Clinical management of papillary thyroid microcarcinoma

Quality of Life in Patients with Low-Risk Papillary Thyroid Microcarcinoma: Active Surveillance Versus Immediate Surgery

Thermal ablation presents a therapeutic option other than active surveillance and immediate surgery for patients with low-risk papillary thyroid microcarcinomas (PTMC). Here, we have reviewed the current oncologic outcome of thermal ablation in PTMC cases and compared it with active surveillance and surgery. Thermal ablation in PTMC cases revealed no tumor progression for pooled 5-year follow-up data. This oncologic outcome of thermal ablation was comparable to that of immediate surgery with less morbidity. Additionally, no patient who underwent thermal ablation received delayed surgery during the follow-up period due to anxiety. However, active surveillance has indicated that a substantial proportion (range, 8-32%) of patients underwent surgery mainly due to anxiety. In a subset of PTMC patients who are high-risk surgical candidates or who refuse surgery, especially those who have failed or are reluctant to pursue active surveillance, thermal ablation can be a good option.

Objective To compare the clinical features and 131I efficacy of papillary thyroid microcarcinoma (PTMC) and papillary thyroid carcinoma (PTC) except for PTMC. Methods PTC patients who were undergoing 131I treatment after total thyroidectomy were divided into the PTMC group (≤1.0 cm) and the papillary non-microcarcinoma group (>1.0 cm) according to tumor diameter. The clinical data of both groups were retrospectively analyzed, and the prognoses of the patients were evaluated. The statistical software SPSS Statistics 22.0 was used to analyze the results via t test and chi-squared (χ2) test. Results The proportion of patients with lymph node and central lymph node metastases in the PTMC group was lower than that in the PTC group. The number of metastatic lymph nodes was less, and the difference was statistically significant (χ2=44.23, 23.56, 42.80, all P 0.05). A total of 197 patients in the two groups achieved clinical remission after treatment. The remission rate in the PTMC group was higher than that in the PTC group. Among the 197 clinical remission cases, 102 patients achieved clinical remission after the first treatment. Although more patients achieved clinical remission in the PTMC group than in the PTC group after the first treatment, no significant difference was noted between the two groups (χ2=3.18, P>0.05). Conclusions The clinical features of PTMC patients differ from those of PTC patients. The overall cure rate of PTMC after 131I treatment is higher than that of PTC. The development of individualized treatment plans for PTMC patients is recommended to achieve good therapeutic effect and prognosis. Key words: Thyroid neoplasms; Iodine radioisotopes; Papillary thyroid microcarcinoma; Papillary thyroid carcinoma; Clinical feature; Prognosis

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.

Papillary thyroid microcarcinoma (PTMC) has an excellent prognosis; however, some PTMCs exhibit poor outcomes. Cancer-specific death from PTMC has been rarely reported, so we aimed to evaluate mortality rates and causes of death in patients who died with PTMC. We retrospectively reviewed 8969 PTMC patients treated at Samsung Medical Center from 1994 to 2017. Mortality rate and causes of death in PTMC patients were evaluated and compared with those of 7873 patients with papillary thyroid carcinoma (PTC) > 1 cm. In addition, we reviewed previous publications reporting cancer-specific deaths from PTMC. Among the 8969 PTMC patients, 107 (1.2%) patients died. Only two (0.02%) patients have died of PTMC, which was less than the cancer-specific deaths from PTC > 1 cm (0.71%). Among the deceased PTMC patients, 63 (58.9%) died of other malignancies, three (2.8%) died of cardiovascular diseases, and five (4.7%) died of other diseases. Compared with PTC > 1 cm, cancer-specific deaths was less (1.9% vs. 15.1%, P < 0.001), and deaths from other malignancies were higher in deceased PTMC patients (58.9% vs. 30.5%, P < 0.001). According to 18 studies, PTMC-specific mortality rates ranged from 0.05% to 14.3%, and 336 cancer-specific deaths (0.43%) occurred among 78,770 PTMC patients. The cancer-specific mortality rate of PTMC patients was extremely low (0.02%). More than half of deceased PTMC patients died of other malignancies, which was significantly more than those with PTC > 1 cm. These results support that active surveillance can be selected as a therapeutic option for PTMC.

The incidence of thyroid carcinoma has been increasing worldwide. This is interpreted as an increase in the incidental detection of papillary thyroid microcarcinomas (PTMCs). However, mortality has not changed, suggesting overdiagnosis and overtreatment. Prospective clinical trials of active surveillance for low-risk PTMC (T1aN0M0) have been conducted in two Japanese institutions since the 1990s. Based on the favorable outcomes of these trials, active surveillance has been gradually adopted worldwide. A task force on the management of PTMC in adults organized by the Japan Thyroid Association therefore conducted a systematic review and has produced the present position paper based on the scientific evidence concerning active surveillance. This paper indicates evidence for the increased incidence of PTMC, favorable surgical outcomes for low-risk PTMC, recommended criteria for diagnosis using fine needle aspiration cytology, and evaluation of lymph node metastasis (LNM), extrathyroidal extension (ETE) and distant metastasis. Active surveillance has also been reported with a low incidence of disease progression and no subsequent recurrence or adverse events on survival if conversion surgery was performed at a slightly advanced stage. Active surveillance is a safe and valid strategy for PTMC, because it might preserve physical quality of life and reduce 10-year medical costs. However, some points should be noted when performing active surveillance. Immediate surgery is needed for PTMC showing high-risk features, such as clinical LNM, ETE or distant metastasis. Active surveillance should be performed under an appropriate medical team and should be continued for life.

Objective: To investigate the difference of prognostic factors and recurrence rates between papillary thyroid microcarcinoma (PTMC) and lager papillary thyroid carcinoma (PTC) and analyze the clinical pathological characteristics of PTMC suitable for surgery. Methods: A retrospective analysis on the clinicopathological features, expression level of of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600E gene mutation and pigment epithelium-derived factor (PEDF), and postoperative follow-up results of the 251 PTC patients who underwent surgical treatment from October 2011 to October 2013, including 169 cases with PTMC and 82 with lager PTC (Tumor diameter>1 cm). Results: The BRAF V600E mutation rates of PTMC and lager PTC patients are 65.1%(110/169)and 78.0% (64/82) respectively, and the difference is statistically significant (P<0.05). The prevalence of extrathyroidal invasion (7.1%) and lymph nodes metastasis (27.2%) of the patients with PTMC were significantly lower than those of the patients with larger PTC (15.9% and 46.3%, respectively)(P<0.01). The follow-up durations for PTMC and lager PTC were (45.6±3.6) months and (45.0±3.4) months, respectively (P>0.05). There was no statistic significance for the difference in age, gender, coexistent hashimoto's thyroiditis, PEDF expression, and recurrence rate between the patients with PTMC and with larger PTC (P>0.05). The recurrence rate of the patients who have the high risk factors of PTMC was 1.6%(2/122)and that of larger PTC was 4.9% (4/82). Conclusions: Extrathyroid invasion, lymph node metastases and BRAF V600E gene mutation are the high risk factors of recurrent PTMC. The same treatment strategy should be considered for PTMC with coexistent high risk factors as that for larger PTC. For PTMC with BRAF V600E gene mutation, earlier surgical treatment is suggested. PTMC patients with BRAF V600E gene mutation and high cell subtype are suggested to undergo total thyroidectomy for the first operation in order to reduce the potential risk of recurrence.

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.

BackgroundOvertreatment of papillary thyroid microcarcinoma (PTMC) has become a common concern. This study aimed to compare clinicopathological features between PTMC and papillary thyroid carcinoma (PTC) and to explore whether surgery can confer significant survival benefits in all patients with PTC or PTMC.MethodsData of 145,951 patients with PTC registered in Surveillance, Epidemiology, and End Results (SEER) database and 8,751 patients with PTC in our institution were retrospectively collected. Patients with tumors less than 10 mm in diameter were classified as PTMC cohort and the rest as PTC cohort. Clinicopathological features between PTMC and PTC were compared on the basis of SEER cohort and validated with institutional data. Survival analysis was conducted to explore the effect of surgery on the prognosis of patients. To minimize potential confounders and selection bias, we performed propensity score matching (PSM) analysis to match more comparable cohorts.ResultsCompared with PTC, PTMC exhibited the following characteristics: more common in women and whites, older age at diagnosis, lower proportion of follicular variants, intraglandular dissemination, extraglandular and capsular invasion, higher proportion of multifocality, fewer lymph node and distant metastases, and higher cancer-specific survival (CSS) and overall survival (OS) (all p-value < 0.05). Regarding treatment, patients with PTMC received a lower proportion of radiotherapy, chemotherapy, and total thyroidectomy but a higher proportion of lobectomy and/or isthmectomy. There was no significant difference in CSS for patients with PTMC at stage T1N0M0 with or without surgery (P = 0.36).ConclusionGenerally, PTMC showed higher biological indolence than PTC, which meant a higher survival rate for patients in both OS and CSS. For patients with PTMC at staged T1N0M0, active surveillance (AS) may be a potentially feasible management strategy. However, the maintenance of good medical compliance and the management of psychological burden cannot be ignored for patients included in AS.

BackgroundDistant metastasis from papillary thyroid microcarcinoma (PTMC) is rare. Here we report a case of PTMC with multiple lung metastases.Case presentationA 64-year-old man presented to our hospital with abdominal pain. Computed tomography incidentally revealed multiple lung nodules. The lung tumor was histologically diagnosed as metastasis of papillary thyroid carcinoma (PTC) by core needle biopsy via thoracoscopy. The patient was referred to our department for further examination. Neck ultrasonography revealed a 0.9 cm hypoechoic nodule in the right lobe of the thyroid gland, which was diagnosed as PTC by fine-needle aspiration cytology. Subsequently, total thyroidectomy was performed, followed by radioiodine therapy. Iodine-131 (131-I) scintigraphy showed a strong accumulation in the lung metastasis. The patient presented no evidence of progression of lung metastasis for 25 months after the operation.ConclusionsLymph node metastasis or extraglandular extension has been reported in the few published cases of metastatic PTMC, including the present case, and the average age of these cases was 58.8 ± 12.0 years. Although active surveillance without surgical resection is expected to become a standard of care for PTMC, this case indicates that a subset of PTMC patients with risk factors may develop distant metastases. Hence, careful preoperative screening is required to avoid complications associated with completion thyroidectomy.

Background: Active surveillance (AS) of papillary thyroid microcarcinomas (PTMC) is emerging as an alternative to immediate surgery. While thermal ablation has also shown promise for low-risk PTMC, it has not been prospectively studied in patients appropriate for AS. This study aimed to evaluate the efficacy and safety of ultrasound (US)-guided radiofrequency ablation (RFA) for tumor control and quality of life (QoL) management in patients with PTMC who favored AS over immediate surgery. Methods: This prospective clinical trial was conducted at a single tertiary referral hospital from 2018 to 2021. Of 227 adult patients aged ≤60 years with low-risk unifocal PTMC favoring AS over immediate surgery, 100 patients underwent RFA for their management. The primary endpoint was the disease progression rate, and secondary endpoints were technical success, volume reduction rate (VRR), complication rates, and QoL. Results: The median age of the study population was 42 years (range, 27-59 years), and 83% (83/100, [CI: 66.1-100]) were female. The median follow-up was 30 months (range, 12-56 months). All 100 patients underwent RFA with technical success. Most of the ablation zones showed continuous volume reduction, and 95.9% (94/98, [CI: 77.5-100.0]) showed complete disappearance at the last follow-up. The median VRR was 100.0% at 1-year follow-up and persisted throughout the last follow-up. The cumulative disease progression rate among 98 patients who underwent at least 1-year follow-up was 3.1% (3/98, [CI: 0.6-9.0]); one patient had lymph node metastasis (treated with surgery), and two patients had new PTMC (1 treated with RFA, 1 ongoing AS). Major complications were not observed. Psychological (baseline vs. last follow-up, 7.3 vs. 8.0, p = 0.002) and social (8.0 vs. 8.7, p = 0.005) QoL scores significantly improved during follow-up without compromising physical QoL (8.6 vs. 8.5, p = 0.99). Conclusions: RFA can be a reasonable strategy for effectively and safely controlling tumors and improving QoL in non-elderly patients with low-risk PTMC appropriate for AS. Clinical Trial registration: This trial is registered with ClinicalTrials.gov: NCT03432299.

BackgroundDistant metastasis is extremely rare for papillary thyroid microcarcinoma (PTMC) without lymph node metastasis or extrathyroidal extension, for which active surveillance (AS) is indicated. The evaluation of distant metastases in low-risk PTMC is controversial. A case of PTMC in which AS would have been performed if chest CT and lung surgery had not been performed is reported.Case presentationThe patient was a 71-year-old woman undergoing follow-up in the Department of Thoracic Surgery at our hospital for multiple frosted glass shadows in both lung fields for one and a half years. To make a definitive diagnosis, thoracoscopic right middle lobectomy and left upper partial lobectomy were performed 4 and 6 months earlier, respectively. In both resected specimens, lung adenocarcinoma and small metastasis of papillary thyroid carcinoma (PTC) were found. The patient was transferred to our department for a thorough examination for PTC. Ultrasonography was performed to search for the primary lesion, and it showed an irregular hypoechoic mass of 4 mm and 6 mm in the middle of the right lobe of the thyroid gland. The patient was diagnosed with PTC. Its clinical stage was T1a (m) N0 M1 (stage IVC). Total thyroidectomy and prophylactic central node dissection were performed. The pathological diagnosis was PTC (typical type) pT1a (m) N0. Postoperatively, she received radioactive iodine therapy.ConclusionsWe experienced an extremely rare case and struggled to determine a treatment plan. We might be aware that lung metastases could develop in low-risk PTMC.

Background: The Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) started in June 2016. As a follow-up study of comparing the quality of life (QoL) of the active surveillance (AS) and immediate surgery (OP) groups at 8 months (9.3±4.8 and 7.1±4.2 months, respectively), here we aimed to compare the QoL between the AS and OP groups after 18 months (22.8±4.0 and 22.3±4.3 months, respectively) of follow-up.Methods: QoL of 108 participants who chose AS, 101 who underwent OP, twelve who changed from AS to OP was evaluated using a thyroid‐specific QoL questionnaire at diagnosis and during follow‐up (median 23 months).Results: The mean ages of the participants in the AS and OP groups were 47.7±11.0 and 45.1±10.0 years (p=0.075), respectively. At baseline, better physical (8.2±1.4 vs. 7.6±1.8, p=0.032), psychological (7.4±1.2 vs. 6.7±1.6, p=0.010), and total health (7.4±1.0 vs. 6.7±1.3, p=0.005) were observed in the AS group than in the OP group. After a mean follow up of 22.7±4.2 months, better physical (8.1±1.5 vs. 7.4±1.7, p=0.008), psychological (7.7±1.3 vs. 7.0±1.5, p=0.002), and total health (7.5±1.2 vs. 6.8±1.3, p=0.001) were observed in the AS group than in the OP group, whereas spiritual health was comparable between the two groups: compared with the AS group, the OP group experienced more alterations in appetite, sleep, menstrual cycle, voice, motor skill, weight, appearance, cold or heat tolerance, and body swelling. Furthermore, better QOL scores were observed in the AS group in self-concept, personal relationships, sexual life, work motivation, productivity and quality of work, feeling of isolation, driving, doing household chores, preparing meals and doing leisure activities after long term follow up.Conclusion: Patients who underwent AS had better QOL even after long term follow up. Low risk papillary thyroid microcarcinomas do not influence survival, however surgery related deterioration of QOL lasted long and did not improve even in late post-operative stages when patients were fully recovered from surgery.Keywords: Quality of life; papillary thyroid microcarcinoma; active surveillance; immediate surgery

Objective: To investigate the rationality of management of active surveillance for papillary thyroid microcarcinoma (PTMC) and the main indications for active surveillance for PTMC. Methods: In this study, two criteria were used to evaluate patients with PTMC: low-risk PTMC conditions defined by Kuma hospital and Chinese Association of Thyroid Oncology (CATO) consensus on PTMC management of active surveillance. The patients had received surgical treatment. Clinicopathological characteristics and prognosis of the patients in different groups were compared. Results: A total of 778 patients were enrolled in the study, 565 (72.6%) of them met Kuma screening criteria and only 112 (14.4%) met CATO screening criteria. Kuma low-risk subgroup had lower incidence of cervical lymph node metastasis than Kuma high-risk PTMC subgroup(30.6% vs 47.9%, P<0.05). There were significant differences in multifocal lesions(6.3% vs 16.4%), extrathyroidal extension (1.8% vs 7.5%) and cervical lymph node metastasis(19.6% vs 38.0%) between low-risk and high-risk CATO PTMC subgroups. Patients in the CATO low-risk PTMC subgroup had lower recurrence and longer disease-free survival (DFS) than those in the CATO high-risk PTMC subgroup. But there was no significant difference in recurrence or DFS between Kuma low-risk and high-risk Kuma PTMC subgroups.The Chi-square test of Fisher's exact probabilities test was used to compare clinicopathological characteristics of patients between different groups.Rates of disease-free survival were calculated using the Kaplan-Meier method. Conclusion: CATO screening criteria is relatively strict and may be more suitable for Chinese patients with active surveillance for PTMC.

Objective To explore risk factors of recurrence in papillary thyroid microcarcinomas(PTMC)and papillary thyroid carcinomas with 1-2 cm diameter. Methods From January, 2008 to December, 2010 in PLA General Hospital, 323 eligible patients received first surgery and diagnosed pathologically with papillary thyroid cancer≤2 cm were analyzed retrospectively. According to rumor size, patients were divided into PTMC and PTC of 1-2 cm, which were investigated recurrence factors. Results Finally we indentified 320 PTC≤2 cm, including 218(68.1%)PTMC and 102(31.9%)PTC of 1-2 cm with a median follow-up time of 72.5(55-90)months.32 cases(10%)of patients relapse, includig 22 cases(10%)in PTMC and 10 cases(9.8%)in PTC of 1-2 cm. In the clinical characteristics analyses of PTC≤2 cm, the PTC of 1-2 cm was different from PTMC in age, lymph node metastasis and TNM stage. The univariate analysis showed that tumor location and lymph node metastasis influenced recurrence of PTMC and PTC of 1-2 cm, while tumor foci and extrathytoidal extension were risk factors of recurrence in PTMC but not in PTC of 1-2 cm. Lymph node metastasis was independent factor which influenced the recurrence of PTMC and PT C of 1-2 cm according to COX multivariate analysis. Conclusion Disease recurrence did not differ significantly between the PTMC and PTC of 1-2 cm and lymph node metastasis was an independent recurrence factor. (Chin J Endocrinol Metab, 2016, 32: 391-394) Key words: Papillary thyroid carcinomas; Recurrence