Low-risk Papillary Thyroid Cancer Research Articles

Adherence to ATA 2015 guidelines in the management of unifocal non-invasive papillary thyroid cancer: a clinical survey among endocrinologists and surgeons.

Despite updated guidelines, management of thyroid nodules remains controversial. We aim to check implementation of new guidelines by ear-nose-throat (ENT) surgeons and endocrinologists. A questionnaire was e-mailed including demographic data and an index case: a healthy 26-year-old women with a 3-cm Bethesda III (B3) atypia of undetermined significance solitary nodule and eventually papillary thyroid cancer (PTC). Respondent rate was 50.5%, 93 endocrinologists, 55 surgeons. For this case, 77.4% would repeat fine-needle aspiration (FNA), 25.3% order molecular analysis and 22.6% do surgery. If repeated FNA remained B3, 51% would choose surgery, 17.3% molecular analysis and 31.6% follow-up only. If repeated FNA was B6, 58.5% would recommend total (TTx) and 41.5% hemithyroidectomy (HTx). In pathologically confirmed PTC after HTx, 42.4% would recommend completion, 26.8% radioactive iodine (RAI) treatment. For a > = 4-cm tumor, 49.2% would recommend TTx. For a tumor 2-4cm, 41% would recommend TTx. Variables favoring TTx were family history and radiation exposure. Only 17.4% would prefer TTx when small benign contralateral tumor is present. Reassessment at 1year with undetectable thyroglobulin (Tg) included stimulated Tg (stTg) (72.5%), neck US only (27.5%) and combined US-stTg (59.4%); only 10.3% would order a diagnostic scan. For recurrence in two (13-9mm) lymph nodes, 59.3% recommend reoperation, 16.3% RAI and 24.4% active surveillance. There were no major differences between endocrinologists and ENT surgeons. We report a considerable lack of adherence to new guidelines, with only 50% recommending HTx for a 4-cm unifocal low-risk PTC tumor.

Changes in Serum Thyroglobulin Levels After Lobectomy in Patients with Low-Risk Papillary Thyroid Cancer.

Low-risk patients with differentiated thyroid cancer can be treated with thyroid lobectomy. Serial measurements of serum thyroglobulin (Tg) are recommended for surveillance, but the cutoff values indicating recurrence are not known. This study documented the natural course of serum Tg levels during follow-up after lobectomy for low-risk papillary thyroid carcinoma (PTC) and evaluated whether changes in serum Tg levels predict disease recurrence. This historical cohort study included 208 patients with low-risk PTC who underwent lobectomy but did not require hormone replacement. Postoperative serum Tg levels and Tg/thyrotropin (TSH) ratios and neck ultrasound were evaluated during a follow-up period with a median of 6.9 years. The serum Tg levels increased gradually, and the proportion of patients with levels >10 ng/dL increased annually by 13.9%, 18.8%, 22.1%, 21.9%, 28.4%, and 28.9% during the six-year follow-up period (β = 0.574, p = 0.027). The relative serum Tg levels increased by 10% annually (β = 0.105, p < 0.001), and the levels of Tg and Tg/TSH ratios in 19 patients with recurrent disease did not differ significantly (β = 0.150, p = 0.090). Patients without recurrent disease were more likely to have serum Tg levels increased by >20% (p = 0.022). There were no significant differences in the proportions of patients with serum Tg levels increased by ≥50% or ≥100% in terms of the disease recurrence. Serum Tg levels and the Tg/TSH ratio increased gradually after lobectomy in patients with and without recurrences, without any significant differences. Periodic measurements of serum Tg levels seem to have limited value in predicting recurrent PTCs after lobectomy.

Evaluation of the Role of BRAFV600E Somatic Mutation on Papillary Thyroid Cancer Disease Persistence: A Prospective Study

Background: BRAFV600E (c.1799T>A) somatic mutation evaluation in fine needle aspiration biopsies (FNAB) is a powerful diagnostic tool in the settings of papillary thyroid cancer (PTC). However, its prognostic value is still a matter of great debate and has been addressed mostly in retrospective studies. Objectives: To evaluate whether the somatic BRAFV600E mutation, assessed by direct sequencing in FNAB material of thyroid nodules, may correlate with disease persistence in PTC patients. Study Design: We conducted a prospective cohort study investigating 160 PTC patients previously assessed for the somatic BRAFV600E mutation, and submitted to total thyroidectomy, with a follow-up of 2–10 years. Patients were matched according to somatic BRAFV600E mutation (80 BRAF+ and 80 BRAF– patients) and to the presence (LN+, 40 patients each group) or absence (LN, 40 patients each group) of neck lymphnode metastases. Disease persistence was considered according to basal or TSH-stimulated Thyroglobulin (TG) levels, anti-TG antibodies, neck ultrasound, CT scan where applicable and whole body scan after radioiodine ablation treatment (RAI). Results: The presence of the somatic BRAFV600E mutation did not influence the indication for RAI. None of the enrolled patients showed disease recurrence or died due to disease-related causes. During follow-up, disease persistence did not correlate with the presence of somatic BRAFV600E mutation both in patients submitted to RAI nor in those treated more conservatively. Conclusions: The somatic BRAFV600E mutation does not associate with a worse prognosis in low risk PTC and, in our settings, may not be considered an independent risk factor for disease persistence.

Thyroglobulin Levels Do Not Predict Recurrence After Lobectomy for Low-Risk Papillary Thyroid Cancer

Clinical ThyroidologyVol. 30, No. 7 SummariesThyroglobulin Levels Do Not Predict Recurrence After Lobectomy for Low-Risk Papillary Thyroid CancerMasha J. Livhits and Michael W. YehMasha J. LivhitsSearch for more papers by this author and Michael W. YehSearch for more papers by this authorPublished Online:1 Jul 2018https://doi.org/10.1089/ct.2018;30.312-314AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetails Volume 30Issue 7Jul 2018 InformationCopyright 2018 American Thyroid Association, Inc.To cite this article:Masha J. Livhits and Michael W. Yeh.Thyroglobulin Levels Do Not Predict Recurrence After Lobectomy for Low-Risk Papillary Thyroid Cancer.Clinical Thyroidology.Jul 2018.312-314.http://doi.org/10.1089/ct.2018;30.312-314Published in Volume: 30 Issue 7: July 1, 2018PDF download

Impact of Extent of Surgery on Tumor Recurrence and Survival for Papillary Thyroid Cancer Patients.

The extent of surgery for low-risk papillary thyroid cancer (PTC) has been the subject of debate among experts for decades. In this paper, we aimed to systematically review whether thyroid lobectomy versus total thyroidectomy for PTC patients with tumors measuring 1.0-4.0cm impacts tumor recurrence and survival. A systematic review of the literature from January 1990 to February 2018 yielded 13 relevant studies, including eight national cancer registry database studies, one multi-institutional thyroid cancer-specific database, three large-scale institutional series, and one meta-analysis. Data from these studies demonstrate that total thyroidectomy for the treatment of PTC measuring 1.0-4.0cm does not confer a clinically significant improvement in disease-specific survival compared with thyroid lobectomy. Four of six studies also reported that total thyroidectomy is associated with a small but statistically significant improvement in disease-free survival, although it is argued whether this difference is clinically significant. While the quality of the data limit the strength of our conclusions, and while tumor characteristics, patient risk factors, and preferences should be considered, most data support that lobectomy and total thyroidectomy yield comparable oncologic outcomes for PTC measuring 1.0-4.0cm.

A protocol for a Canadian prospective observational study of decision-making on active surveillance or surgery for low-risk papillary thyroid cancer

IntroductionLow-risk papillary thyroid cancer (PTC) is increasingly being diagnosed throughout the world; yet the mortality risk is low compared with other malignancies. Traditional management includes thyroid surgery, sometimes followed by...

Extent of Initial Surgery May Impact Overall Survival, Even for Low-Risk Papillary Thyroid Cancers

Extent of Initial Surgery May Impact Overall Survival, Even for Low-Risk Papillary Thyroid Cancers

Active surveillance for low risk papillary thyroid cancer

We read with interest the article published by Akira Miyauchi, “Clinical Trials of Active Surveillance of Papillary Microcarcinoma of Thyroid” in the World Journal of Surgery [2016] (1), which summarizes 22 years of experience with this approach. Dr. Miyauchi, who is the father of active surveillance (AS) for low risk thyroid cancer, concludes that, “although we still offer two options, immediate surgery or observation, to patients with low risk papillary micro-carcinoma (PMC) at Kuma Hospital, we now strongly recommend observation as the best choice.”

Management of Low-Risk Papillary Thyroid Cancer.

The incidence of thyroid cancer has increased, mainly due to the incidental finding of low-risk papillary thyroid cancers (PTC). These malignancies grow slowly, and are unlikely to cause morbidity and mortality. New understanding about the prognosis of tumor features has led to reclassification of many tumors within the low-risk thyroid category, and to the development of a new one “very low-risk tumors.” Alternative less aggressive approaches to therapy are now available including active surveillance and minimally invasive interventions. In this narrative review, we have summarized the available evidence for the management of low-risk PTC.

Clinical implications of pathologic factors after thyroid lobectomy in patients with papillary thyroid carcinoma

ObjectiveWe evaluated the clinical and prognostic significance of pathologic factors by analyzing the treatment results of patients who underwent thyroid lobectomy. Materials and methodsWe retrospectively analyzed data from 734 patients diagnosed with papillary thyroid cancer who underwent thyroid lobectomy at Korea University Hospital from January 2004 to December 2016. ResultsA total of 734 patients were included in the study and their mean age was 44.5 years (range, 15–83). On univariate analysis, tumor size and recurrence-free survival were significantly related. The 10-year recurrence-free survival was 98.3% for tumors ≤1cm, 77.8% for >1cm and ≤2cm, and 66.7% for >2cm (p = 0.014). Recurrence-free survival was significantly different between patients with and without microscopic extrathyroidal extension (p=0.002). The 10-year recurrence-free survival rate was 99.2% for patients without extrathyroidal extension and 92.2% for patients with microscopic extrathyroidal extension. Multivariate analysis showed only microscopic extrathyroidal extension was significantly correlated with recurrence-free survival (p=0.029). ConclusionIn patients undergoing thyroid lobectomy for low-risk papillary thyroid cancer, microscopic extrathyroidal extension was an important prognostic factor associated with recurrence-free survival. However, in cases with microscopic extrathyroidal extension findings on postoperative pathologic examination, appropriate ultrasonographic follow-up of the contralateral thyroid lobe and cervical lymph node to facilitate early detection and prompt treatment of recurrence can control the disease without a deterioration of survival rate.

Most Low-Risk Papillary Thyroid Cancers Remain Stable During Active Surveillance

Most Low-Risk Papillary Thyroid Cancers Remain Stable During Active Surveillance

Natural History and Tumor Volume Kinetics of Papillary Thyroid Cancers During Active Surveillance

Active surveillance of low-risk papillary thyroid cancer (PTC) is now an accepted alternative to immediate surgery, but experience with this approach outside of Japan is limited. The kinetics (probability, rate, and magnitude) of PTC tumor growth under active surveillance have not been well defined. To describe the kinetics of PTC tumor growth during active surveillance. Cohort study of 291 patients undergoing active surveillance for low-risk PTC (intrathyroidal tumors ≤1.5 cm) with serial tumor measurements via ultrasonography at a tertiary referral center in the United States. Active surveillance. The cumulative incidence, rate, and magnitude of the change in tumor diameter or volume, as well as associations with patient and tumor characteristics. Of the 291 patients, 219 (75.3%) were women; mean (SD) age was 52 (15) years. During a median (range) active surveillance of 25 (6-166) months, growth in tumor diameter of 3 mm or more was observed in 11 of 291 (3.8%) patients, with a cumulative incidence of 2.5% (2 years) and 12.1% (5 years). No regional or distant metastases developed during active surveillance. In all cases, 3-dimensional measurements of tumor volume allowed for earlier identification of growth (median, 8.2 months; range, 3-46 months before increase in tumor diameter). In multivariable analysis, both younger age at diagnosis (hazard ratio per year, 0.92; 95% CI, 0.87-0.98; P = .006) and risk category at presentation (hazard ratio for inappropriate, 55.17; 95% CI, 9.4-323.19; P < .001) were independently associated with the likelihood of tumor growth. Of the tumors experiencing volume growth, kinetics demonstrated a classic exponential growth pattern, with a median doubling time of 2.2 years (range, 0.5-4.8 years; median r2 = 0.75; range, 0.42-0.99). The rates of tumor growth during active surveillance in a US cohort with PTCs measuring 1.5 cm or less were low. Serial measurement of tumor volumes may facilitate early identification of tumors that will continue to grow and thereby inform the timing of surveillance imaging and therapeutic interventions.

Multifocality and Hashimoto’s thyroiditis as independent predictors of structural recurrence in a cohort of low risk intrathyroidal papillary thyroid cancer.

e17577 Background: Increasing incidence of thyroid malignancies is almost totally attributable to papillary thyroid cancer (PTC). Although all disease stages are involved, PTCs confined to the thyroid were those with the higher trend. The absence of dedicated randomized controlled trials makes challenging the management of these low risk PTC at different steps of the therapeutic process (extent of surgery, prophylactic central node dissection, and radio-iodine treatment). Thus, it is mandatory to set a prognostic system suitable for this clinical setting. We analyzed prognostic factors of structural recurrence in a large cohort of consecutive low-risk intra-thyroidal PTC. Methods: Multicenter retrospective study including pT1/2 PTC without any evidence of extra-thyroidal disease. The following parameters were considered: gender, age at diagnosis, histology, tumour size, multifocality, pathologically-proven Hashimoto’s thyroiditis (HT), and radiometabolic treatment (RAI). The parameters significantly associated with structural recurrence at the univariate analysis ( p &lt; 0.05) were included in the multivariate analysis. Results: We included 284 patients (mean follow-up 6.3 yrs). At univariate analysis, parameters achieving significance were: age at diagnosis ≥ 45 yrs (p = 0.001, OR 0.04, 95% CI 0-0.72), microcarcinoma (p &lt; 0.001, OR 0.02, 95% CI 0-0.39), multifocality (p &lt; 0.001, OR 4.3, 95% CI 1.88-9.84), HT (p = 0.018, OR 0.33, 95% CI 0.13-0.86), and RAI (p = 0.002, OR 19.43, 95% CI 1.16-323.3). At multivariate analysis, only multifocality (p = 0.042, OR 2.52, 95% CI 1.03-6.16) and HT (p = 0.036, OR 0.34, 95% CI 0.12-0.93) revealed as independent prognosticators. Conclusions: Our data show that multifocality and HT should be considered as the main parameters for the decision-making of low risk PTC. Further studies are required. Note: We acknowledge Umberto Veronesi Foundation for granting Vincenzo Marotta with Post-doctoral Fellowship year-2017 Award.

Use of Personalized Post-Total Thyroidectomy Criteria in Low and Intermediate Risk Papillary Thyroid Cancer Patients to avoid Routine Radioactive Iodine Administration

Use of Personalized Post-Total Thyroidectomy Criteria in Low and Intermediate Risk Papillary Thyroid Cancer Patients to avoid Routine Radioactive Iodine Administration

Clinicopathological relevance of antithyroglobulin antibodies in low-risk papillary thyroid cancer.

The extent of initial surgical management in papillary thyroid cancer (PTC) is controversial. We examined whether the presence of perioperative antithyroglobulin antibodies (TGA) could predict long-term recurrence and occurrence of adverse features among a homogenous group of patients with PTC. The clinical features of patients with PTC treated at a single institution (Jewish General Hospital, McGill University, Montreal, Canada) were obtained from the medical records, and all clinicopathologic information was reviewed. Only low-risk PTC without clinical evidence of nodal disease before surgery and treated with 30 mCi of radioactive iodine was included in the study. The chart review retrieved 361 patients with a median follow-up of 85.0 months (Q25-Q75 73-98). Forty-two (11.6%) patients had presence of perioperative TGA. Perioperative TGAs were associated with present extrathyroidal extension (P=.005), unsuspected nodal disease (P=.001) and autoimmune thyroiditis (P<.0001). Overall, 17 (4.7%) patients experienced locoregional recurrence. Perioperative TGAs were a significant predictor of recurrence in univariable (P=.021) but not in multivariable analysis (P=.13). Presence of perioperative TGAs is associated with aggressive histological features and the presence of thyroiditis. Detection of TGA perioperatively may encourage surgeons to consider more extensive initial surgery.

Active Surveillance of Small, Low-Risk Papillary Thyroid Cancers Can Be a Safe Alternative to Surgery in Selected Patients

Active Surveillance of Small, Low-Risk Papillary Thyroid Cancers Can Be a Safe Alternative to Surgery in Selected Patients

Applying Criteria of Active Surveillance to Low-Risk Papillary Thyroid Cancer Over a Decade: How Many Surgeries and Complications Can Be Avoided?

The 2015 American Thyroid Association guidelines acknowledged that "an active surveillance management approach can be considered as an alternative to immediate surgery" in patients with low-risk papillary thyroid carcinoma (PTC). The aim of this study was to determine the proportion of PTC that would meet the criteria for active surveillance and the surgeries and complications that could have been avoided. A total of 681 patients with thyroid cancer who underwent thyroid surgery from 2003 to 2012 were retrospectively reviewed. A decision-making framework for active surveillance was applied to patients with PTC in nodules measuring ≤1.5 cm on ultrasound. Patients were identified as suitable for active surveillance based on imaging and patient characteristics. These patients were reviewed for management and outcomes. PTC was diagnosed based on fine-needle aspiration histology of Bethesda V or VI in thyroid nodules in 243 patients. Of these, 77 patients had nodules measuring ≤1.5 cm on ultrasound, and 56/77 (23%) patients met the criteria for surveillance: 15/243 (6%) patients met the criteria with a ≤1 cm size threshold, and 41/243 (17%) met the criteria with a 1.1-1.5 cm threshold. Of the 56 patients who met the criteria for active surveillance, 52 underwent total thyroidectomy, and four had a lobectomy. Forty-five (80%) patients had elective central nodal dissection, and 14 had nodal metastases on pathology (all <4 mm). Three patients had permanent complications from surgery, including vocal cord paralysis, hypoparathyroidism, and a chipped tooth from intubation. No patients died or had recurrent disease. Future programs in the United States should consider increasing the size threshold for active surveillance of PTC to 1.5 cm, since this will allow up to one quarter of patients to be eligible instead of only 6% with a 1 cm size threshold. Without an active surveillance program, the majority of patients with low-risk cancers have thyroidectomy and carry a small risk of permanent complications.

The Impact of Pathologically Positive Lymph Nodes in the Clinically Negative Neck: An Analysis of 39,301 Patients with Papillary Thyroid Cancer.

Management of patients with low-risk papillary thyroid cancer (PTC) with clinically uninvolved lymph nodes (cN0 LNs), but who harbor metastatic central LNs (pN1a), remains unclear. The number of central LNs examined, radioactive iodine (RAI) utilization, and survival were compared across cN0 patients based on pN stage: pN0 (negative) versus pNx (unknown) versus pN1a (pathologically positive). Adults with a PTC≥1cm who were cN0 preoperatively were compared based on surgical pathology using the National Cancer Data Base (NCDB; 2003-2011), after univariate and multivariate adjustment. Overall survival (OS) was examined using Kaplan-Meier curves, the log-rank test, and Cox proportional hazards modeling. Overall, 39,301 patients were included; median tumor size was 1.9cm. More LNs were examined for pN1a versus pN0 diagnosis (pN1a median=5 LNs vs. pN0 median=2 LNs; p<0.0001), with a median of two central LNs found to be positive on surgical resection. Compared with pN0, pN1a patients were 78% more likely to receive RAI (odds ratio 1.78, 95% confidence interval [CI] 1.65-1.91; p<0.0001). After adjusting for receipt of RAI, no difference in OS was observed for pN1a versus pN0 or pNx patients (p=0.72). Treatment with RAI was associated with improved OS (hazard ratio 0.78, 95% CI 0.62-0.98, p=0.03), but the effect of RAI did not differ based on pN stage (interaction p=0.67). More LNs were examined for positive versus negative pN diagnosis in patients with cN0 PTC. Unsuspected central neck nodal metastases in cN0 PTC patients are associated with increased RAI utilization, but no survival difference.

Risk Factors Associated with Disease Recurrence among Patients with Low-Risk Papillary Thyroid Cancer Treated at the University of the Philippines-Philippine General Hospital.

BackgroundThe management of papillary thyroid carcinoma (PTC) in high-risk patients is well-standardized. However, this is not the case for low-risk patients. Filipinos show a high incidence of recurrence of thyroid cancer. Thus, the identification of risk factors for recurrence in this population could potentially identify individuals for whom radioactive iodine (RAI) therapy might be beneficial.MethodsWe reviewed the medical records of adult Filipinos with low-risk PTC who underwent near-total or total thyroidectomy at the University of the Philippines-Philippine General Hospital. Multivariate logistic regression analysis was used to determine risk factors for recurrence.ResultsRecurrence was documented in 51/145 of patients (35.17%) included in this study. Possible risk factors such as age, sex, family history, smoking history, tumor size, multifocality, prophylactic lymph node dissection, initial thyroglobulin (Tg) level, initial anti-thyroglobulin (anti-Tg) antibody concentration, suppression of thyroid stimulating hormone production, and RAI therapy were analyzed. Multivariate analysis revealed that a tumor diameter 2 to 4 cm (odds ratio [OR], 9.17; 95% confidence interval [CI], 1.62 to 51.88; P=0.012), a tumor diameter >4 cm (OR, 16.46; 95% CI, 1.14 to 237.31; P=0.04), and a family history of PTC (OR, 67.27; 95% CI, 2.03 to 2228.96; P=0.018) were significant predictors of recurrence. In addition, RAI therapy (OR, 0.026; 95% CI, 0.01 to 0.023; P≤0.005), an initial Tg level ≤2 ng/mL (OR, 0.049; 95% CI, 0.01 to 0.23; P≤0.005), and an anti-Tg antibody level ≤50 U/mL (OR, 0.087; 95% CI, 0.011 to 0.67; P=0.019) were significant protective factors.ConclusionA tumor diameter ≥2 cm and a family history of PTC are significant predictors of recurrence. RAI therapy and low initial titers of Tg and anti-Tg antibody are significant protective factors against disease recurrence among low-risk PTC patients.

A systematic review of primary active surveillance management of low-risk papillary carcinoma.

Active surveillance is close follow-up of neoplasms, with predetermined intervention triggers. We systematically reviewed the published English language literature on primary active surveillance of low-risk papillary thyroid cancer (PTC). We searched seven electronic databases (1980-2015), supplemented with a hand search. Two reviewers independently screened 1715 citations and reviewed 32 full-text papers, ultimately including two papers. Data were independently abstracted. There were two Japanese single-center, single-arm studies reporting on 1235 and 322 patients with PTC microcarcinoma (primary ≤1 cm in diameter) confined to the thyroid. Mean study follow-up was of 5.0 and 6.5 years, respectively. Disease triggers for thyroidectomy included progression of the primary tumor or incident metastatic disease. The rates of thyroidectomy were 15.5% (191/1235) and 8.7% (28/322) in respective studies. The incidence of primary tumor enlargement ≥3 mm in maximal diameter was 4.6% (58/1235) and 5.0% (16/322). The incidence of nodal metastases was 1.5% (19/1235) and 0.9% (3/322). There were neither reports of PTC-related death nor development of distant metastatic disease. Quality of life, psychosocial health, and economic outcomes were not reported. In two Japanese single-arm studies, active surveillance of PTC microcarcinoma was relatively well tolerated; however, more long-term outcome research is needed.