Low-risk Papillary Thyroid Microcarcinoma Research Articles

Greetings From the Editor of Clinical Thyroidology

Greetings From the Editor of <i>Clinical Thyroidology</i>

Thermal Ablation for Small Papillary Thyroid Cancer: A Systematic Review.

Background: Although clinical studies indicate that thermal ablation is effective in treating low-risk papillary thyroid microcarcinomas (PTMCs), the effectiveness of this treatment in patients with low-risk PTMC has not yet been systematically evaluated. Methods: Ovid-MEDLINE and EMBASE databases were searched for studies published through May 1, 2019, which report the efficacy of thermal ablation in patients with low-risk PTMCs. Data were extracted and methodological quality was assessed independently by two radiologists according to PRISMA guidelines. Results: This systematic review identified 503 low-risk PTMCs in 470 patients treated by thermal ablation from 9 studies. During follow-up, no patient experienced local tumor recurrence or distant metastasis, whereas two patients (0.4%) experienced lymph node (LN) metastasis. One patient (0.2%) developed a new PTMC, which was successfully treated by additional ablation. Five patients (1.1%) underwent delayed surgery after ablation, including the two patients with LN metastasis and three additional patients with unknown etiology. Conclusions: Thermal ablation is an excellent local tumor control method in patients with low-risk PTMCs. Strict inclusion criteria and technical expertise are required to obtain favorable results.

BRAF V600E status may facilitate decision-making on active surveillance of low-risk papillary thyroid microcarcinoma

IntroductionConservative active surveillance has been proposed for low-risk papillary thyroid microcarcinoma (PTMC), defined as ≤1.0 cm and lacking clinical aggressive features, but controversy exists with accepting it as not all such PTMCs are uniformly destined for benign prognosis. This study investigated whether BRAF V600E status could further risk stratify PTMC, particularly low-risk PTMC, and can thus help with more accurate case selection for conservative management. MethodsThis international multicenter study included 743 patients treated with total thyroidectomy for PTMC (584 women and 159 men), with a median age of 49 years (interquartile range [IQR], 39–59 years) and a median follow-up time of 53 months (IQR, 25–93 months). ResultsOn overall analyses of all PTMCs, tumour recurrences were 6.4% (32/502) versus 10.8% (26/241) in BRAF mutation-negative versus BRAF mutation-positive patients (P = 0.041), with a hazard ratio (HR) of 2.44 (95% CI (confidence interval), 1.15–5.20) after multivariate adjustment for confounding clinical factors. On the analyses of low-risk PTMC, recurrences were 1.3% (5/383) versus 4.3% (6/139) in BRAF mutation-negative versus BRAF mutation-positive patients, with an HR of 6.65 (95% CI, 1.80–24.65) after adjustment for confounding clinical factors. BRAF mutation was associated with a significant decline in the Kaplan–Meier recurrence-free survival curve in low-risk PTMC. ConclusionsBRAF V600E differentiates the recurrence risk of PTMC, particularly low-risk PTMC. Given the robust negative predictive value, conservative active surveillance of BRAF mutation-negative low-risk PTMC is reasonable whereas the increased recurrence risk and other well-known adverse effects of BRAF V600E make the feasibility of long-term conservative surveillance uncertain for BRAF mutation-positive PTMC.

Active Surveillance in Adults with Low-Risk Papillary Thyroid Microcarcinomas: A Prospective Study.

The acceptance and results of active surveillance in patients with low-risk papillary thyroid microcarcinomas (PTMC) are unknown in populations other than the Japanese population. This was the objective of the present prospective study. We selected patients ≥20 years who had thyroid nodules ≤1.2 cm with intermediate or high suspicion for malignancy on ultrasonography (US), not located near the recurrent laryngeal nerve and without extrathyroidal invasion or apparent lymph node metastases, whose cytology was suspicious (Bethesda V) or diagnostic (Bethesda VI) of papillary thyroid carcinoma. Patients who opted for active surveillance were followed up by biannual US. Fifteen patients (18.7%) readily opted for surgery and 12 (15%) for active surveillance. Fifty-three patients (66.2%) delegated the decision or wished to know the doctor's preference before deciding. After the doctor had declared his/her preference for active surveillance, 50 patients decided to have this management and three to have surgery. Only 1/70 patients exhibited tumor progression (growth associated with a suspicion of extrathyroidal invasion) after 30 months of follow-up. Two patients decided to have surgery during follow-up, although the indication was not defined by the study. A>50% reduction in tumor volume was observed in three patients. The study shows that active surveillance can be well accepted if doctors were convinced that it is the best option for patients with low-risk PTMC. At least the short-term results reproduced those observed in other populations, with tumor progression being uncommon.

Active Surveillance Versus Immediate Surgery: Questionnaire Survey on the Current Treatment Strategy for Adult Patients with Low-Risk Papillary Thyroid Microcarcinoma in Japan.

Background: Two Japanese prospective trials of active surveillance (AS) for adult patients with low-risk papillary thyroid carcinoma (PTC) ≤1 cm (cT1aN0M0 PTMC) have verified the safety of AS in oncological control and its superiority over immediate surgery with respect to unfavorable outcomes. Thus, AS has been accepted as an alternative to immediate surgery for asymptomatic papillary thyroid microcarcinomas (PTMCs). However, the real-world clinical approach for PTMC is unknown. Thus, this study aimed to investigate the current state of management of asymptomatic PTMCs in Japan.Methods: We conducted a questionnaire survey on the actual treatment patterns for adult patients with low-risk PTMCs. The subjects were member institutions of the Japan Association of Endocrine Surgery (JAES) or Japanese Society of Thyroid Surgery (JSTS), including the departments of surgery and head and neck surgery (HNS).Results: Responses were obtained from 134 institutes, where 72.4% of Japanese thyroid cancer cases operated by surgeons were treated. For suspicious tumors on ultrasound, 18 responders (13.4%) conducted cytological examination routinely, while 69 (51.5%) and 40 (27.8%) conducted it only for tumors >5 and >10 mm, respectively. After the diagnosis, 42 responders (31.3%) recommend AS, 35 (26.1%) recommend immediate surgery as the management, and 52 (38.8%) allowed patients to decide the treatment course. The present responders tended to recommend surgery for PTMCs that were located adjacent to the dorsal surface of the thyroid, were multiple, or measured almost 10 mm in size. At these institutions, 1176 patients with PTMC underwent surgery in 2017, accounting for 18.1% of surgeries for PTC. During the succeeding three months, 310 of 576 (53.8%) PTMC patients underwent AS. The treatment strategies did not differ between the departments (Surgery or HNS). The institutions that have six or more surgeons, that were located in metropolitan areas, or that were certified by JAES or JSTS performed AS more actively.Conclusion: More than 50% of low-risk PTMCs are on AS in Japan. However, the indication and recommendation for AS vary significantly between institutions. To improve the implementation of this management modality, physicians and patients should be further educated, and the sociomedical environment should be improved.

Does the ATA Risk Stratification Apply to Patients with Papillary Thyroid Microcarcinoma?

The incidence of papillary thyroid microcarcinoma (PTMC) has increased over the past decade. The American Thyroid Association (ATA) suggests that these patients may undergo either thyroid lobectomy or active surveillance. It remains unclear whether there exists a subgroup of PTMC patients who may benefit from more aggressive treatment due to increased risk of recurrence. We retrospectively reviewed 357 patients with PTMC who underwent surgery at a single institution from 2004 to 2016. Patients were classified according to 2015 ATA risk stratification for structural disease recurrence. Demographic, oncologic, and clinicopathologic data were compared between groups. Out of 357 patients, 246 were classified as low-risk PTMC, 93 were intermediate-risk, and 18 were high-risk. There were more male patients in the high-risk group (38.9%) than the intermediate- (31.2%) or low-risk groups (15.4%) (p < 0.001). Patients with low-risk microcarcinomas were more likely to have an incidental PTMC when compared to intermediate- or high-risk groups (98[39.8%], 15[16.1%], 1[5.6%], respectively, p < 0.001). Patients with high-risk PTMCs, compared to those with intermediate- and low-risk PTMCs, were more likely to have rising postoperative thyroglobulin levels after total thyroidectomy (6[40.0%], 4[5.1%], 9[5.7%], respectively, p = 0.001) and structural recurrence after lobectomy or total thyroidectomy (3[16.7%], 0[0%], 0[0%], respectively, p < 0.001). The median follow-up time was 17.5 (IQR 3-55) months. Patients with high-risk PTMC have an increased risk of recurrence when compared to low- and intermediate-risk microcarcinomas, whereas intermediate-risk PTMC may behave similarly to low-risk tumors. ATA risk stratification may inform clinical decision making for patients with PTMC.

Computed Tomography for Detecting Cervical Lymph Node Metastasis in Patients Who Have Papillary Thyroid Microcarcinoma with Tumor Characteristics Appropriate for Active Surveillance.

Background: Active surveillance (AS) has been considered one of the management options in patients with low-risk papillary thyroid microcarcinoma (PTMC). It is important to evaluate clinical lymph node (LN) metastasis to select appropriate candidates with low-risk disease. We investigated the predictive accuracy of computed tomography (CT) for cervical LN metastasis in patients who have PTMC with tumor characteristics appropriate for AS. Methods: This was a retrospective study. Medical records from December 2014 to the end of 2016 were reviewed. Patients who underwent thyroidectomy and who had pathologically confirmed PTMC were included. A total of 464 patients who had tumors with ultrasound (US) characteristics appropriate for AS and who underwent preoperative CT were included in the analysis. Results: CT showed higher diagnostic values especially in positive predictive value (PPV) than US. In patient-based analyses, CT showed low sensitivity and negative predictive value (NPV) (16.0% and 58.5%, respectively), but high specificity and PPV (99.6% and 97.1%, respectively) for detecting cervical LN metastasis. Similar trends were observed for the results of the central neck-level by CT (sensitivity, 14.9%; specificity, 97.4%; PPV, 82.9%; and NPV, 57.4%) in level-by-level analyses. When restricted to lateral neck levels, CT showed high diagnostic accuracy of 95.4% for detecting LN metastasis. In all analyses, CT showed better diagnostic values for cervical LN metastasis than US. Combining US and CT did not improve the diagnostic accuracy compared with CT. Conclusions: In patients with PTMC whose tumor has characteristics suitable for AS, CT had additional benefit after cervical LN assessment by US. Further studies are needed to evaluate routine initial CT scanning for patients who are candidates for AS.

Extensive lymphatic spread of papillary thyroid microcarcinoma is associated with an increase in expression of genes involved in epithelial‐mesenchymal transition and cancer stem cell‐like properties

BackgroundActive surveillance is an alternative management for patents with low‐risk papillary thyroid microcarcinoma (PTMC); however, there is an absence of specific molecular markers that predict its progression. We compared gene expression patterns between PTMC with lateral neck‐node metastasis (N1b) and PTMC‐lacking nodal metastasis (N0).MethodsWe performed oligonucleotide microarray analysis in three PTMCs without cervical lymph‐node metastases (N0), and five PTMCs with lateral neck‐node metastasis (N1b) at initial diagnosis, using an Illumina HumanHT‐12 v4.0 Expression BeadChip. Quantitative real‐time PCR (qPCR) and western blot analysis confirmed microarray data. We performed immunohistochemistry (IHC) to confirm protein overexpression in samples from 20 N0 and 24 N1b PTMC patients who underwent thyroidectomy.ResultsMicroarray analyses identified 52 probes corresponding to 45 genes. Expression of these genes differed significantly between the two PTMC groups. Forty genes were significantly upregulated and five genes were downregulated in N1b PTMC compared to N0. Four genes related to epithelial‐to‐mesenchymal transition (EMT) and stem cell markers, including ALDH1A3, TM4SF1, PROM1, and CAV1 were significantly upregulated in N1b PTMCs. Real‐time qPCR confirmed this expression and western blot analysis confirmed higher expression of ALDH1A3, TM4SF1, PROM1, and CAV1 in N1b than in N0 PTMCs. IHC indicated overexpression of ALDH1A3 and CAV1 in N1b compared to N0 PTMCs.ConclusionsGenes related to EMT and thyroid cancer stem cell‐like properties are upregulated in early extensive lymphatic spread of PTMC.

Thyroid nodules ≤ 1 cm and papillary thyroid microcarcinomas: Brazilian experts opinion.

The indolent evolution of low-risk papillary thyroid microcarcinoma (mPTC) in adult patients and the consequences of thyroidectomy require a revision of the management traditionally recommended. Aiming to spare patients unnecessary procedures and therapies and to optimize the health system in Brazil, we suggest some measures. Fine-needle aspiration of nodules ≤ 1 cm without extrathyroidal extension on ultrasonography should be performed only in nodules classified as "very suspicious" (i.e., high suspicion according to ATA, high risk according to AACE, TI-RADS 5) and in selected cases [age < 40 years, nodule adjacent to the trachea or recurrent laryngeal nerve (RLN), multiple suspicious nodules, presence of hypercalcitoninemia or suspicious lymph nodes]. Active surveillance (AS) rather than immediate surgery should be considered in adult patients with low-risk mPTC. Lobectomy is the best option in patients with unifocal low-risk mPTC who are not candidates for AS because of age, proximity of the tumor to the trachea or RLN, or because they opted for surgery. The same applies to patients who started AS but had a subsequent surgical indication not due to a suspicion of tumor extension beyond the gland or multicentricity. Molecular tests are not necessary to choose between AS and surgery or, in the latter case, between lobectomy and total thyroidectomy. The presence of RAS or other RAS-like mutations or BRAFV600E or other BRAF V600E-like mutations should not modify the management cited above; however, the rare cases of mPTC exhibiting high-risk mutations, like in the TERT promoter or p53, are not candidates for AS.

Safety and efficacy of ultrasound-guided percutaneous thermal ablation in treating low-risk papillary thyroid microcarcinoma: A pilot and feasibility study.

This study aimed to evaluate the safety and efficacy of thermal ablation in treating low-risk unifocal papillary thyroid microcarcinoma (PTMC). Patients with unifocal PTMC were enrolled in this study, and thermal ablations were performed. Contrast-enhanced ultrasound was used to estimate the extent of ablation immediately after thermal ablation; complications were recorded. The size and volume of the ablated area and thyroid hormones were measured, and the clinical evaluations were performed at 1, 3, 6, 12, and 18 months after thermal ablation. From July 2016 to July 2017, the prospective study was conducted involving 107 patients. Thermal ablation was well tolerated without serious complications. Compared with the volume immediately after thermal ablation, the mean volume reduction ratio (VRR) of ablated lesions was 0.457 ± 0.218 (range: 0.040-0.979), 0.837 ± 0.150 (range: 0.259-1), 0.943 ± 0.090 (range: 0.491-1), 0.994-0.012 (range: 0.938-1), and 0.999 ± 0.002 (range: 0.992-1) at 1, 3, 6, 12, and 18 months after thermal ablation, respectively. Significant differences in the VRR were found between every two follow-up visits (P < 0.01). Results of patients' thyroid function test before thermal ablation and at 1 month after thermal ablation were normal, and no significant differences were observed (P > 0.05). No tumor regrowth, local recurrence, or distant metastases were detected during follow-up visits. Thermal ablation is a short-term safe and effective method in treating low-risk small PTMCs, which can be considered a potential alternative therapy for patients with PTMC.

US-Guided Radiofrequency Ablation for Low-Risk Papillary Thyroid Microcarcinoma: Efficacy and Safety in a Large Population.

To evaluate the efficacy and safety of radiofrequency ablation (RFA) for low-risk papillary thyroid microcarcinoma (PTMC) in a large population. Cases of 152 biopsy-proven PTMCs from 133 patients who had undergone RFA for PTMC between May 2008 and January 2017 were included in this study. All patients were either of high surgical risk or refused to undergo surgery. They were followed up for at least 6 months after initial RFA. Ultrasonography (US) and computed tomography were performed to evaluate the PTMC and the presence of neck metastasis before treatment. RFA was conducted using an internally cooled thyroid-dedicated electrode system. Follow-up US was performed at 1 week, and 2, 6, and 12 months, after the initial RFA, and then at every 6-12 months. We evaluated serial changes of ablated tumors, newly developed cancers, lymph node (LN) or distant metastasis and complications. Complete disappearance was found in 91.4% (139/152) of ablated tumors. Among the 13 tumors in patients who did not show complete disappearance, no tumor displayed any regrowth of the residual ablated lesion during the follow-up period. The mean follow-up period was 39 months. During the follow-up period, there were no local recurrence, no LN or distant metastasis, and no newly developed thyroid cancers. No patients were referred to surgery. The overall complication rate was 3% (4/133) of patients, including one voice change. There were no life-threatening complications or procedure-related deaths. Our results suggest that RFA is an effective and safe option for treating low-risk PTMC patients who are of high surgical risk or refuse surgery.

The Efficacy and The Safety of Ultrasound-guided Ablation Therapy for Treating Papillary Thyroid Microcarcinoma.

The prevalence of papillary thyroid microcarcinoma (PTMC) increases rapidly all around the world, but the management of PTMC hasn't reached a consensus. Recently, ultrasound-guided (US-guided) ablation therapy was introduced as a feasible treatment for low-risk PTMC. The clinical application of US-guided ablation therapy needs doctors' effort to investigate the efficacy and the safety of US-guided ablation in treating PTMC carefully. Although the present evidence showed some limitations, such as short-term study time spans and no randomized control design, in our perspective, US-guided thermal ablation therapy has good short-term efficacy and safety and is a promising PTMC's treatment in future clinical practice.

Active Surveillance for Papillary Thyroid Microcarcinoma: Challenges and Prospects.

Active surveillance (AS) can be considered as an alternative to immediate surgery in low-risk papillary thyroid microcarcinoma (PTMC) without clinically apparent lymph nodes, gross extrathyroidal extension (ETE), and/or distant metastasis according to American Thyroid Association. However, in the past AS has been controversial, as evidence supporting AS in the management of PTMC was scarce. The most prominent of these controversies included, the limited accuracy and utility of ultrasound (US) in the detection of ETE, malignant lymph node involvement or the advent of novel lymph node malignancy during AS, and disease progression. We summarized publications and indicated: (1) US, performer-dependent, could not accurately diagnose gross ETE or malignant lymph node involvement in PTMC. However, the combination of computed tomography and US provided more accurate diagnostic performance, especially in terms of selection sensitivity. (2) Compared to immediate surgery patients, low-risk PTMC patients had a slightly higher rate of lymph node metastases (LNM), although the overall rate for both groups remained low. (3) Recent advances in the sensitivity and specificity of imaging and incorporation of diagnostic biomarkers have significantly improved confidence in the ability to differentiate indolent vs. aggressive PTMCs. Our paper reviewed current imagings and biomarkers with initial promise to help select AS candidates more safely and effectively. These challenges and prospects are important areas for future research to promote AS in PTMC.

Active Surveillance of Low-Risk Papillary Thyroid Microcarcinoma: A Multi-Center Cohort Study in Korea.

Active surveillance has been introduced as a management option for low-risk papillary thyroid microcarcinoma (PTMC) due to its mostly indolent course. This was a multicenter study of 370 PTMC patients who underwent active surveillance more than one year. The changes in volume and maximum diameter between initial and last ultrasonography were evaluated to identify the natural course of PTMC during active surveillance. Patients' age at diagnosis was 51 ± 12 years, and 110 (30%) patients were <45 years of age. The initial maximum diameter and volume of PTMCs were 5.9 ± 1.7 mm and 81.0 ± 77.7 mm3, respectively. During the median 32.5 months of follow-up, 86 (23.2%) patients were found to have an increase in tumor volume, and 13 (3.5%) patients showed an increase in the maximal diameter of the tumor. The cumulative incidence of volume increase gradually rose with time (6.9%, 17.3%, 28.2%, and 36.2% after two, three, four, and five years, respectively). The risk of volume increase in patients <45 years of age was twice as high as in older patients (p = 0.002). There was no significant difference in tumor size change according to sex, levothyroxine treatment, or presence of Hashimoto's thyroiditis. During the period, 58 (15.7%) patients underwent delayed thyroid surgery due to anxiety (37.9%), tumor size increase (32.8%), or appearance of cervical lymph node metastasis (8.6%). Lymph node metastasis was found in 29.3% of patients on pathological examination. A significant number of PTMCs grow during active surveillance, and tumor volume change is a more sensitive means of evaluating tumor growth. Active surveillance can be carefully applied for selected patients. Although it is not contraindicated, it should be applied more cautiously for younger patients.

Active Surveillance as First-Line Management of Papillary Microcarcinoma.

Papillary thyroid microcarcinoma (PMC) is defined as papillary thyroid carcinoma ≤10 mm. Active surveillance of PMC without high-risk features, such as clinical node metastasis, distant metastasis, and clinical evidence of significant extrathyroid extension, was initiated in two Japanese hospitals in the mid-1990s. This strategy was incorporated into guidelines in Japan in 2010 and in the United States in 2015. In studies conducted by the two hospitals, most PMCs grew very slowly or did not grow, and none of the patients during active surveillance showed distant metastasis or died of thyroid carcinoma. Furthermore, none of the patients who underwent surgery after progression signs were detected showed significant recurrence. Therefore, we conclude that active surveillance should be the first line in management of low-risk PMC, because it is safer and less costly than immediate surgery. Active surveillance helps in avoiding adverse events of surgery and is an economical strategy.

Long-term oncologic outcomes of papillary thyroid microcarcinoma according to the presence of clinically apparent lymph node metastasis: a large retrospective analysis of 5,348 patients.

PurposeActive surveillance (AS) of low-risk papillary thyroid microcarcinoma (PTMC) may reduce the risk of overtreatment of clinically insignificant cancer. However, the absence of predictor for the progression of PTMC resulted in treatment delay and potentially compromising cure of aggressive disease. Therefore, to anticipate potential damage of delayed surgery, we investigated the oncologic outcomes of patients with low-risk PTMC initially eligible for AS except clinically apparent lymph node metastasis (LNM), imitating delayed surgery with neck dissection.Materials and methodsA total of 5,348 patients, enrolled between 1987 and 2016, with low-risk PTMC initially eligible for AS were included regardless of LNM. We classified our study patients into two groups: Group I, lobectomy with prophylactic central cervical node dissection; Group II, total thyroidectomy with modified radical neck dissection for LNM. In addition, we investigated the oncological outcomes of patients with second-wave surgery due to lateral lymph node recurrence (Group III, subgroup of Group I).ResultsGroup I showed more favorable clinicopathological characteristics compared with Group II. In Group I, only 29 (0.58%) of 4,927 patients underwent second-wave surgery with neck dissection for lateral lymph node recurrences, whereas in Group II, all 22 (5.23%) of 421 patients underwent second-wave selective node dissection because of nodal recurrence. Disease-free survival rates were significantly different between Groups I and II (P<0.05). Of note, the recurrence rate of Group II was still significantly higher than that of Group III (5.2% vs 0%, respectively; P=0.021). In addition, Kaplan–Mayer survival analysis indicated poor disease-free survival rates in Group II compared with Group III (P<0.05).ConclusionThe long-term treatment outcome of PTMC without LNM was favorable even if the recurrence occurs during follow-up period compared with that of PTMC with LNM. It should be noted that AS might be able to cause poor prognosis due to clinically apparent LNM.

Many Physicians Adopt Active Surveillance for Low-Risk Papillary Thyroid Microcarcinomas at Kuma Hospital

Many Physicians Adopt Active Surveillance for Low-Risk Papillary Thyroid Microcarcinomas at Kuma Hospital

Clinical management of papillary thyroid microcarcinoma

Papillary thyroid microcarcinoma(PTMC)of the thyroid is defined as papillary thyroid carcinoma measuring<1 cm. The incidence of differentiated thyroid cancer is increasing greatly. However, roughly half of this increase is attributable to the identification of PTMC. Serum thyroid stimulating hormone, thyroid ultrasound and ultrasound guided thyroid fine needle aspiration cytology(FNAC)are still the cornerstone for its diagnosis. The active surveillance approach in which active treatment is delayed until the cancer shows signs of substantial progression could be considered in selected patients with low-risk PTMC. Active surgery is still the first line treatment for other PTMC patients, although thermal ablation may be an alternative option for low-risk patients with PTMC. (Chin J Endocrinol Metab, 2018, 34: 353-358) Key words: Papillary thyroid microcarcinoma; Active surveillance; Thermal ablation

Trends in the Implementation of Active Surveillance for Low-Risk Papillary Thyroid Microcarcinomas at Kuma Hospital: Gradual Increase and Heterogeneity in the Acceptance of This New Management Option.

Background: Active surveillance (AS) of low-risk papillary thyroid microcarcinoma (PMC) was adopted as a management modality in both the Japanese guidelines in 2011 and the American Thyroid Association guidelines in 2015. AS was initiated at Kuma Hospital in 1993 but was not immediately accepted by all physicians. This study investigated the history of acceptance of AS at Kuma Hospital over time. The results should assist in the implementation of AS at other hospitals in Japan and other countries.Methods: This study included 4023 patients who were cytologically diagnosed with low-risk PMC at Kuma Hospital during the 24-year period between October 1993 and June 2016. The trend in the frequency of AS use over time was analyzed, dividing the 24-year study period into five parts based on the change in frequency of AS use: 1993–1997, 1998–2002, 2003–2006, 2007–2013, and 2014–2016.Results: The frequency of AS use in the present cohort was 65%. The frequency gradually increased from 30% in 1993–1997 to 88% in 2014–2016, with a slight decrease from 51% in 1998–2002 to 42% in 2003–2006. Until 2007, patients were mostly seen by surgeons, and the frequency of AS use varied remarkably among individual surgeons. Since 2007, the number of patients whose therapeutic strategies are determined by endocrinologists has increased, and the frequency of AS use for low-risk PMC by endocrinologists has been higher than that by surgeons.Conclusions: At Kuma Hospital, acceptance of AS for low-risk PMC gradually increased over the 24-year study period, but AS was not equally accepted by all physicians. Such variations in the acceptance of AS among individual physicians are also expected to exist in other hospitals. However, due to increasing evidence of the safety and superiority of AS over immediate surgery for this indolent disease, it is expected that AS will gain faster acceptance in other hospitals in Japan and around the world.

Can Active Surveillance Be An Alternative To Surgery In Papillary Thyroid Microcarcinoma?: The Current Situation In The World

Papillary thyroid carcinoma is the most common endocrine malignancy. Papillary thyroid microcarcinomas (PTMCs) are tumors with a size of ≤1 cm. The biological behavior of these tumors differs due to the presence of their aggressive features. The prognosis of PTMCs with high-risk features, such as clinical node metastasis, distant metastasis, and significant extrathyroidal extension to the tracheal or recurrent laryngeal nerve invasion, is poor, even if a sufficient immediate surgery is performed at diagnosis. However, PTMCs without these aggressive features are low-risk tumors because of their indolent and slow growth behaviors. The increase in thyroid cancer incidence is mostly a result of overdiagnosis of small low-risk PTMCs with indolent clinical course. Despite the sudden increase in thyroid cancer incidence worldwide, cancer mortality did not increase. Although the traditional treatment strategy for PTMC is immediate surgery at diagnosis, because of the rather low disease-specific mortality rate, low recurrence rate, and potential risk for postoperative complications, active surveillance has been proposed recently as an alternative option for PTMCs without invasion, metastasis, or cytological or molecular characteristics. The recent data support that active surveillance of low-risk PTMC should be the initial treatment modality, because only a small percentage of low-risk PTMCs show signs of progression, and delayed surgery has not caused significant recurrence. However, recent management guidelines are shifting toward more conservative treatments, such as active surveillance. Although there is an increase in the number of studies related to active surveillance, prospective studies have been mostly from academic referral centers in Japan. The world still needs class 1 evidence extended prospective studies originating from different geographic regions. Active surveillance may be a good alternative to immediate surgery for appropriately selected patients with PTMC.