Small Thyroid Cancers Research Articles

Are we ready to bridge classification systems? A comprehensive review of different reporting systems in thyroid cytology.

The evaluation of thyroid lesions is common in the daily practice of cytology. While the majority of thyroid nodules are benign, in recent decades, there has been increased detection of small and well-differentiated thyroid cancers. Combining ultrasound evaluation with fine-needle aspiration cytology (FNAC) is extremely useful in the management of thyroid nodules. Furthermore, the adoption of specific terminology, introduced by different thyroid reporting systems, has helped effectively communicate thyroid FNAC diagnoses in a clear and understandable way. In 1996, the Papanicolaou Society thyroid cytological classification was introduced. This was followed in 2005 by the first Japanese and then in 2007 by the Bethesda System for Reporting Thyroid Cytopathology, which subsequently underwent two revisions. Other international thyroid terminology classifications include the British, Italian, Australasian and other Japanese cytology systems. This review covers similarities and differences among these cytology classification systems and highlights key points that unify these varied approaches to reporting thyroid FNAC diagnoses.

Laser Ablation for Benign and Malignant Thyroid Nodules - A Mini-Literature Review.

Thyroid nodules are a common disease in endocrine clinical practice. They are often benign, asymptomatic, and do not require any treatment. But, in a non-negligible proportion, they can cause local symptoms of compression or esthetic concerns. In the last two decades, the advent of laser ablation (LA) has become a valid alternative to surgery for these nodules. Moreover, LA has also been successfully used to treat small thyroid cancers and neck recurrence. This study aims to review and summarize the published literature regarding LA in the treatment of benign and malignant thyroid nodules. A comprehensive literature search on PubMed from 2000 to 2023 was carried out. The search terms included: thyroid, nodules, laser, cancer, lymph node metastasis, and autonomously functioning nodules. The most relevant investigations in the field were selected. In the last two decades, a very remarkable number of papers consistently demonstrated that LA is able to durably shrink benign nodules on average by about 50%; better results are obtained in spongiform nodules with a volume less than 15 ml; 500 J/ml of tissue should be administered. LA may be a valid option to treat autonomously functioning nodules and papillary thyroid cancers especially if they are <10 mm, and with neck recurrence in patients already submitted to surgery. LA has also been demonstrated to be cost-effective compared to surgical treatment both in benign and malignant lesions, with similar outcomes. Evidence demonstrated that LA is a valid alternative to surgery in benign and malignant thyroid lesions, but also to obtain a successful treatment, a careful selection of the lesion is mandatory.

Abstract B102: Development of covalent inhibitors targeting Ras Q61 hotspot mutants

Abstract Mutations in the proto-oncogenes RAS are a key driver of various cancers, including pancreatic, colorectal, non–small cell lung cancer (NSCLC), melanoma, and thyroid cancer. Despite being considered undruggable for many years, recent efforts have led to the FDA approval of two drugs, Sotorasib and Adagrasib. They covalently target the K-Ras mutant isoform K-Ras(G12C), thereby inhibiting its oncogenic effect. However, the use of these drugs is inherently limited to cancers driven by the K-Ras(G12C) mutant, which is very common only in NSCLC. Although other covalent inhibitors targeting the K-Ras mutants K-Ras(G12S) and K-Ras(G12R) have been developed, it has so far not been possible to target the other frequently mutated amino acid Q61. Here we present our approach for the development of novel covalent inhibitors specifically targeting Q61 mutations in Ras proteins, which are prevalent in melanoma, multiple myeloma, and thyroid cancer. We demonstrate how covalent inhibitors specifically react with the mutant Q61C in both K and H-Ras proteins as proof-of-concept and show our efforts to extend this to the other Q61 mutant isoforms. We base our strategy on the modification of well-established switch-II pocket K-Ras inhibitors and explore multiple novel scaffolds specifically designed to target mutations of Q61. In addition to its occurrence in various cancers, Ras(Q61X) is also a common resistance mutation in patients treated with MAPK inhibitors. This work could further increase the number of patients potentially benefiting from Ras(Q61X) targeting drugs. Citation Format: Julius Pampel, Johannes Morstein, Qinheng Zheng, David M. Peacock, Kevan M. Shokat. Development of covalent inhibitors targeting Ras Q61 hotspot mutants [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr B102.

Radiofrequency Ablation of Small Thyroid Cancer–A Solution Looking for a Problem?

Radiofrequency Ablation of Small Thyroid Cancer–A Solution Looking for a Problem?

ZFPM2-AS1: An Oncogenic Long Non-coding RNA in Multiple Cancer Types.

Long non-coding RNA (lncRNA) is a novel kind of RNA transcript with lengths greater than 200 nucleotides. Functionally, lncRNAs lack the potential to encode peptides or proteins. Previous studies unveiled that lncRNA participated in numerous physiological and pathological processes, including cancer, aging, and immune responses. Newly discovered long noncoding RNA zinc finger protein, Friend of GATA (FOG) family member 2-antisense 1 (ZFPM2-AS1), located on the 8q23 chromosome, acts as a tumor stimulator in various cancer types, including Breast Cancer (BC), Colorectal Cancer (CRC), Esophageal Squamous Cell Carcinoma (ESCC), Gastric Cancer (GC), glioma, hepatocellular carcinoma (HCC), Lung Adenocarcinoma (LUAD), melanoma, non-small cell lung cancer (NSCLC), Retinoblastoma (RB), Small Cell Lung Cancer (SCLC) and thyroid cancer. Accumulative evidence also elucidated that ZFPM2-AS1 dysregulation was related to tumor proliferative, migratory, invasive, anti-apoptotic, and pro-epithelial-tomesenchymal Transition (EMT) effects, larger tumor volume, higher tumor weight, advanced tumor stage, high rates of lymphatic metastasis, distant metastasis, poor prognosis, histological differentiation, higher TNM (tumor, node, metastases) stage, depth of tumor invasion, reduced overall and disease- free survival, vein invasion, and shorter 5-year overall survival. Mechanistically, ZFPM2-AS1 acted as a ceRNA to play its oncogenic role. Thus, this study summarized the specific mechanisms of the lncRNA ZFPM2-AS1 in the aforementioned cancer types to reveal its novel application in cancer diagnosis, treatment, and prognosis.

Tumour volume is a predictor of lymphovascular invasion in differentiated small thyroid cancer.

For small thyroid cancers (≤2 cm), tumour volume may better predict aggressive disease, defined by lymphovascular invasion (LVI) than a traditional single measurement of diameter. We aimed to investigate the relationship between tumour diameter, volume and associated LVI. Differentiated thyroid cancers (DTC) ≤ 2 cm surgically resected between 2007 and 2016 were analysed. Volume was calculated using the formula for an ellipsoid shape from pathological dimensions. A 'larger volume' cut-off was established by receiver operating characteristic (ROC) analysis using the presence of lateral cervical lymph node metastasis (N1b). Logistic regression was performed to compare the 'larger volume' cut-off to traditional measurements of diameter in the prediction. During the study period, 2405 DTCs were surgically treated and 523 met the inclusion criteria. The variance of tumour volume relative to diameter increased exponentially with increasing tumour size; the interquartile ranges for the volumes of 10, 15 and 20 mm diameter tumours were 126, 491 and 1225 mm3, respectively. ROC analysis using volume to predict N1b disease established an optimal volume cut-off of 350 mm3 (area under curve = 0.59, P = 0.02) as 'larger volume'. 'Larger volume' DTC was an independent predictor for LVI in multivariate analysis (odds ratio (OR) = 1.7, P = 0.02), whereas tumour diameter > 1 cm was not (OR = 1.5, P = 0.13). Both the volume > 350 mm3 and dimension > 1 cm were associated with greater than five lymph node metastasis and extrathyroidal extension. In this study for small DTCs ≤ 2 cm, the volume of >350 mm3 was a better predictor of LVI than greatest dimension > 1 cm.

Factors That Inform Individual Decision Making Between Active Surveillance, Hemithyroidectomy and Total Thyroidectomy for Low-Risk Thyroid Cancer: A Scoping Review.

Background: Due to the excellent prognosis and relatively high incidence of small low-risk thyroid cancers, more conservative management strategies such as active surveillance (AS) or hemithyroidectomy (HT) may be preferable to total thyroidectomy (TT) for patients seeking to balance long-term survival rates with the potential adverse effects of overtreatment. The aim of this review was to synthesize key factors or variables that inform patient decision making about treatment for low-risk thyroid cancer, from current primary investigations that presented participants with information facilitating this choice. Methods: Studies were identified from the Medline, Cochrane, and Embase databases up until March 2022. Study characteristics were extracted into a pre-piloted form. Factors were hypothesized to include treatment-related risks and possible outcomes and identified from a review of studies with consensus by discussion. Results: The search identified 444 unique studies: 397 were excluded on review of abstract and title with 47 studies undergoing a full text review and 6 studies identified to be eligible. Four were cross-sectional: one a prospective cohort study and one a mixed-methods study with both a prospective observational and qualitative component. The decisions addressed included: the choice between AS versus surgery (HT and/or TT) and HT versus TT and enrolled participants ranging from healthy volunteers to thyroid cancer patients. Treatment choice was the primary outcome in five studies. Across the studies, participants who were given the option of AS or surgery predominately chose the more conservative pathway, with a range of 70-84%. The major factors represented by information provision in the studies were risk of cancer recurrence or spread, need for hormone replacement therapy, and voice change. Conclusions: A framework of key factors informing patient treatment choice may be derived from current studies involving information provision for low-risk thyroid cancer management. Further research evaluating the efficacy and optimal timing for decision support interventions would help inform the design and clinical use of these tools to promote shared decision making.

The Treatment of Thyroid Cancer With Radiofrequency Ablation

In the past decade, there has seen been a shift from treating all thyroid cancer surgically, to favoring less aggressive approaches for low-risk thyroid cancer. Surgery was historically the treatment of choice for most thyroid cancer. Active surveillance has emerged as an alternative for low-risk thyroid cancer in select patients. This approach has been accepted worldwide, and sound evidence supports its oncological safety in carefully selected patients. However, not all patients want to undergo lifelong monitoring, and some patients may wish to treat their cancer in a minimally invasive manner. Thermal ablation has developed as a minimally invasive alternative to surgery and active surveillance for well selected patients with thyroid malignancy. Herein, we review the role of thermally ablative techniques, specifically radiofrequency ablation, for the treatment of small primary thyroid cancers, recurrent thyroid cancer, and lymph node metastases.

Incidence and prognosis of thyroid cancer in children: based on the SEER database

ObjectiveTo update the recognition of the trends in the incidence of childhood thyroid cancer (TC) and its prognosis.MethodsA large-scale sample based on long time-line public database was recruited. Join-point regression model was used to analyze the incidence trend of childhood TC. Univariable and multivariable Cox regression model analyses were applied to explore the survival situation and prognostic factors.ResultsThe incidence rate of childhood TC increased between 1975 and 2016 from 3.8/million (95% CI 2.6–5.5) to 11.5/million (95% CI 9.2–14.1), AAPC = 2.38% (95% CI 1.98–9.65) and could be divided into two stages of increasing trends. The incidence rate of Trend1 (1975–2005) increased slowly (APC = 1.08%, 95% CI 0.38–1.82) while Trend2 (2005–2016) increased dramatically (APC = 6.77%, 95% CI 4.30–9.28). Annual incidence rate of small size tumor (< 4 cm) and local stage childhood TC increased significantly. The overall cumulative survival rate for childhood TC was high up to 97–99%. Males, black race, MTC type, distant metastasis, tumor size ≥ 4 cm, non-primary cancer were the independent risk factors of childhood TC prognosis.ConclusionA contribution of overdetection to rising pediatric TC rates might not be able to rule out. For clinical implications, screening TC in children with potential specific risk factors is feasible. Over-treatment to small size and local stage TC in children should be avoided.

Radiofrequency Ablation for Thyroid Nodules and Cancer in the United States: Balancing a Transformation of Thyroid Care With Risk for Misuse

Radiofrequency ablation (RFA), the most commonly used image-guided thermal ablation technique for thyroid nodules and cancers, has the potential to dramatically change the landscape of thyroid tumor management. Pioneered in Asia and Europe, RFA is now used in the United States to noninvasively decrease the size of a subgroup of benign solid thyroid nodules when there are compressive symptoms and/or cosmetic concerns and, less frequently, to treat small thyroid cancers and isolated lymph node metastases.

Familial Risks and Proportions Describing Population Landscape of Familial Cancer

Simple SummaryFamilial cancer can be defined through the occurrence of the same cancer in two or more family members. Hereditary cancer is a narrower definition of high-risk familial aggregation through identified predisposing genes. The absence of correlation between spouses for risk of most cancers, particularly those not related to tobacco smoking or solar exposure, suggests that familial cancers are mainly due to genetic causes. The aim of the present study was to define the frequency and increased risk for familial cancer. Data on 31 of the most common cancers were obtained from the Swedish Family-Cancer Database and familial relative risks (SIRs) were estimated between persons with or without family history of the same cancer in first-degree relatives. Practically all cancers showed a familial risk, with an SIR most commonly around two, or a doubling of the risk because of family history.Background: Familial cancer can be defined through the occurrence of the same cancer in two or more family members. We describe a nationwide landscape of familial cancer, including its frequency and the risk that it conveys, by using the largest family database in the world with complete family structures and medically confirmed cancers. Patients/methods: We employed standardized incidence ratios (SIRs) to estimate familial risks for concordant cancer among first-degree relatives using the Swedish Cancer Registry from years 1958 through 2016. Results: Cancer risks in a 20–84 year old population conferred by affected parents or siblings were about two-fold compared to the risk for individuals with unaffected relatives. For small intestinal, testicular, thyroid and bone cancers and Hodgkin disease, risks were higher, five-to-eight-fold. Novel familial associations included adult bone, lip, pharyngeal, and connective tissue cancers. Familial cancers were found in 13.2% of families with cancer; for prostate cancer, the proportion was 26.4%. High-risk families accounted for 6.6% of all cancer families. Discussion/Conclusion: High-risk family history should be exceedingly considered for management, including targeted genetic testing. For the major proportion of familial clustering, where genetic testing may not be feasible, medical and behavioral intervention should be indicated for the patient and their family members, including screening recommendations and avoidance of carcinogenic exposure.

Update of Radiofrequency Ablation for Treating Benign and Malignant Thyroid Nodules. The Future Is Now.

Thermal and chemical ablation are minimally invasive procedures that avoid removal of the thyroid gland and target symptomatic nodules directly. Internationally, Radiofrequency ablation (RFA) is among one of the most widely used thermal ablative techniques, and is gaining traction in North America. Surgery remains the standard of care for most thyroid cancer, and in the right clinical setting, Active Surveillance (AS) can be a reasonable option for low risk disease. Minimally invasive techniques have emerged as an alternative option for patients deemed high risk for surgery, or for those patients who wish to receive a more active treatment approach compared to AS. Herein, we review the literature on the safety and efficacy of RFA for treating benign non-functioning thyroid nodules, autonomously functioning thyroid nodules, primary small low risk thyroid cancer (namely papillary thyroid cancer) as well as recurrent thyroid cancer.

Ultrasound-Based Indications for Thyroid Fine-Needle Aspiration: Outcome of a TIRADS-Based Approach versus Operators’ Expertise

Background: Thyroid nodule image reporting and data systems (TIRADS) provide the indications for fine-needle aspiration (FNA) based on a combination of nodule sonographic features and size. We compared the TIRADS-based recommendations for FNA with those based on the personal expertise of qualified US investigators in the diagnosis of thyroid malignancy. Methods: Seven highly experienced ultrasound (US) investigators from 4 countries evaluated, online, the US video recordings of 123 histologically verified thyroid nodules. Technical resources provided the operators with a diagnostic approach close to the real-world practice. Altogether, 4,305 TIRADS scores were computed. The combined diagnostic potential of TIRADS (TIRSYS) and the personal recommendations of the investigators (PERS) were compared against 3 possible goals: to recognize all malignant lesions (allCA), nonpapillary plus non-pT1 papillary cancers (nPnT1PCA), or stage II-IV cancers (st2-4CA). Results: For allCA and nPnT1PCA, TIRSYS had lower sensitivity than PERS (69.8 vs. 87.2 and 83.5 vs. 92.6%, respectively, p <0.01), while in st2-4CA the sensitivities were the same (99.1 vs. 98.6% and TIRSYS vs. PERS, respectively). TIRSYS had a higher specificity than PERS in all 3 types of cancers (p < 0.001). PERS recommended FNA in a similar proportion of lesions smaller or larger than 1 cm (76.9 vs. 82.7%; ns). Conclusions: Recommendations for FNA based on the investigators’ US expertise demonstrated a better sensitivity for thyroid cancer in the 2 best prognostic groups, while TIRADS methodology showed superior specificity over the full prognostic range of cancers. Thus, personal experience provided more accurate diagnoses of malignancy, missing a lower number of small thyroid cancers, but the TIRADS approach resulted in a similar accuracy for the diagnosis of potentially aggressive lesions while sparing a relevant number of FNAs. Until it is not clearly stated what the goal of the US evaluation is, that is to diagnose all or only clinically relevant thyroid cancers, it cannot be determined whether one diagnostic approach is superior to the other for recommending FNA.

MON-434 Encapsulated Follicular-Variant of Micropapillary Carcinoma Presenting with Distant Bony Metastasis

INTRODUCTION The incidence of thyroid cancer has risen steadily over the last decades, in part due to increasing diagnosis of apparently low-risk well-differentiated cancers. The outcomes of well-differentiated thyroid cancers, including follicular variant papillary thyroid carcinoma (PTC), are believed to be quite favorable, with a largely indolent benign course. We examine an encapsulated follicular-variant of micropapillary carcinoma presenting with distant bony metastasis. CASE 55-year-old lady presented to clinic after biopsy of iliac crest (IC) mass revealed thyroid tissue. One year prior she started having dull pain at right hip, attributed to increased physical activity. She noticed a tender “lump” on her right hip. CT revealed destructive right iliac 8 cm mass with extraosseous soft tissue component, central necrosis, and eccentric calcifications; and right ovarian cyst. Right IC biopsy was consistent with thyroid tissue with positive Thyroglobulin and TTF-1 immunostains. Physical exam was normal, except for mild tachycardia, hypertension, right flank large rounded mass fixed to IC, tender to palpation without erythema or warmth on overlying skin. Thyroid ultrasound showed normal thyroid gland except 5.58 x 6.22 x 7.76 mm left lobe nodule without increased vascularity but with coarse peripheral calcification. FNA was unsatisfactory. Thyroid function tests revealed undetectable TSH, elevated FT4, FT3, and markedly elevated thyroglobulin and TSI. PET/CT scan showed focal area of mild FDG avidity, corresponding to the right iliac crest mass, without additional areas of FDG avidity suggestive of metastatic disease or primary neoplastic process. Three weeks after presentation, patient began having symptoms of hyperthyroidism. As FT4 and FT3 continued to rise, she was started on propranolol and methimazole. Due to inadequate response, methimazole was switched to high dose propylthiouracil with mild improvement. Thyroid uptake and scan and SPECT-CT revealed increased thyroid uptake and thyromegaly consistent with Graves’ disease and redemonstrated large right IC lesion with increased uptake in the periphery and central photopenia, suggesting metastatic thyroid malignancy. Pathology from total thyroidectomy reported encapsulated follicular variant of PTC, confined to the left lobe of the thyroid, without extrathyroidal extension, greatest tumor dimension 0.6cm. As metastasis to the IC were unlikely to have originated from this small encapsulated thyroid cancer, it was recommended to proceed with right oophorectomy for suspected malignant struma ovarii and IC lesion debulking. Surgical pathology revealed right ovary and fallopian tube without pathologic changes or features of teratoma and tissue from right iliac mass consistent with PTC. Patient is off all antithyroid medications and remains biochemically euthyroid, awaiting radioactive iodine therapy.

Assessing non-aggressiveness of untreated, local and regional, papillary thyroid cancer.

With a steadily increasing thyroid cancer incidence, information regarding cancer aggressiveness is essential to determine which patients may be suitable for active surveillance. This study assessed the extent of non-aggressiveness of untreated, local and regional stage, papillary thyroid cancer. We used the Surveillance, Epidemiology, and End Results (SEER) registry and included 1423 local stage and 337 regional stage papillary thyroid cancer cases. Thyroid cancer specific survival was estimated conditional on the absence of death due to competing causes using competing risk methods. Stratified analyses were done to determine non-aggressiveness among different patient and tumor characteristics. The overall rate of non-aggressiveness for local stage thyroid cancer was 99.34% (95% CI: 99.33-99.35%), with a rate of non-aggressiveness of 98.85% (95% CI: 98.77-98.93%) for males and 99.48% (95% CI: 99.46-99.49%) for females (p=0.055). Rate of non-aggressiveness was significantly lower in patients >60years compared to patients ≤60years (p<0.001). Although the rate of non-aggressiveness was the same for tumors ≤10mm and tumors of 11-20mm, tumors measuring >20mm had a significantly lower rate of non-aggressiveness (p=0.002). The overall rate of non-aggressiveness for regional stage thyroid cancer was 72.58% (95% CI: 70.61-74.56%). We found high rates of non-aggressiveness in untreated, local stage, papillary thyroid cancer, particularly in younger patients with small (≤2 cm) thyroid cancer, suggesting that these patients may be good candidates for active surveillance.

Active surveillance for patients with very low-risk thyroid cancer.

Over the past 30 years in the United States, increasing identification of small thyroid nodules has led to a dramatic rise in the detection of small thyroid cancers, many of which are unlikely to progress to overt clinical disease. Because autopsy studies reveal that up to 30% of people harbor clinically occult thyroid cancers, the growing use of diagnostic technologies has identified an increasing number of small, clinically low risk papillary thyroid cancers (PTCs). In recent years, clinical practice has evolved to de‐intensify the treatment for PTCs, with fewer total thyroidectomy and nodal dissection procedures being performed, in favor of more limited operations. In addition, vigilant observation of selected low risk cancers has demonstrated outcomes comparable to those patients who undergo immediate surgical intervention. Active surveillance has emerged as a new option within the treatment algorithm of PTCs. There is now robust data from cancer centers in Japan and Korea which have reported excellent oncologic outcomes among patients undergoing active surveillance for PTC, as well as more recent, similar data from the United States. American Thyroid Association guidelines now include the option of active surveillance for appropriately selected patients with low‐risk PTC. With active surveillance now one option within the standard of care for patients with certain thyroid cancers, surgeons have become critical to facilitating shared decision‐making for patients facing this diagnosis.

Analysis of Cell-Free DNA from 32,989 Advanced Cancers Reveals Novel Co-occurring Activating RET Alterations and Oncogenic Signaling Pathway Aberrations.

RET is an emerging oncogenic target showing promise in phase I/II clinical trials. An understudied aspect of RET-driven cancers is the extent to which co-occurring genomic alterations exist and how they may impact prognosis or therapeutic response. Somatic activating RET alterations were identified among 32,989 consecutive patients with metastatic solid tumors tested with a clinical cell-free circulating tumor DNA (cfDNA) assay. This comprehensive next-generation sequencing (NGS) assay evaluates single-nucleotide variants, and select indels, fusions, and copy number gains in 68-73 clinically relevant cancer genes. A total of 176 somatic activating RET alterations were detected in 170 patients (143 fusions and 33 missense mutations). Patients had non-small cell lung (NSCLC, n = 125), colorectal (n = 15), breast (n = 8), thyroid (n = 8), or other (n = 14) cancers. Alterations in other oncogenic signaling pathway genes were frequently identified in RET-positive samples and varied by specific RET fusion gene partner. RET fusions involving partners other than KIF5B were enriched for alterations in MAPK pathway genes and other bona fide oncogenic drivers of NSCLC, particularly EGFR. Molecular and clinical data revealed that these variants emerged later in the genomic evolution of the tumor as mechanisms of resistance to EGFR tyrosine kinase inhibitors. In the largest cancer cohort with somatic activating RET alterations, we describe novel co-occurrences of oncogenic signaling pathway aberrations. We find that KIF5B-RET fusions are highly specific for NSCLC. In our study, only non-KIF5B-RET fusions contributed to anti-EGFR therapy resistance. Knowledge of specific RET fusion gene partner may have clinical significance.

Active Surveillance for Small Papillary Thyroid Cancer: A Systematic Review and Meta-Analysis.

Background: The rapid increase in the incidence of small papillary thyroid carcinoma (PTC) appears to be caused by the detection of small thyroid cancers. Active surveillance (AS) was therefore suggested to overcome this problem. As the results were favorable with low rates of size enlargement and lymph metastasis, the 2015 American Thyroid Association Management Guidelines endorsed AS as an alternative to immediate surgery. As the clinical value of AS is a subject of ongoing active discussions and surveys, we considered a systematic review and meta-analysis to be timely and necessary. Methods: Ovid-MEDLINE and EMBASE databases were searched up to January 5, 2019, for studies reporting patients who were followed up with AS for PTC. Data extraction and methodological quality assessment were performed independently by two radiologists. The primary outcomes were to identify the annual pooled proportions of size enlargement of 3 mm or more and the detection of lymph node metastases at a 5-year follow-up period. These were calculated using an inverse-variance weighting model. An additional outcome was evaluation of the reasons for surgery during AS. Results: The pooled proportion of size enlargement occurring at 5 years was 5.3% [95% confidence interval (CI), 4.4-6.4%], and the pooled proportion of 5-year lymph node metastasis was 1.6% [CI, 1.1-2.4%]. In many subjects undergoing delayed operations, the reasons for operation were often other than those of size enlargement or lymph node metastasis. Conclusions: AS is effective for the management of small PTC, with a low proportion of size enlargement or lymph node metastasis occurring at 5 years. However, a substantial proportion of the causes of delayed surgery were other than size enlargement or lymph node metastasis, and these situations need to be optimally managed.

Ethical issues raised by thyroid cancer overdiagnosis: A matter for public health?

Current practices of identifying and treating small indolent thyroid cancers constitute an important but in some ways unusual form of overdiagnosis. Overdiagnosis refers to diagnoses that generally harm rather than benefit patients, primarily because the diagnosed condition is not a harmful form of disease. Patients who are overdiagnosed with thyroid cancer are harmed by the psycho-social impact of a cancer diagnosis, as well as treatment interventions such partial or total thyroidectomy, lifelong thyroid replacement hormone, monitoring, surgical complications and other side effects. These harms seem to outweigh any putative benefit of knowing about a cancer that would not have caused problems if left undiscovered. In addition to harms to patients, thyroid cancer overdiagnosis leads to significant opportunity costs at a societal level, due to costs of diagnosis and treatment. Unlike many other overdiagnosed cancers, accurate risk stratification is possible with thyroid cancer. At the individual patient level, use of this risk information might support informed choice and/or shared decision-making, as mandated by clinical ethics frameworks. And this approach might, to some extent, help to reduce rates of diagnosis and intervention. In practice, however, it is unlikely to stem the rising incidence and associated harms and costs of overdiagnosed thyroid cancer, especially in situations where health professionals have conflicts of interest. We argue in this article that thyroid cancer overdiagnosis may be usefully understood as a public health problem, and that some public health approaches will be readily justifiable and are more likely to be effective in minimising its harms.

Thyrotropin Suppressive Therapy for Low-Risk Small Thyroid Cancer: A Propensity Score-Matched Cohort Study.

Thyrotropin (TSH) suppression has improved the clinical outcomes of patients with differentiated thyroid cancer (DTC). However, the efficacy of TSH suppressive therapy (TST) is unclear in patients with low-risk DTC. This study aimed to evaluate the efficacy of TST and optimal TSH levels of patients with low-risk DTC. This retrospective propensity score-matched cohort study included DTC patients (n = 446) who underwent lobectomy from 2002 to 2008 with or without TST (TST group and No-TST group). Disease-free survival (DFS) and dynamic risk stratification were compared between both groups using serum TSH levels. Approximately 74% of TST patients and 11% of No-TST patients had suppressed serum TSH levels (<2 mIU/L). The median follow-up period was 8.6 years. During follow-up, the disease recurred in 10 (2.7%) patients, with no significant difference in DFS between the groups (p = 0.63). The proportion of patients with excellent treatment response was similar between the TST (65.2%) and No-TST (64.4%) groups. Incomplete biochemical response was noted in 17.2% of the TST group patients and 9.4% of the No-TST group patients. No significant difference was observed in the DFS between both groups by comparing serum TSH level (p = 0.57). TST did not improve clinical outcomes, and serum TSH levels were not associated with recurrence in patients with low-risk small DTC. No clinical benefits were shown for TSH suppression in low-risk patients who underwent lobectomy. Thus, levothyroxine is not necessary for patients without evidence of hypothyroidism.