Cost-effectiveness of active surveillance versus early surgery for thyroid micropapillary carcinoma based on diagnostic and treatment norms in China.

BackgroundRecently, active surveillance (AS) has been introduced as an alternative to early surgery (ES) for the management of papillary thyroid microcarcinoma (PTMC), because of its indolent features and low mortality. However, its cost effects have not been determined and the findings of current studies differ, according to each country’s medical system.MethodsA Markov model was constructed to compare the cost-effectiveness of AS and ES, based on a reference case of a 40-year-old patient diagnosed with PTMC. Costs and transition probabilities were derived from previous clinical studies in Korean populations, and the incremental cost-effectiveness ratio (ICER) and net monetary benefit (NMB) were calculated. The willingness-to-pay (WTP) threshold was set at USD 100,000 per quality-adjusted life year (QALY) gained. Sensitivity analyses were conducted to address the uncertainties in the model’s variables.ResultsFrom the base scenario, the cumulative costs and effectiveness were both higher in ES than AS. The ICER for ES, compared with AS, was USD 6,619.86/QALY, lower than the set WTP. The NMB difference between AS and ES increased across the stages (USD 5,980 at the first stage and USD 159,667 at the last stage). The ICER increased along with decreasing age and increasing cost of surgery. The higher the ES utility score and the lower that of AS, the more cost-effective ES, with WTP set at USD 30,000.ConclusionIn the current Korean medical system, ES is more cost-effective than AS. ES is more cost-effective as it is diagnosed at young age and followed-up for a long time.

Introduction: Micropapillary thyroid carcinoma was emerging as an epidemic disease worldwide. Due to its unaggressiveness and slow-growing feature, either doing active surveillance or surgical approach were controversial for its management. This meta analysis aimed to determine the pooled proportion outcomes of doing active surveillance and surgery in micropapillary thyroid carcinoma. Methods: This meta analysis of the results in doing active surveillance and surgical approach for micropapillary thyroid carcinoma, designed followed the PRISMA guidelines. Relevant studies were obtained from Medline (2008-2018) and SCOPUS (2008-2018) in the last 20 years. The scope of data collection is about the author, year of study, and number of subjects. The parameter of this study was pooled proportion. Data were analyzed by MedCalc 13.5 and the significance limit was 0.05. Results: The pooled proportion of cases of surgery conversion, increasing tumor size more than 3 cm, and the presence of lymph node metastases during active surveillance of micropapillary thyroid carcinoma were 14.996; 6.125%; and 4.988%, respectively. The pooled proportion of cases of recurrence and lymph node metastases after surgery of micropapillary thyroid carcinoma were 3.539% and 14.071%, respectively. Discussion: In this study, it was showed that result was favorable in doing active surveillance. The rate of lymph node metastases were comparable in non and interventional group. However, this approach should be considered cases by cases. Many individual factors like age, gender, and comorbidities should be considered. Conclusion: Active surveillance was a safe and considered approach for micropapillary thyroid carcinoma. However, some risk factor should be considered for surveillance exclusion.

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.

Papillary thyroid microcarcinomas carry an excellent prognosis, making patient preferences and cost-effectiveness important determinants of treatment selection. To conduct cost-effectiveness analyses, quality-adjusted life year weights for papillary thyroid microcarcinoma treatments must be derived. Our objective was to estimate the quality-adjusted life year weights of common papillary thyroid microcarcinoma treatment scenarios. This study used 10 previously published papillary thyroid microcarcinoma clinical vignettes describing active surveillance, radiofrequency ablation, partial thyroidectomy, and total thyroidectomy, along with potential complications (progression, vocal cord palsy, hypocalcemia). Quality-adjusted life year weights were derived using a time trade-off instrument administered to thyroid cancer survivors. Quality-adjusted life year weights were compared using within-subjects repeated measures analysis of variance and paired Wilcoxon rank-sum tests. The cohort was powered to detect a minimal important difference with an effect size of 0.5 (ie, 0.04 quality-adjusted life year). Data from 101 thyroid cancer survivors were collected. Median quality-adjusted life year weights for uncomplicated treatment scenarios ranged from 0.975 to 0.992 and were not significantly different between treatments (P = .15). Treatment complications resulted in significantly lower quality-adjusted life year weights across all treatment strategies (P < .01) except active surveillance (P = .72). Quality-adjusted life year weights were comparable between the uncomplicated versions all 4 treatment pathways, suggesting that patient treatment preferences for papillary thyroid microcarcinoma are driven by aversion to treatment complications, rather than an inclination toward the experience of the treatments themselves. These quality-adjusted life year weights may be readily incorporated into value assessments for papillary thyroid microcarcinoma treatments.

Thyroid lobectomy as a cost-effective approach in low-risk papillary thyroid cancer versus active surveillance

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.

Papillary thyroid microcarcinoma (PTMC) is generally an indolent disease and active surveillance is conducted for low-risk cases. This study was carried out to clarify the pathological characteristics of PTMC cases that exhibited enlarged nodules or nodal metastasis during the surveillance period. A total of 188 PTMC cases that underwent surgery after active surveillance for ≥ 1 year were examined. Ki-67 labeling indices of > 5% and > 10% were detected in 50.0% and 22.2% of enlarged cases, respectively, values that were significantly higher than those in non-enlarged cases. Intraglandular dissemination and psammoma bodies in normal thyroid tissue were associated with new occurrence of nodal metastasis. Ultrasonographic macrocalcification and follicular variants were observed in 13.8% and 10.6% of non-enlarged cases, respectively, but not in enlarged or nodal metastatic cases. Intraglandular dissemination and psammoma bodies were ultrasonographically detected in 50.0% and 40.0% of cases, which was confirmed by microscopy. Thus, high Ki-67 labeling index, intraglandular metastasis, and psammoma bodies in normal thyroid tissue are indicators of progressive PTMC, and may be identified cytologically or ultrasonographically. In PTMC cases with ultrasonographic macrocalcification, active surveillance can be proactively implemented.

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.

The growing detection of papillary thyroid microcarcinomas (PTMCs) is paralleled by an increase in surgical procedures. Due to the frequent indolent nature, cost, and risk of surgery, active surveillance (AS) and ultrasound-guided minimally invasive treatments (MITs) are in suitable cases of incidental PTMC proposed as alternatives to thyroidectomy. Surgery and radioiodine are the established treatments for relapsing cervical differentiated thyroid carcinoma (DTC) metastases. But radioiodine refractoriness, risk of surgical complications, adverse influence on quality of life, or declining repeat surgery have led to AS and MIT being considered as alternatives for slow-growing DTC nodal metastases. Also, for distant radioiodine-refractory metastases not amenable to surgery, MIT is proposed as part of a multimodality therapeutic approach. The European Thyroid Association and the Cardiovascular and Interventional Radiological Society of Europe commissioned these guidelines for the appropriate use of MIT. Based on a systematic PubMed search, an evidence-based approach was applied, and both knowledge and practical experience of the panelists were incorporated to develop the manuscript and the specific recommendations. We recommend that when weighing between surgery, radioiodine, AS, or MIT for DTC, a multidisciplinary team including members with expertise in interventional radiology assess the demographic, clinical, histological, and imaging characteristics for appropriate selection of patients eligible for MIT. Consider TA in low-risk PTMC patients who are at surgical risk, have short life expectancy, relevant comorbidities, or are unwilling to undergo surgery or AS. As laser ablation, radiofrequency ablation, and microwave ablation are similarly safe and effective thermal ablation (TA) techniques, the choice should be based on the specific competences and resources of the centers. Use of ethanol ablation and high-intensity focused ultrasound is not recommended for PTMC treatment. Consider MIT as an alternative to surgical neck dissection in patients with radioiodine refractory cervical recurrences who are at surgical risk or decline further surgery. Factors that favor MIT are previous neck dissection, presence of surgical complications, small size metastases, and <4 involved latero-cervical lymph nodes. Consider TA among treatment options in patients with unresectable oligometastatic or oligoprogressive distant metastases to achieve local tumor control or pain palliation. Consider TA, in combination with bone consolidation and external beam radiation therapy, as a treatment option for painful bone metastases not amenable to other established treatments.

In 1993, active surveillance of low-risk papillary thyroid microcarcinomas (PTMCs) started in Kuma Hospital, Kobe, Japan. It has spread globally after the publishing of American Thyroid Association (ATA) guidelines. During our hospital's active surveillance program, few patients (8.0%) showed tumor size enlargement ≥3 mm or the new appearance of node metastasis (3.8%) at 10-year follow-up. Conversion surgery was recommended for patients with disease progression. To date, no patients showed significant recurrence or metastasis or died with thyroid carcinoma when patients underwent active surveillance or after surgery due to PTMC progression. Unlike clinical papillary thyroid carcinoma (PTC), elderly patients' PTMCs were less progressive compared to those of young and middle-aged patients, indicating that elderly patients are strong candidates for the active surveillance of their PTMC. Although young patients' PTMCs are the most progressive, >50% and >75% of patients in their 20s and 30s would avoid conversion surgical treatment in their lifetime, respectively (according to estimated lifetime probability), indicating that such young patients are still candidates for active surveillance. It can thus be concluded that active surveillance is appropriate to be first management for PTMCs, based on the accumulation of favorable outcomes of PTMC patients who have undergone active surveillance, as well as the lower incidences of unfavorable events and lower medical cost than immediate surgery.

Introduction: In this study, we aimed to investigate the importance of some distinctive morphological parameters in predicting the extrathyroidal extension, as marker of aggressiveness, in a series of papillary thyroid microcarcinoma (PTMC) cases. Material and methods: All consecutive PTMC cases, sized ≥ 5mm, registered at the Department of Pathology, Tîrgu-Mureș Emergency County Hospital from January 2002 to December 2013 were re-evaluated. The following histological features were noted: the multifocality, the extrathyroidal extension, the histologic variant, the tumor’s border (well circumscribed versus infiltrative), the PTC nuclear features (well developed versus subtle), the tumor associated stromal reaction (fibrosis/desmoplasia/sclerosis versus none of these changes), the presence of “plump pink” cells, psammoma bodies, intratumoral lymphocytic infiltrate, cystic change, back-to-back arrangement, intratumoral multinucleated giant cells and lymph node involvement. Results: Our study included 72 PTMC cases, summing up to a total of 80 PTMC foci. We have shown that extrathyroidal extension is significantly associated with the presence of “plump pink”cells (p=0.0019), well developed nuclear features of PTC (p=0.018) and tumor associated stromal reaction (fibrosis/dezmoplazia/sclerosis) (p&lt;0.0001). Other parameters were more prevalent among PTMC foci with extrathyroidal extension, but did not reach statistical significance. Conclusion: Our results pointed out the importance of a distinct set of morphological microscopical parameters, predictive for extrathyroidal extension in PTMC cases (“plump pink” cells, well developed PTC nuclear features, tumor associated stromal reaction, infiltrative tumor borders and conventional PTC histology). All these parameters are important to be mentioned in the histopathological reports, as they might be associated with a more aggressive biological behaviour.

Papillary thyroid microcarcinoma (PTMC) has indolent features and low mortality. Recently, active surveillance (AS) instead of early surgery (ES) has been introduced as one treatment option but economical preference has not been established. The study objective was to systemically review the literature relating to cost-effectiveness of AS compared to ES for PTMC. Keywords were selected through PICO (Population, Intervention, Comparison, and Outcomes) tools. The search was conducted using PubMed, Cochrane, EMBASE, and Elsevier databases. Papers that had irrelevant titles were written in foreign languages, or had no original results were excluded. Out of the 62 papers extracted, five relevant to the subject matter of this study were identified. Three papers made their own decision models and proceeded with cost-effectiveness analysis (CEA), but the remaining two simply compared costs rather than cost-effectiveness. In terms of cost-effectiveness, three papers preferred AS, one preferred ES, and one preferred neither. The major differences in the CEA might arise from variations in each country’s medical insurance system, the utility score systems, and decision models used. In subgroup analysis, two papers preferred AS to ES for patients at a younger age at diagnosis in terms of cost-effectiveness as well as tumor biological characteristics. Although AS has been generally more cost-effective than ES in previous publications, younger age at diagnosis could be one factor contributing to preference for ES. The CEA of prospective cohorts based on the decision model and utility score for thyroid cancer should be undertaken to confirm the cost-effectiveness of AS.

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

Overdiagnosis of papillary thyroid microcarcinoma (PTMC) is prevalent, and effective management of PTMC is an important matter. The high incidence and low mortality rate of papillary thyroid carcinoma (PTC) justify the preference for active surveillance (AS) over immediate surgery (IS), particularly in cases of low-risk PTMC. Japan began AS in the 1990s as an alternative surgical option for PTMC and it has shown promising results. The safety and efficacy of AS management in PTMC have been verified. However, AS may not be suitable for all PTMC cases. How to find the balance between the decision-making of AS and IS requires careful consideration. Therefore, we collected and analyzed the relevant evidence on the clinical strategies for PTC and discussed AS and IS from the perspectives of health, economic, and psychological aspects, to help clinicians in choosing a more appropriate clinical strategy for PTC.

INTRODUCTION The current recommended management strategy for small, asymptomatic unruptured anterior circulation aneurysms (UIAs) is active surveillance utilizing serial magnetic resonance angiography (MRA). Our objective was to determine the cost-effectiveness of active surveillance via MRA, immediate surgery, and watchful waiting for small UIAs. METHODS We developed a Markov cost-effectiveness model simulating a cohort of patients with small (&lt;7 mm) UIAs diagnosed at age 50-yr who were treated with active surveillance via MRA, immediate surgery, or watchful waiting. Model inputs (eg risk of aneurysm growth, rupture rate, treatment complications, etc) were abstracted from peer-reviewed literature. Outcomes were quality-adjusted life-years (QALY), lifetime medical costs (2015 US$), and incremental cost-effectiveness ratios (ICER). Cost-effectiveness analysis as well as deterministic and probabilistic sensitivity analyses were performed. Willingness to pay (WTP) threshold was $100,000/QALY. RESULTS At a WTP of $100,000/QALY, immediate surgical treatment was the most cost-effective management strategy for small UIAs; ICER of $43,880 relative to active surveillance. Sensitivity analyses demonstrated immediate surgery was the preferred strategy if rupture rate was &gt;0.1%/yr and if diagnosis age was &lt;70 yr. Active surveillance became the preferred strategy if surgical complication risk was &gt;11% and if diagnosis age was &gt;70-yr. MRA surveillance interval did not significantly impact cost-effectiveness (surveillance frequency range 6 mo-10 yr). Probabilistic sensitivity analysis demonstrated that at a WTP of $100,000/QALY immediate surgery was the most cost-effective strategy in 64% of iterations (compared to active surveillance in 34%, and watchful waiting in 1.4%). CONCLUSION Immediate surgical treatment is a reasonable and cost-effective strategy for initial management of small UIAs. The cost-effectiveness of immediate surgery is highly sensitive to age at diagnosis, rupture rate, and probability of surgical complication. As there are wide published ranges for rates of rupture and surgical complications, individual lesion characteristics and surgeon-specific complication metrics should be considered in counseling patients.