervical lymph node and distant lung metastasis.\u003c/p\u003e\n\u003cp\u003eAfter a median follow-up of 5.5 years (P25-P75 2.6-9.7), the dynamic response to therapy at last follow-up of the cohort was defined for 233 patients: excellent response was observed in 147 (63.1%) patients, indeterminate response in 66 (28.3%), biochemical incomplete response in 11 (4.7%), cervical structural incomplete response in 8 (3.4%), and distant structural incomplete response in only 1 (0.4%). Figure 1\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003edepicts the patients\u0026rsquo; dynamic response to therapy evolution between initial response to treatment and at last follow-up. During this period, 27 (12.0%) patients improved their response to therapy status, 185 (82.5%) remained in the same stratum, and 12 (5.3%) worsened response to therapy status.\u003c/p\u003e\n\u003cp\u003eThe characteristics and tumor features of the 20 patients with persistent disease \u0026ndash; incomplete biochemical, cervical structural incomplete, and distant structural incomplete responses \u0026ndash; are listed in the Supplementary Table 1. Predictors of persistent disease at univariate analysis for the 20 patients with this classification at last follow-up included male sex (P=0.041), lymph node metastasis (P\u0026lt;0.001), more advanced ATA risk stratification system classification (P\u0026lt;0.001), and persistent disease after initial treatment (P\u0026lt;0.001) (Table 3). No difference in RAI activity was observed between patients with excellent or indeterminate response versus persistent disease. No differences in treatment response were observed between the incidental and the nonincidental diagnosis groups. In multivariate analysis \u0026ndash; regarding sex, age, tumor size, multicentricity, lymph node metastasis, and type of diagnosis \u0026ndash; lymph node metastasis (P=0.004; RR=4.48, 95%CI 1.6-12.3) and multicentricity (P=0.039; RR=2.42, 95%CI 1.04-5.6) remained as predictors of persistent disease (Table 4). Nonincidental diagnosis was associated with a tendency of persistency of the disease (P=0.078; RR=2.19, 95%CI 0.91-5.26), as well as younger age (P=0.089; RR=1.05, 95%CI 0.99-1.11).\u003c/p\u003e\n\u003cp\u003eYounger age at diagnosis (P\u0026lt;0.0001), male sex (P\u0026lt;0.001), and multicentricity (P=0.048) were associated with higher rates of lymph node metastasis (Table 5). Further analysis using the multivariate models identified male sex (P\u0026lt;0.001; RR=2.30, 95%CI 1.51-3.52), younger age (P\u0026lt;0.001; RR=1.03, 95%CI 1.01-1.04) and nonincidental diagnosis (P=0.010; RR=2.17, 95%CI 1.20-3.92) as predictors of lymph node metastasis (Table 4). Each reduction in 1 year in age was associated with an increased risk of 3% for nodal metastasis. Figure 2 depicts the distribution of lymph node metastasis in different age groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eSurgical complications\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRegarding surgical complications, a total of 20 (7.8%) patients developed permanent Hypo-PT, and 14 (5.4%) suffered from PSVD. Any long-term surgical complication, defined as Hypo-PT and/or PSVD, occurred in 31 (12.1%) patients, and 3 patients suffered from both permanent Hypo-PT and PSVD. Notably, there was a tendency to more long-term surgical complications in the nonincidental diagnosis than in the incidental diagnosis group (15 [13.5%] and 5 [5.6%], respectively, P=0.062). Lymph node resection data was available for 216 patients. Permanent Hypo-PT was more frequent in patients who underwent lymph node resection compared to those who didn\u0026rsquo;t (14 (10.8%) and 2 (2.3%), P=0.02), but no association of lymph node resection with PSVD (6 (4.8%) and 5 (5.9%), P=0.72) or any surgical complication (18 (14.3%) vs 8 (9.4%), P=0.291) was observed.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe studied a cohort of patients with PTMC who underwent thyroidectomy. Among the 1,091 PTC patients of our cohort, we found a PTMC proportion similar to the literature report [27]. Moreover, we observed that 30.4% of them presented multicentric disease and 24.5% had lymph node metastasis at diagnosis. Another interesting finding is that most of the patients were disease-free after a median follow-up of 5.5 years.\u003c/p\u003e\n\u003cp\u003eThe lymph node is the main site of metastasis of PTC. In our PMTC cohort we observed in multivariate analysis that for nonincidental diagnosis, male sex and younger age were predictors of lymph node metastasis. This is consistent with previous reports that found male sex, multicentricity, and younger age to be associated with lymph node metastasis [28]. Younger age is usually associated with more advanced PTMC disease [29, 30]. In accordance with this observation, we found an association of younger age with nodal dissemination, but not with worse treatment response. Interestingly, in published active surveillance (AS) strategies, younger age is the most significant predictor of tumor growth and development of lymph node metastasis [30, 31]. All these data point to a pattern of more extensive and progressive disease in younger patients.\u003c/p\u003e\n\u003cp\u003eMost PTMC patients were classified as excellent response after the initial treatment and at last follow-up. Disease response to therapy status remained stable over time for most patients, while some demonstrated status improvement and very few progressions of disease. These findings support the long-term excellent prognosis of PTMC tumors. Both ATA risk classification (P=0.006) and dynamic risk stratification at initial treatment (P\u0026lt;0.001) were predictors of excellent response in the last follow-up, reassuring these tools as useful methods for PTMC management. Multifocality and lymph node metastasis, were associated with persistent disease at last follow-up. Although associated with larger tumors and lymph node dissemination in our cohort, nonincidental diagnosis was not associated with worse response to treatment, a finding that may be due to underpower. Notably, a recent meta-analysis found significative higher risk of recurrence in nonincidental PTMC [32]. In our study, we observed 3.8% of structural persistent disease at last follow-up (3.4% cervical) in our cohort, and available reports of structural persistence/recurrence range from 1 to 6% [27, 33, 34].\u003c/p\u003e\n\u003cp\u003eWe also observed high rates of surgical complications, represented by permanent Hypo-PT and PSVD, totaling 12.1% of any adverse event in these patients. These surgical complications have been associated with increased treatment costs within the health system [14] and worse quality of life outcomes [15], especially for permanent Hypo-PT regarding the former (due to costs of exams, hospital outpatient and inpatient visits, and pharmacological treatment) and voice disturbance regarding the latter. Since these are key factors in treatment decision-making [35], we further encourage physicians to consider local surgical complication rates to perform patient-shared and patient-centered decisions in PTMC diagnosis, aiming for better quality of life outcomes and healthcare costs.\u003c/p\u003e\n\u003cp\u003eIn this scenario of excellent clinical PTMC outcomes, AS emerges as a safe and effective option for selected cases [12,13]. Cohorts of PTMC under AS have shown that a minority of these patients evolve to surgery due to disease progression, and in these cases, despite postponement of the surgical treatment, oncological outcomes were excellent [30, 36]. In addition, AS can effectively reduce adverse events related to the management of these generally indolent tumors [37]. This is especially significant in a healthcare scenario containing a large proportion of PTMC cases and a significant risk associated with surgical treatment, such as ours. Patient selection to this approach, however, would demand careful evaluation due to the expressive rates of lymph node metastasis in this population \u0026ndash; an exclusion criterion to this strategy \u0026ndash; which is especially important in males and young patients. Since most AS cohorts were conducted in high-resource settings, Latin-American patients\u0026rsquo; acceptability and engagement on AS strategy should also be considered and clarified during treatment for a shared decision-making [38].\u003c/p\u003e\n\u003cp\u003eSome limitations of our study should be acknowledged. Due to its retrospective nature, inherent bias may be present. Moreover, since only patients of a single thyroid cancer reference center were studied, selection bias cannot be ruled out. The single center model, on the other hand, brings uniformity and homogeneity to the methods implemented in the study. Our institution represents a real-ground clinical practice in Latin America \u0026ndash; where data is still needed to understand PTMC patient presentation and evolution. Additionally, since many patients were treated following previous guidelines, 245 patients underwent TT and only 2 underwent lobectomy, and a substantial portion received RAI therapy (60.9%). Although less aggressive treatment approaches have already been demonstrated as equally effective alternatives in selected cases [39, 40], TT is still extensively overused worldwide, even in tumors \u0026le;2cm. RAI therapy, with current limited indications by the ATA 2015 guidelines, is still widely used in patients with low-risk disease [16, 17]. Considering that up to 80% of recurrences occur during 3-5 years after initial treatment, our median follow-up of 5.5 years seems adequate to evaluate long-term disease status [41].\u003c/p\u003e\n\u003cp\u003eIn conclusion, we found a significant proportion of PTMC in a DTC cohort from a thyroid cancer reference center. The PTMC excellent outcomes occurred despite type of diagnosis, and at the expense of high rates of surgical complications. Since nonincidental diagnosis, male sex, and younger age were predictors of lymph node metastasis (which, in turn, is a predictor of persistent disease) we believe that this group of patients must be evaluated more carefully before AS be considered. Comprehensive consideration of tumor and patient profile, treatment prognosis, and treatment-related adverse effects should, altogether, be considered and conveyed during the shared decision-making process with PTMC patients.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAcknowledgements\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank the \u003cem\u003eiPoint-systems gmbh\u003c/em\u003e for the courtesy license to access and use \u003cem\u003ee!Sankey Software\u003c/em\u003e to build our figures. We also thank the below funding institutions for supporting this scientific research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur study was supported by the \u003cem\u003eFunda\u0026ccedil;\u0026atilde;o de Amparo \u0026agrave; Pesquisa do estado do Rio Grande do Sul\u003c/em\u003e (FAPERGS), \u003cem\u003eFundo de Incentivo \u0026agrave; Pesquisa e Eventos do Hospital de Cl\u0026iacute;nicas de Porto Alegre\u003c/em\u003e (FIPE/HCPA) and \u003cem\u003ePrograma Institucional de Bolsas de Inicia\u0026ccedil;\u0026atilde;o Cient\u0026iacute;fica da Universidade Federal do Rio Grande do Sul\u003c/em\u003e (PIBIC/UFRGS).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eContributions\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the study conception and design. Material preparation and data collection were performed by Henrique C. Scherer, Paula Fernandes and Rafael S. Scheffel. Data analysis was performed by Henrique C. Scherer and Jose M. Dora. The first draft of the manuscript was written by Henrique C. Scherer and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics declarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCompeting interests\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEthics approval\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eApproval was obtained from the ethics committee of Hospital de Cl\u0026iacute;nicas de Porto Alegre (CAAE 3095.4520.600005327/GPPG 2020-0182). The procedures used in this study adhere to the tenets of the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eConsent to participate\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from all individual participants included in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eConsent for publication\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors of the study have consent and responsibility for submission to the journal.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eDavies L, Welch HG.: Increasing Incidence of Thyroid Cancer in the United States, 1973-2002. Journal of the American Medical Association (2006). https://doi:10.1001/jama.295.18.2164\u003c/li\u003e\n\u003cli\u003eDavies L, Welch HG.: Current thyroid cancer trends in the United States. Journal of the American Medical Association Otolaryngology-- Head \u0026amp; Neck Surgery (2014). https://doi:10.1001/jamaoto.2014.1\u003c/li\u003e\n\u003cli\u003eAhn HS, Kim HJ, Welch HG.: Korea\u0026rsquo;s Thyroid-Cancer \u0026ldquo;Epidemic\u0026rdquo; \u0026mdash; Screening and Overdiagnosis. New England Journal of Medicine (2014). https://doi:10.1056/nejmp1409841\u003c/li\u003e\n\u003cli\u003eLa Vecchia C, Malvezzi M, Bosetti C, et al.: Thyroid cancer mortality and incidence: A global overview. International Journal of Cancer (2014). https://doi:10.1002/ijc.29251\u003c/li\u003e\n\u003cli\u003eVaccarella S, Dal Maso L, Laversanne M, Bray F, Plummer M, Franceschi S.: The Impact of Diagnostic Changes on the Rise in Thyroid Cancer Incidence: A Population-Based Study in Selected High-Resource Countries. Thyroid (2015). https://doi:10.1089/thy.2015.0116\u003c/li\u003e\n\u003cli\u003eLi M, Brito JP, Vaccarella S.: Long-Term Declines of Thyroid Cancer Mortality: An International Age\u0026ndash;Period\u0026ndash;Cohort Analysis. Thyroid (2020). https://doi:10.1089/thy.2019.0684\u003c/li\u003e\n\u003cli\u003eMorris LGT, Sikora AG, Tosteson TD, Davies L.: The Increasing Incidence of Thyroid Cancer: The Influence of Access to Care. Thyroid (2013). https://doi:10.1089/thy.2013.0045\u003c/li\u003e\n\u003cli\u003eHaymart MR, Banerjee M, Reyes-Gastelum D, Caoili E, Norton EC.: Thyroid Ultrasound and the Increase in Diagnosis of Low-Risk Thyroid Cancer. The Journal of Clinical Endocrinology \u0026amp; Metabolism (2018). https://doi:10.1210/jc.2018-01933\u003c/li\u003e\n\u003cli\u003eBrito JP, Morris JC, Montori VM.: Thyroid cancer: zealous imaging has increased detection and treatment of low risk tumours. British Medical Journal (2013). https://doi:10.1136/bmj.f4706\u003c/li\u003e\n\u003cli\u003eVaccarella S, Franceschi S, Bray F, Wild CP, Plummer M, Dal Maso L.: Worldwide Thyroid-Cancer Epidemic? The Increasing Impact of Overdiagnosis. New England Journal of Medicine (2016). https://doi:10.1056/nejmp1604412\u003c/li\u003e\n\u003cli\u003eHay ID, Hutchinson ME, Gonzalez-Losada T, et al.: Papillary thyroid microcarcinoma: A study of 900 cases observed in a 60-year period. Surgery (2008). https://doi:10.1016/j.surg.2008.08.035\u003c/li\u003e\n\u003cli\u003eMiyauchi A.: Clinical Trials of Active Surveillance of Papillary Microcarcinoma of the Thyroid. World Journal of Surgery (2016). https://doi:10.1007/s00268-015-3392-y\u003c/li\u003e\n\u003cli\u003eTuttle RM, Fagin JA, Minkowitz G, et al.: Natural History and Tumor Volume Kinetics of Papillary Thyroid Cancers During Active Surveillance. Journal of the American Medical Association Otolaryngology\u0026ndash;Head \u0026amp; Neck Surgery (2017). https://doi:10.1001/jamaoto.2017.1442\u003c/li\u003e\n\u003cli\u003eOda H, Miyauchi A, Ito Y, et al.: Comparison of the costs of active surveillance and immediate surgery in the management of low-risk papillary microcarcinoma of the thyroid. Endocrine Journal (2017). https://doi:10.1507/endocrj.ej16-0381\u003c/li\u003e\n\u003cli\u003eKong SH, Ryu J, Kim MJ, et al.: Longitudinal Assessment of Quality of Life According to Treatment Options in Low-Risk Papillary Thyroid Microcarcinoma Patients: Active Surveillance or Immediate Surgery (Interim Analysis of MAeSTro). Thyroid (2019). https://doi:10.1089/thy.2018.0624\u003c/li\u003e\n\u003cli\u003eWang TS, Goffredo P, Sosa JA, Roman SA.: Papillary Thyroid Microcarcinoma: An Over-Treated Malignancy? World Journal of Surgery (2014). https://doi:10.1007/s00268-014-2602-3\u003c/li\u003e\n\u003cli\u003eMoten AS, Zhao H, Willis AI.: The overuse of radioactive iodine in low-risk papillary thyroid cancer patients. Surgical Oncology (2019). https://doi:10.1016/j.suronc.2019.05.011\u003c/li\u003e\n\u003cli\u003eScheffel RS, Zanella AB, Dora JM, Maia AL.: Timing of Radioactive Iodine Administration Does Not Influence Outcomes in Patients with Differentiated Thyroid Carcinoma. Thyroid (2016). https://doi:10.1089/thy.2016.0038\u003c/li\u003e\n\u003cli\u003eNava CF, Scheffel RS, Zanella AB, Zelmanovitz F, Maia AL, Dora JM.: Reappraising the Diagnostic Accuracy of Post-Treatment Whole-Body Scans for Differentiated Thyroid Carcinoma. Hormone and Metabolic Research (2020). https://doi:10.1055/a-1212-8594\u003c/li\u003e\n\u003cli\u003eNava CF, Zanella AB, Scheffel RS, Maia AL, Dora JM.: Impact of the updated TNM staging criteria on prediction of persistent disease in a differentiated thyroid carcinoma cohort. Archives of Endocrinology and Metabolism (2019). https://doi:10.20945/2359-3997000000097\u003c/li\u003e\n\u003cli\u003eCooper DS, Doherty GM, Haugen BR, et al.: Revised American Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid (2009). https://doi:10.1089/thy.2009.0110\u003c/li\u003e\n\u003cli\u003eHaugen BR, Alexander EK, Bible KC, et al.: 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid (2016). https://doi:10.1089/thy.2015.0020\u003c/li\u003e\n\u003cli\u003eMomesso DP, Tuttle RM.: Update on Differentiated Thyroid Cancer Staging. Endocrinology and Metabolism Clinics of North America (2014). https://doi:10.1016/j.ecl.2014.02.010\u003c/li\u003e\n\u003cli\u003eTuttle RM, Tala H, Shah J, et al.: Estimating Risk of Recurrence in Differentiated Thyroid Cancer After Total Thyroidectomy and Radioactive Iodine Remnant Ablation: Using Response to Therapy Variables to Modify the Initial Risk Estimates Predicted by the New American Thyroid Association Staging System. Thyroid (2010). https://doi:10.1089/thy.2010.0178\u003c/li\u003e\n\u003cli\u003eVaisman F, Momesso D, Bulzico DA, et al.: Spontaneous remission in thyroid cancer patients after biochemical incomplete response to initial therapy. Clinical Endocrinology (2012). https://doi:10.1111/j.1365-2265.2012.04342.x\u003c/li\u003e\n\u003cli\u003eBrandi ML, Bilezikian JP, Shoback D, et al.: Management of Hypoparathyroidism: Summary Statement and Guidelines. The Journal of Clinical Endocrinology \u0026amp; Metabolism (2016). https://doi:10.1210/jc.2015-3907\u003c/li\u003e\n\u003cli\u003eRoti E, degli Uberti EC, Bondanelli M, Braverman LE.: Thyroid papillary microcarcinoma: a descriptive and meta-analysis study. European Journal of Endocrinology (2008). https://doi:10.1530/eje-07-0896\u003c/li\u003e\n\u003cli\u003eLiu LS, Liang J, Li JH, et al.: The incidence and risk factors for central lymph node metastasis in cN0 papillary thyroid microcarcinoma: a meta-analysis. European Archives of Oto-Rhino-Laryngology (2016). https://doi:10.1007/s00405-016-4302-0\u003c/li\u003e\n\u003cli\u003eZhang L, Wei W, Ji Q, et al.: Risk Factors for Neck Nodal Metastasis in Papillary Thyroid Microcarcinoma: A Study of 1066 Patients. The Journal of Clinical Endocrinology \u0026amp; Metabolism (2012). https://doi:10.1210/jc.2011-1546\u003c/li\u003e\n\u003cli\u003eIto Y, Miyauchi A, Kihara M, Higashiyama T, Kobayashi K, Miya A.: Patient Age Is Significantly Related to the Progression of Papillary Microcarcinoma of the Thyroid Under Observation. Thyroid (2014). https://doi:10.1089/thy.2013.0367\u003c/li\u003e\n\u003cli\u003eSugitani I.: Active surveillance of low-risk papillary thyroid microcarcinoma. Best Practice \u0026amp; Research Clinical Endocrinology \u0026amp; Metabolism (2022). https://doi:10.1016/j.beem.2022.101630\u003c/li\u003e\n\u003cli\u003eMehanna H, Al-maqbili T, Carter B, et al.: Differences in the Recurrence and Mortality Outcomes Rates of Incidental and Nonincidental Papillary Thyroid Microcarcinoma: A Systematic Review and Meta-Analysis of 21 329 Person-Years of Follow-up. The Journal of Clinical Endocrinology \u0026amp; Metabolism (2014). https://doi:10.1210/jc.2013-2118\u003c/li\u003e\n\u003cli\u003eDom\u0026iacute;nguez JM, Nilo F, Mart\u0026iacute;nez MT, et al. Papillary thyroid microcarcinoma: characteristics at presentation, and evaluation of clinical and histological features associated with a worse prognosis in a Latin American cohort. Archives of Endocrinology and Metabolism (2018). https://doi:10.20945/2359-3997000000013\u003c/li\u003e\n\u003cli\u003eLeboulleux S, Tuttle RM, Pacini F, Schlumberger M.: Papillary thyroid microcarcinoma: time to shift from surgery to active surveillance? The Lancet Diabetes \u0026amp; Endocrinology (2016). https://doi:10.1016/s2213-8587(16)30180-2\u003c/li\u003e\n\u003cli\u003eSawka AM, Ghai S, Yoannidis T, et al.: A Prospective Mixed-Methods Study of Decision-Making on Surgery or Active Surveillance for Low-Risk Papillary Thyroid Cancer. Thyroid (2020). https://doi:10.1089/thy.2019.0592\u003c/li\u003e\n\u003cli\u003eSasaki T, Miyauchi A, Ito Y, et al.: Marked Decrease Over Time in Conversion Surgery After Active Surveillance of Low-Risk Papillary Thyroid Microcarcinoma. Thyroid (2020). https://doi:10.1089/thy.2020.0319\u003c/li\u003e\n\u003cli\u003eOda H, Miyauchi A, Ito Y, et al.: Incidences of Unfavorable Events in the Management of Low-Risk Papillary Microcarcinoma of the Thyroid by Active Surveillance Versus Immediate Surgery. Thyroid (2016). https://doi:10.1089/thy.2015.0313\u003c/li\u003e\n\u003cli\u003eSmulever A, Pitoia F.: Active surveillance in papillary thyroid carcinoma: not easily accepted but possible in Latin America. Archives of Endocrinology and Metabolism (2019). https://doi:10.20945/2359-3997000000168\u003c/li\u003e\n\u003cli\u003eSosa JA.: Extent of Surgery for Papillary Thyroid Cancer Is Not Associated with Survival: An Analysis of 61,775 Patients. VideoEndocrinology (2014). https://doi:10.1089/ve.2014.0026\u003c/li\u003e\n\u003cli\u003eWelch HG, Doherty GM.: Saving Thyroids \u0026mdash; Overtreatment of Small Papillary Cancers. New England Journal of Medicine (2018). https://doi:10.1056/nejmp1804426\u003c/li\u003e\n\u003cli\u003eDurante C, Montesano T, Torlontano M, et al.: Papillary Thyroid Cancer: Time Course of Recurrences During Postsurgery Surveillance. The Journal of Clinical Endocrinology \u0026amp; Metabolism (2013). https://doi:10.1210/jc.2012-3401\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1.\u0026nbsp;\u003c/strong\u003eCharacteristics of the 257 patients with PTMC who underwent total thyroidectomy and 2 who underwent lobectomy.\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"58.48056537102474%\"\u003e\n \u003cp\u003eFemale sex \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"41.51943462897526%\"\u003e\n \u003cp\u003e216 (84.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"58.48056537102474%\"\u003e\n \u003cp\u003eAge at diagnosis (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"41.51943462897526%\"\u003e\n \u003cp\u003e48.3 \u0026plusmn; 13.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"58.48056537102474%\"\u003e\n \u003cp\u003eTumor size (cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"41.51943462897526%\"\u003e\n \u003cp\u003e0.68 \u0026plusmn; 0.26\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"58.48056537102474%\"\u003e\n \u003cp\u003eMulticentric \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"41.51943462897526%\"\u003e\n \u003cp\u003e78 (30.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" width=\"100%\"\u003e\n \u003cp\u003eLymph node metastasis \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"58.48056537102474%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; N0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"41.51943462897526%\"\u003e\n \u003cp\u003e153 (59.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"58.48056537102474%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; N1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"41.51943462897526%\"\u003e\n \u003cp\u003e63 (24.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"58.48056537102474%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Nx\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"41.51943462897526%\"\u003e\n \u003cp\u003e41 (16.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"58.48056537102474%\"\u003e\n \u003cp\u003eDistant metastasis \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"41.51943462897526%\"\u003e\n \u003cp\u003e1 (0.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" width=\"100%\"\u003e\n \u003cp\u003eTNM AJCC stage \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"58.48056537102474%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; I\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"41.51943462897526%\"\u003e\n \u003cp\u003e241 (93.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"58.48056537102474%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"41.51943462897526%\"\u003e\n \u003cp\u003e16 (6.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" width=\"100%\"\u003e\n \u003cp\u003eAmerican Thyroid Association\u0026nbsp;2009 Risk Stratification System \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"58.48056537102474%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Low\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"41.51943462897526%\"\u003e\n \u003cp\u003e170 (66.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"58.48056537102474%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Intermediate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"41.51943462897526%\"\u003e\n \u003cp\u003e86 (33.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"58.48056537102474%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; High\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"41.51943462897526%\"\u003e\n \u003cp\u003e1 (0.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"58.48056537102474%\"\u003e\n \u003cp\u003eRadioiodine \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"41.51943462897526%\"\u003e\n \u003cp\u003e156 (60.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"58.48056537102474%\"\u003e\n \u003cp\u003eRadioiodine Activity (mCi)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"41.51943462897526%\"\u003e\n \u003cp\u003e88.3 \u0026plusmn; 34.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" width=\"100%\"\u003e\n \u003cp\u003eAdverse Surgical Outcomes \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"58.48056537102474%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Permanent hypoparathyroidism\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"41.51943462897526%\"\u003e\n \u003cp\u003e20 (7.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"58.48056537102474%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Persistent subjective voice disturbance\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"41.51943462897526%\"\u003e\n \u003cp\u003e14 (5.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"58.48056537102474%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Any surgical complication\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"41.51943462897526%\"\u003e\n \u003cp\u003e31 (12.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" width=\"100%\"\u003e\n \u003cp\u003eDynamic response to therapy stratification after initial treatment\u0026nbsp;\u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"58.48056537102474%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Excellent response\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"41.51943462897526%\"\u003e\n \u003cp\u003e130 (58.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"58.48056537102474%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Indeterminate response\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"41.51943462897526%\"\u003e\n \u003cp\u003e74 (33.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"58.48056537102474%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Biochemical incomplete response\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"41.51943462897526%\"\u003e\n \u003cp\u003e10 (4.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"58.48056537102474%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Cervical structural incomplete response\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"41.51943462897526%\"\u003e\n \u003cp\u003e9 (4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"58.48056537102474%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Distant structural incomplete response\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"41.51943462897526%\"\u003e\n \u003cp\u003e1 (0.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" width=\"100%\"\u003e\n \u003cp\u003eDynamic response to therapy stratification\u0026nbsp;at last follow-up\u0026nbsp;\u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"58.48056537102474%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Excellent response\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"41.51943462897526%\"\u003e\n \u003cp\u003e147 (63.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"58.48056537102474%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Indeterminate response\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"41.51943462897526%\"\u003e\n \u003cp\u003e66 (28.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"58.48056537102474%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Biochemical incomplete response\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"41.51943462897526%\"\u003e\n \u003cp\u003e11 (4.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"58.48056537102474%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Cervical structural incomplete response\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"41.51943462897526%\"\u003e\n \u003cp\u003e8 (3.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"58.48056537102474%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Distant structural incomplete response\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"41.51943462897526%\"\u003e\n \u003cp\u003e1 (0.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"58.48056537102474%\"\u003e\n \u003cp\u003eFollow-up (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"41.51943462897526%\"\u003e\n \u003cp\u003e5.5 (2.5-9.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eData are shown as number (%), mean \u0026plusmn; SD and median (P25-P75).\u003c/p\u003e\n\u003cp\u003eN0: No evidence of lymph node metastasis; N1: metastasis to lymph nodes; Nx: regional lymph nodes not accessed.\u003c/p\u003e\n\u003cp\u003eTNM/AJCC: TNM staging system of the American Joint Committee on Cancer.\u003c/p\u003e\n\u003cp\u003eATA: American Thyroid Association.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2.\u0026nbsp;\u003c/strong\u003eCharacteristics of 207* patients with PTMC who underwent total thyroidectomy and 2 who underwent lobectomy compared by modality of diagnosis.\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45.6049%;\" valign=\"bottom\" width=\"45.6910569105691%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.3655%;\" valign=\"bottom\" width=\"20.32520325203252%\"\u003e\n \u003cp\u003e\u003cstrong\u003eIncidental diagnosis\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=92)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.584%;\" valign=\"top\" width=\"21.463414634146343%\"\u003e\n \u003cp\u003e\u003cstrong\u003eNonincidental\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=115)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3586%;\" valign=\"top\" width=\"12.357723577235772%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eP-\u003c/strong\u003e\u003cstrong\u003evalue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45.6049%;\" valign=\"bottom\" width=\"45.6910569105691%\"\u003e\n \u003cp\u003eFemale \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.3655%;\" valign=\"bottom\" width=\"20.32520325203252%\"\u003e\n \u003cp\u003e81 (88.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.584%;\" valign=\"bottom\" width=\"21.463414634146343%\"\u003e\n \u003cp\u003e93 (80.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3586%;\" valign=\"bottom\" width=\"12.357723577235772%\"\u003e\n \u003cp\u003e0.161\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45.6049%;\" valign=\"bottom\" width=\"45.6910569105691%\"\u003e\n \u003cp\u003eAge at diagnosis (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.3655%;\" valign=\"bottom\" width=\"20.32520325203252%\"\u003e\n \u003cp\u003e50.4 \u0026plusmn; 12.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.584%;\" valign=\"bottom\" width=\"21.463414634146343%\"\u003e\n \u003cp\u003e49.3 \u0026plusmn; 14.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3586%;\" valign=\"bottom\" width=\"12.357723577235772%\"\u003e\n \u003cp\u003e0.570\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45.6049%;\" valign=\"bottom\" width=\"45.6910569105691%\"\u003e\n \u003cp\u003eTumor size (cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.3655%;\" valign=\"bottom\" width=\"20.32520325203252%\"\u003e\n \u003cp\u003e0.60 \u0026plusmn; 0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.584%;\" valign=\"bottom\" width=\"21.463414634146343%\"\u003e\n \u003cp\u003e0.72 \u0026plusmn; 0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3586%;\" valign=\"bottom\" width=\"12.357723577235772%\"\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45.6049%;\" valign=\"bottom\" width=\"45.6910569105691%\"\u003e\n \u003cp\u003eMulticentric \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.3655%;\" valign=\"bottom\" width=\"20.32520325203252%\"\u003e\n \u003cp\u003e26 (28.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.584%;\" valign=\"bottom\" width=\"21.463414634146343%\"\u003e\n \u003cp\u003e33 (28.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3586%;\" valign=\"bottom\" width=\"12.357723577235772%\"\u003e\n \u003cp\u003e0.914\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45.6049%;\" valign=\"bottom\" width=\"45.6910569105691%\"\u003e\n \u003cp\u003eLymph node metastasis \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.3655%;\" valign=\"bottom\" width=\"20.32520325203252%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.584%;\" valign=\"bottom\" width=\"21.463414634146343%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3586%;\" valign=\"bottom\" width=\"12.357723577235772%\"\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: 45.6049%;\" valign=\"bottom\" width=\"45.6910569105691%\"\u003e\n \u003cp\u003e\u0026nbsp;\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;N0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.3655%;\" valign=\"bottom\" width=\"20.32520325203252%\"\u003e\n \u003cp\u003e68 (73.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.584%;\" valign=\"bottom\" width=\"21.463414634146343%\"\u003e\n \u003cp\u003e65 (57.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3586%;\" valign=\"bottom\" width=\"12.357723577235772%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45.6049%;\" valign=\"bottom\" width=\"45.6910569105691%\"\u003e\n \u003cp\u003e\u0026nbsp;\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;N1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.3655%;\" valign=\"bottom\" width=\"20.32520325203252%\"\u003e\n \u003cp\u003e11 (11.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.584%;\" valign=\"bottom\" width=\"21.463414634146343%\"\u003e\n \u003cp\u003e36 (31.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3586%;\" valign=\"bottom\" width=\"12.357723577235772%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45.6049%;\" valign=\"bottom\" width=\"45.6910569105691%\"\u003e\n \u003cp\u003e\u0026nbsp;\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Nx\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.3655%;\" valign=\"bottom\" width=\"20.32520325203252%\"\u003e\n \u003cp\u003e13 (14.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.584%;\" valign=\"bottom\" width=\"21.463414634146343%\"\u003e\n \u003cp\u003e14 (12.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3586%;\" valign=\"bottom\" width=\"12.357723577235772%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45.6049%;\" valign=\"bottom\" width=\"45.6910569105691%\"\u003e\n \u003cp\u003eDistant metastasis \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.3655%;\" valign=\"bottom\" width=\"20.32520325203252%\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.584%;\" valign=\"bottom\" width=\"21.463414634146343%\"\u003e\n \u003cp\u003e1 (0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3586%;\" valign=\"bottom\" width=\"12.357723577235772%\"\u003e\n \u003cp\u003e0.370\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45.6049%;\" valign=\"bottom\" width=\"45.6910569105691%\"\u003e\n \u003cp\u003eTNM AJCC stage \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.3655%;\" valign=\"bottom\" width=\"20.32520325203252%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.584%;\" valign=\"bottom\" width=\"21.463414634146343%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3586%;\" valign=\"bottom\" width=\"12.357723577235772%\"\u003e\n \u003cp\u003e0.009\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45.6049%;\" valign=\"bottom\" width=\"45.6910569105691%\"\u003e\n \u003cp\u003e\u0026nbsp;\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;I\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.3655%;\" valign=\"bottom\" width=\"20.32520325203252%\"\u003e\n \u003cp\u003e91 (98.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.584%;\" valign=\"bottom\" width=\"21.463414634146343%\"\u003e\n \u003cp\u003e104 (90.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3586%;\" valign=\"bottom\" width=\"12.357723577235772%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45.6049%;\" valign=\"bottom\" width=\"45.6910569105691%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.3655%;\" valign=\"bottom\" width=\"20.32520325203252%\"\u003e\n \u003cp\u003e1 (1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.584%;\" valign=\"bottom\" width=\"21.463414634146343%\"\u003e\n \u003cp\u003e11 (9.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3586%;\" valign=\"bottom\" width=\"12.357723577235772%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45.6049%;\" valign=\"bottom\" width=\"45.6910569105691%\"\u003e\n \u003cp\u003eAmerican Thyroid Association\u0026nbsp;2009 Risk Stratification System \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.3655%;\" valign=\"bottom\" width=\"20.32520325203252%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.584%;\" valign=\"bottom\" width=\"21.463414634146343%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3586%;\" valign=\"bottom\" width=\"12.357723577235772%\"\u003e\n \u003cp\u003e0.135\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45.6049%;\" valign=\"bottom\" width=\"45.6910569105691%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Low\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.3655%;\" valign=\"bottom\" width=\"20.32520325203252%\"\u003e\n \u003cp\u003e69 (75.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.584%;\" valign=\"bottom\" width=\"21.463414634146343%\"\u003e\n \u003cp\u003e73 (63.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3586%;\" valign=\"bottom\" width=\"12.357723577235772%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45.6049%;\" valign=\"bottom\" width=\"45.6910569105691%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Intermediate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.3655%;\" valign=\"bottom\" width=\"20.32520325203252%\"\u003e\n \u003cp\u003e23 (25.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.584%;\" valign=\"bottom\" width=\"21.463414634146343%\"\u003e\n \u003cp\u003e41 (35.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3586%;\" valign=\"bottom\" width=\"12.357723577235772%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45.6049%;\" valign=\"bottom\" width=\"45.6910569105691%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; High\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.3655%;\" valign=\"bottom\" width=\"20.32520325203252%\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.584%;\" valign=\"bottom\" width=\"21.463414634146343%\"\u003e\n \u003cp\u003e1 (0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3586%;\" valign=\"bottom\" width=\"12.357723577235772%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45.6049%;\" valign=\"bottom\" width=\"45.6910569105691%\"\u003e\n \u003cp\u003eRadioiodine \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.3655%;\" valign=\"bottom\" width=\"20.32520325203252%\"\u003e\n \u003cp\u003e49 (55.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.584%;\" valign=\"bottom\" width=\"21.463414634146343%\"\u003e\n \u003cp\u003e66 (58.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3586%;\" valign=\"bottom\" width=\"12.357723577235772%\"\u003e\n \u003cp\u003e0.685\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45.6049%;\" valign=\"bottom\" width=\"45.6910569105691%\"\u003e\n \u003cp\u003eRadioiodine activity (mCi)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.3655%;\" valign=\"bottom\" width=\"20.32520325203252%\"\u003e\n \u003cp\u003e82.2 \u0026plusmn; 32.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.584%;\" valign=\"bottom\" width=\"21.463414634146343%\"\u003e\n \u003cp\u003e91.8 \u0026plusmn; 33.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3586%;\" valign=\"bottom\" width=\"12.357723577235772%\"\u003e\n \u003cp\u003e0.144\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45.6049%;\" valign=\"bottom\" width=\"45.6910569105691%\"\u003e\n \u003cp\u003eAdverse Surgical Outcomes \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.3655%;\" valign=\"bottom\" width=\"20.32520325203252%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.584%;\" valign=\"bottom\" width=\"21.463414634146343%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3586%;\" valign=\"bottom\" width=\"12.357723577235772%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45.6049%;\" valign=\"bottom\" width=\"45.6910569105691%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Permanent hypoparathyroidism\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.3655%;\" valign=\"top\" width=\"20.32520325203252%\"\u003e\n \u003cp\u003e3 (3.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.584%;\" valign=\"top\" width=\"21.463414634146343%\"\u003e\n \u003cp\u003e9 (7.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.403%;\" valign=\"top\" width=\"12.520325203252032%\"\u003e\n \u003cp\u003e0.164\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45.6049%;\" valign=\"bottom\" width=\"45.6910569105691%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Persistent subjective voice disturbance\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.3655%;\" valign=\"top\" width=\"20.32520325203252%\"\u003e\n \u003cp\u003e3 (3.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.584%;\" valign=\"top\" width=\"21.463414634146343%\"\u003e\n \u003cp\u003e7 (6.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.403%;\" valign=\"top\" width=\"12.520325203252032%\"\u003e\n \u003cp\u003e0.344\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45.6049%;\" valign=\"bottom\" width=\"45.6910569105691%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Any surgical complication\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.3655%;\" valign=\"top\" width=\"20.32520325203252%\"\u003e\n \u003cp\u003e5 (5.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.584%;\" valign=\"top\" width=\"21.463414634146343%\"\u003e\n \u003cp\u003e15 (13.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.403%;\" valign=\"top\" width=\"12.520325203252032%\"\u003e\n \u003cp\u003e0.064\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45.6049%;\" valign=\"bottom\" width=\"45.6910569105691%\"\u003e\n \u003cp\u003eDynamic response to therapy stratification after initial treatment\u0026nbsp;\u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.3655%;\" valign=\"bottom\" width=\"20.32520325203252%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.584%;\" valign=\"bottom\" width=\"21.463414634146343%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3586%;\" valign=\"bottom\" width=\"12.357723577235772%\"\u003e\n \u003cp\u003e0.811\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45.6049%;\" valign=\"bottom\" width=\"45.6910569105691%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Excellent response\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.3655%;\" valign=\"bottom\" width=\"20.32520325203252%\"\u003e\n \u003cp\u003e44 (55.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.584%;\" valign=\"bottom\" width=\"21.463414634146343%\"\u003e\n \u003cp\u003e57 (55.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3586%;\" valign=\"bottom\" width=\"12.357723577235772%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45.6049%;\" valign=\"bottom\" width=\"45.6910569105691%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Indeterminate response\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.3655%;\" valign=\"bottom\" width=\"20.32520325203252%\"\u003e\n \u003cp\u003e30 (37.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.584%;\" valign=\"bottom\" width=\"21.463414634146343%\"\u003e\n \u003cp\u003e35 (34.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3586%;\" valign=\"bottom\" width=\"12.357723577235772%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45.6049%;\" valign=\"bottom\" width=\"45.6910569105691%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Biochemical incomplete response\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.3655%;\" valign=\"bottom\" width=\"20.32520325203252%\"\u003e\n \u003cp\u003e4 (5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.584%;\" valign=\"bottom\" width=\"21.463414634146343%\"\u003e\n \u003cp\u003e5 (4.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3586%;\" valign=\"bottom\" width=\"12.357723577235772%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45.6049%;\" valign=\"bottom\" width=\"45.6910569105691%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Cervical structural incomplete response\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.3655%;\" valign=\"bottom\" width=\"20.32520325203252%\"\u003e\n \u003cp\u003e2 (2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.584%;\" valign=\"bottom\" width=\"21.463414634146343%\"\u003e\n \u003cp\u003e5 (4.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3586%;\" valign=\"bottom\" width=\"12.357723577235772%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45.6049%;\" valign=\"bottom\" width=\"45.6910569105691%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Distant structural incomplete response\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.3655%;\" valign=\"bottom\" width=\"20.32520325203252%\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.584%;\" valign=\"bottom\" width=\"21.463414634146343%\"\u003e\n \u003cp\u003e1 (1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3586%;\" valign=\"bottom\" width=\"12.357723577235772%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45.6049%;\" valign=\"bottom\" width=\"45.6910569105691%\"\u003e\n \u003cp\u003eDynamic response to therapy\u0026nbsp;stratification at last follow-up\u0026nbsp;- n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.3655%;\" valign=\"bottom\" width=\"20.32520325203252%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.584%;\" valign=\"bottom\" width=\"21.463414634146343%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3586%;\" valign=\"bottom\" width=\"12.357723577235772%\"\u003e\n \u003cp\u003e0.827\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45.6049%;\" valign=\"bottom\" width=\"45.6910569105691%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Excellent response\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.3655%;\" valign=\"bottom\" width=\"20.32520325203252%\"\u003e\n \u003cp\u003e49 (59.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.584%;\" valign=\"bottom\" width=\"21.463414634146343%\"\u003e\n \u003cp\u003e66 (63.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3586%;\" valign=\"bottom\" width=\"12.357723577235772%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45.6049%;\" valign=\"bottom\" width=\"45.6910569105691%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Indeterminate response\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.3655%;\" valign=\"bottom\" width=\"20.32520325203252%\"\u003e\n \u003cp\u003e25 (30.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.584%;\" valign=\"bottom\" width=\"21.463414634146343%\"\u003e\n \u003cp\u003e30 (28.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3586%;\" valign=\"bottom\" width=\"12.357723577235772%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45.6049%;\" valign=\"bottom\" width=\"45.6910569105691%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Biochemical incomplete response\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.3655%;\" valign=\"bottom\" width=\"20.32520325203252%\"\u003e\n \u003cp\u003e5 (6.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.584%;\" valign=\"bottom\" width=\"21.463414634146343%\"\u003e\n \u003cp\u003e4 (3.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3586%;\" valign=\"bottom\" width=\"12.357723577235772%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45.6049%;\" valign=\"bottom\" width=\"45.6910569105691%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Cervical structural incomplete response\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.3655%;\" valign=\"bottom\" width=\"20.32520325203252%\"\u003e\n \u003cp\u003e3 (3.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.584%;\" valign=\"bottom\" width=\"21.463414634146343%\"\u003e\n \u003cp\u003e3 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3586%;\" valign=\"bottom\" width=\"12.357723577235772%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45.6049%;\" valign=\"bottom\" width=\"45.6910569105691%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Distant structural incomplete response\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.3655%;\" valign=\"bottom\" width=\"20.32520325203252%\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.584%;\" valign=\"bottom\" width=\"21.463414634146343%\"\u003e\n \u003cp\u003e1 (1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3586%;\" valign=\"bottom\" width=\"12.357723577235772%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 45.6049%;\" valign=\"bottom\" width=\"45.6910569105691%\"\u003e\n \u003cp\u003eFollow-up (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.3655%;\" valign=\"bottom\" width=\"20.32520325203252%\"\u003e\n \u003cp\u003e5.2 (1.8-8.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.584%;\" valign=\"bottom\" width=\"21.463414634146343%\"\u003e\n \u003cp\u003e5.0 (2.5-7.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3586%;\" valign=\"bottom\" width=\"12.357723577235772%\"\u003e\n \u003cp\u003e0.490\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e* We could not classify 50 patients as incidental or nonincidental diagnosis. Data are shown as number (%), mean \u0026plusmn; SD and median (P25-P75).\u003c/p\u003e\n\u003cp\u003eN0: No evidence of lymph node metastasis; N1: metastasis to lymph nodes; Nx: regional lymph nodes not accessed.\u003c/p\u003e\n\u003cp\u003eTNM/AJCC: TNM staging system of the American Joint Committee on Cancer.\u003c/p\u003e\n\u003cp\u003eATA: American Thyroid Association.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3.\u003c/strong\u003e Univariate analysis of predictors of persistent disease.\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.8301043219076%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"50.67064083457526%\"\u003e\n \u003cp\u003e\u003cstrong\u003eDisease Status\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.49925484351714%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.779761904761905%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.785714285714285%\"\u003e\n \u003cp\u003e\u003cstrong\u003eExcellent/Indeterminate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=213)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.958333333333332%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePersistent disease\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=20)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.476190476190476%\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.779761904761905%\"\u003e\n \u003cp\u003eMale\u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.785714285714285%\"\u003e\n \u003cp\u003e28 (13.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.958333333333332%\"\u003e\n \u003cp\u003e6 (30.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.476190476190476%\"\u003e\n \u003cp\u003e0.041\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.779761904761905%\"\u003e\n \u003cp\u003eAge at diagnosis (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.785714285714285%\"\u003e\n \u003cp\u003e49.1\u0026nbsp;\u0026plusmn;\u0026nbsp;12.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.958333333333332%\"\u003e\n \u003cp\u003e42.6\u0026nbsp;\u0026plusmn;\u0026nbsp;14.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.476190476190476%\"\u003e\n \u003cp\u003e0.110\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.779761904761905%\"\u003e\n \u003cp\u003eTumor size (cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.785714285714285%\"\u003e\n \u003cp\u003e0.69\u0026nbsp;\u0026plusmn;\u0026nbsp;0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.958333333333332%\"\u003e\n \u003cp\u003e0.60\u0026nbsp;\u0026plusmn;\u0026nbsp;0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.476190476190476%\"\u003e\n \u003cp\u003e0.659\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.779761904761905%\"\u003e\n \u003cp\u003eMulticentricity \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.785714285714285%\"\u003e\n \u003cp\u003e61 (28.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.958333333333332%\"\u003e\n \u003cp\u003e9 (45.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.476190476190476%\"\u003e\n \u003cp\u003e0.135\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.779761904761905%\"\u003e\n \u003cp\u003eNodal metastasis \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.785714285714285%\"\u003e\n \u003cp\u003e44 (20.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.958333333333332%\"\u003e\n \u003cp\u003e12 (60.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.476190476190476%\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" width=\"84.50074515648286%\"\u003e\n \u003cp\u003eTNM AJCC stage \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.49925484351714%\"\u003e\n \u003cp\u003e0.133\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.779761904761905%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; I\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.785714285714285%\"\u003e\n \u003cp\u003e200 (93.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.958333333333332%\"\u003e\n \u003cp\u003e17 (85.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.476190476190476%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.779761904761905%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.785714285714285%\"\u003e\n \u003cp\u003e13 (6.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.958333333333332%\"\u003e\n \u003cp\u003e3 (15.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.476190476190476%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" width=\"84.50074515648286%\"\u003e\n \u003cp\u003eAmerican Thyroid Association\u0026nbsp;Risk Stratification System 2009 \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.49925484351714%\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.779761904761905%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Low\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.785714285714285%\"\u003e\n \u003cp\u003e151 (70.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.958333333333332%\"\u003e\n \u003cp\u003e5 (25.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.476190476190476%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.779761904761905%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Intermediate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.785714285714285%\"\u003e\n \u003cp\u003e62 (29.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.958333333333332%\"\u003e\n \u003cp\u003e14 (70.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.476190476190476%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.779761904761905%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; High\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.785714285714285%\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.958333333333332%\"\u003e\n \u003cp\u003e1 (5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.476190476190476%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.779761904761905%\"\u003e\n \u003cp\u003eRadioiodine use \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.785714285714285%\"\u003e\n \u003cp\u003e132 (62.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.958333333333332%\"\u003e\n \u003cp\u003e13 (65.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.476190476190476%\"\u003e\n \u003cp\u003e0.388\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.779761904761905%\"\u003e\n \u003cp\u003eRadioiodine activity (mCi)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.785714285714285%\"\u003e\n \u003cp\u003e86.9\u0026nbsp;\u0026plusmn;\u0026nbsp;34.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.958333333333332%\"\u003e\n \u003cp\u003e89.8\u0026nbsp;\u0026plusmn;\u0026nbsp;39.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.476190476190476%\"\u003e\n \u003cp\u003e0.775\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" width=\"84.50074515648286%\"\u003e\n \u003cp\u003eDynamic response to therapy\u0026nbsp;after initial treatment \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.49925484351714%\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.779761904761905%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Excellent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.785714285714285%\"\u003e\n \u003cp\u003e128 (60.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.958333333333332%\"\u003e\n \u003cp\u003e2 (10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.476190476190476%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.779761904761905%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Indeterminate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.785714285714285%\"\u003e\n \u003cp\u003e72 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.958333333333332%\"\u003e\n \u003cp\u003e3 (15.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.476190476190476%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.779761904761905%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Biochemical incomplete response\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.785714285714285%\"\u003e\n \u003cp\u003e4 (1.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.958333333333332%\"\u003e\n \u003cp\u003e6 (30.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.476190476190476%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.779761904761905%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Cervical structural incomplete response\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.785714285714285%\"\u003e\n \u003cp\u003e3 (1.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.958333333333332%\"\u003e\n \u003cp\u003e6 (30.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.476190476190476%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.779761904761905%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Distant structural incomplete response\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.785714285714285%\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.958333333333332%\"\u003e\n \u003cp\u003e1 (5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.476190476190476%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.779761904761905%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Unknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.785714285714285%\"\u003e\n \u003cp\u003e7 (3.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.958333333333332%\"\u003e\n \u003cp\u003e2 (10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.476190476190476%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.779761904761905%\"\u003e\n \u003cp\u003eNonincidental diagnosis \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.785714285714285%\"\u003e\n \u003cp\u003e96 (45.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.958333333333332%\"\u003e\n \u003cp\u003e8 (40.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.476190476190476%\"\u003e\n \u003cp\u003e0.883\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eData are shown as number (%), mean \u0026plusmn; SD and median (P25-P75)\u003c/p\u003e\n\u003cp\u003eTNM/AJCC: TNM staging system of the American Joint Committee on Cancer.\u003c/p\u003e\n\u003cp\u003eATA: American Thyroid Association.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4.\u0026nbsp;\u003c/strong\u003eMultivariate analysis of predictors of lymph node metastasis and persistent disease.\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRR [95%CI]\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePredictors of lymph node metastasis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Male sex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.30 [1.51 \u0026ndash; 3.52]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Age at diagnosis (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.97 [0.96\u0026nbsp;\u0026ndash;\u0026nbsp;0.99]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Tumor size\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.60 [0.93 \u0026ndash; 1.14]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.599\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Multicentricity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.00 [0.62\u0026nbsp;\u0026ndash;\u0026nbsp;1.62]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.970\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Nonincidental diagnosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.17 [1.20\u0026nbsp;\u0026ndash;\u0026nbsp;3.92]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.010\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePredictors of persistent disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Male sex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.75 [0.59 \u0026ndash; 5.15]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.304\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Age at diagnosis (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.95 [0.90 \u0026ndash; 1.01]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.089\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Tumor size\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.82 [0.64 \u0026ndash; 1.06]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.135\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Multicentricity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.42 [1.04 \u0026ndash; 5.60]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.039\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Nodal metastasis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4.48 [1.60 \u0026ndash; 12.30]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Nonincidental diagnosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.19 [0.91 \u0026ndash; 5.26]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.078\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eRR: relative risk.\u003c/p\u003e\n\u003cp\u003eCI: confidence interval.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5.\u0026nbsp;\u003c/strong\u003eUnivariate analysis of predictors of lymph node metastasis.\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNodal metastasis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbsent\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=153)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDetected\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=63)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMale\u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e13 (8.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e24 (38.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAge at diagnosis (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e50.6\u0026nbsp;\u0026plusmn;\u0026nbsp;12.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e41.1\u0026nbsp;\u0026plusmn;\u0026nbsp;12.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eTumor size (cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.68\u0026nbsp;\u0026plusmn;\u0026nbsp;0.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.73\u0026nbsp;\u0026plusmn;\u0026nbsp;0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;0.235\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMulticentric \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e44 (28.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e27 (42.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;0.048\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003eType of diagnosis \u0026ndash; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNonincidental\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e65 (42.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e36 (57.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIncidental\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e68 (44.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e11 (17.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNot categorized\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e20 (13.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e16 (25.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eData are shown as number (%), mean \u0026plusmn; SD and median (P25-P75).\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Papillary thyroid carcinoma, Papillary thyroid microcarcinoma, Treatment, Prognosis","lastPublishedDoi":"10.21203/rs.3.rs-1880064/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1880064/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose: \u003c/strong\u003eActive surveillance (AS) has been gaining attention as an option for papillary thyroid microcarcinoma (PTMC) management in selected patients. However, some questions remain on PTMC behavior, particularly on tumor multicentricity and cervical metastases. Our aim is to gather insights on the natural history of PTMC on patients treated with thyroidectomy.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eConsecutive patients diagnosed with PTMC (tumor size ≤ 1.0 cm) had their clinical characteristics, interventions, and outcomes described. Patients were classified as incidental or nonincidental based on the diagnosis of PTMC after or before surgery, respectively. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e A cohort of 257 patients was included for this study, 84.0% of which were women, and the mean age was of 48.3 ± 13.5 years. The mean tumor size was of 0.68 ± 0.26 cm, 30.4% were multifocal, 24.5% had cervical metastasis, and 0.4% distant metastasis. The nonincidental and incidental tumors differed in tumor size (0.72 ± 0.24 and 0.60 ± 0.28 cm, respectively, p=0.003) and in presence of cervical metastasis (31.3% and 11.9%, respectively, p\u0026lt;0.001). Male sex, nonincidental diagnosis, and younger age were independent predictors of cervical metastasis. Notably, each year less in age represented an increase of 3% in likelihood of nodal metastasis (p\u0026lt;0.001). After 5.5 years (P25-75 2.5-9.7) of follow-up, only 3.8% of patients had persistent structural disease (3.4% cervical). Predictors of persistent disease at multivariate analysis included cervical metastasis and multicentricity.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e Incidental and nonincidental PTMC patients displayed excellent outcomes.\u003cstrong\u003e \u003c/strong\u003eCervical metastasis and multicentricity are frequent findings in PTMC and prognostic factors for persistent disease.\u0026nbsp;\u003c/p\u003e","manuscriptTitle":"Papillary thyroid microcarcinoma: insights from a cohort of 257 thyroidectomized patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-08-01 16:58:27","doi":"10.21203/rs.3.rs-1880064/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5ba42df4-f9c5-401d-b4df-8d8e8e5a0e30","owner":[],"postedDate":"August 1st, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-08-28T21:12:31+00:00","versionOfRecord":[],"versionCreatedAt":"2022-08-01 16:58:27","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1880064","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1880064","identity":"rs-1880064","version":["v1"]},"buildId":"WrCJVZZCHTDjtuVLN7oU0","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}