ThyroSeq v2 Testing: Impact on Cytologic Diagnosis, Management, and Cost of Care in Patients with Thyroid Nodule.

Background: Novel molecular tests (MTs), such as ThyroSeq, may improve the management of thyroid nodules with indeterminate cytologic diagnoses; however, the impact of these tests on cost and outcome of management is unknown. Here, we evaluated the impact of ThyroSeq testing on the cytopathologic diagnosis, management, and cost of care in patients with thyroid nodules. Methods: In a retrospective study, using actual patient cohorts, the outcome and cost of management of patients with thyroid nodules seen before the introduction of ThyroSeq v2 at our institution (standard of care [StC] cohort) were compared with those seen after the introduction of this test (MT cohort). Results: A total of 773 consecutive patients entered the study (393 StC, 380 MT). The incidence of cytologically benign nodules decreased from 71.0% (StC) to 53.2% (MT) and those of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) and follicular neoplasm/suspicious for follicular neoplasm (FN/SFN) increased from 8.9% (StC) to 21.3% (MT) and from 3.1% (StC) to 6.3% (MT), respectively. The overall rate of surgery did not change significantly (23.4% in StC vs. 23.2% in MT). Among patients who underwent surgery, the rate of overtreatment (surgeries performed on histologic benign nodules without clinical indication: compressive symptoms, hyperthyroidism resistant to medication, and nodule size >4 cm) slightly decreased from 18.8% (StC) to 16.7% (MT). The rate of malignancy decreased from 45.5% (StC) to 37.9% (MT) in AUS/FLUS and increased from 40.0% to 53.8% in FN/SFN. However, the overall rate of malignancy remained equal (47.8% in StC vs. 47.7% in MT). The average cost of care per patient in the AUS/FLUS and FN/SFN categories increased from $6,566 (StC) to $8,444 (MT) and from $9,313 (StC) to $10,253 (MT), respectively. Similarly, the overall average cost of care of a patient who underwent thyroid fine-needle aspiration increased from $3,088 (StC) to $4,282 (MT). Finally, the average cost per thyroid cancer detected increased from $26,312 (StC) to $38,746 (MT). Conclusions: Introduction of ThyroSeq v2 resulted in a shift toward indeterminate cytology results. The institutional rate of surgery, overtreatment, and malignancy did not change significantly. Lack of decrease in the rate of surgery along with the additional cost of ThyroSeq v2 increased the overall cost of care of patients including those with indeterminate cytology results.

Cost-effectiveness of fine-needle aspiration cytology (FNAC) and watchful observation for incidental thyroid nodules.

OBJECTIVES: A trial-based comparison of the use of resources, costs and health utility outcomes of fine-needle aspiration cytology (FNAC), and watchful observation for incidental small (< 2 cm) thyroid nodules was performed using data from the randomized controlled trial (RCT). METHODS: Using data from 314 patients, healthcare-related use of resources, costs, health utility, and quality-adjusted life years (QALYs) were estimated at 12 months after first presentation of incidental thyroid nodule(s) on an intention-to-treat basis with adjustment for covariates. Uncertainty about the incremental cost-effectiveness ratio for FNAC versus watchful management at 12 months of follow-up was incorporated using bootstrapping. Multiple imputation methods were used to deal with missing data. RESULTS: FNAC management was associated with greater use of healthcare resources and mean direct healthcare costs per patient (US$542.47 vs US$411.55). Lower mean 12-month QALYs per patient in FNAC was observed in comparison to watchful observation (0.752 versus 0.758). The probability that FNAC management was cost-effective compared with watchful management at a willingness-to-pay threshold of US50,000 per QALY gained was 26.5%. CONCLUSION: Based on 12-month data from RCT, watchful observation appeared cost-saving compared to FNAC in patients with incidental thyroid nodules that have a low-suspicion sonographic pattern and measure between 1.0 and 2.0 cm from healthcare provider perspective. CLINICALTRIALS. GOV IDENTIFIER: NCT02398721.

Molecular Testing Versus Diagnostic Lobectomy in Bethesda III/IV Thyroid Nodules: A Cost-Effectiveness Analysis.

Background: Molecular tests (MT) using gene expression and/or mutational analysis have been developed to reduce the need for diagnostic surgery for indeterminate (Bethesda III/IV) thyroid nodules. Prior cost-effectiveness studies have shown mixed results but none has included the recent and more comprehensive versions of the two commonly utilized MT. The aim of this study is to compare the cost-effectiveness of diagnostic lobectomy (DL), the Afirma Gene Sequencing Classifier (GSC), and ThyroSeq version 3 (TSv3). Methods: A decision tree from the payer perspective was created using a base case of a 40-year-old euthyroid woman with a solitary 2 cm Bethesda III or IV thyroid nodule. In this model, all patients in the DL arm had lobectomy, which was also performed for patients with positive MT, while those with negative MT underwent 20 years of surveillance. The outcome was a correct diagnosis, defined as malignant histology after DL or 20 years of nodule stability after negative MT. Costs were obtained from the Centers for Medicare & Medicaid Services (CMS) data and existing literature, and probabilities were obtained from the literature. Sensitivity analysis was performed for costs, pretest probability of malignancy, and performance parameters. Results: The cost per correct diagnosis was $14,277 for TSv3, $17,873 for GSC, and $38,408 for DL. TSv3 was preferred over both GSC and DL. One-way sensitivity analysis between TSv3 and GSC demonstrated that the results were robust to variations in cost, cancer prevalence, and length of surveillance. In the two-way sensitivity analysis, TSv3 was preferred over GSC at all considered test costs, and in probabilistic sensitivity analysis, TSv3 was the preferred management strategy in 68.5% of cases. Conclusions: In hypothetical modeling to determine whether surgery versus MT is optimal for indeterminate (Bethesda III/IV) nodules, either of the major MT was considerably more cost-effective than DL, although TSv3 was more likely to be cost-effective than GSC. Use of either MT adjunct should be strongly considered in the absence of other indications for thyroidectomy.

Use of a low-cost telecytopathology method for remote assessment of thyroid FNAs.

BACKGROUND: Rapid on-site evaluation is a great tool for optimizing the adequacy and quality of cytologic samples. The objective of the current study was to analyze a low-cost telecytopathology method for the remote assessment of thyroid fine-needle aspiration biopsies (FNABs), with comparison of the primarily rendered adequacy and diagnosis with the final conventional analysis. METHODS: Material collected from thyroid FNABs was immediately smeared onto glass slides and stained with Diff-Quik. A conventional microscope attached to a smart device was operated on-site by either a medical student or a pathology resident for Wi-Fi transmission of the images by Skype. The cytopathologist would remotely guide the screening of the slides, zooming in and out of areas of interest. Remote assessment included an analysis of material adequacy and a preliminary diagnosis. The quality of the transmission and the number of slides also were recorded. After a washout period of 3 weeks, final diagnosis and adequacy were assigned by conventional microscopy. RESULTS: The final agreement rate for adequacy between remote and conventional analysis was 90.5%. For diagnosis, the final agreement rate was 83.3%. The diagnosis agreement rate varied, depending on the quality of transmission: there was 88% agreement when the quality was excellent, 77.8% agreement when it was good, and 62.5% agreement when it was poor. CONCLUSIONS: Low-cost telecytopathology is an efficient method for the remote assessment of thyroid FNAB adequacy and diagnosis. The wide use of such technology in low-resource or remote centers may have a positive impact on the number of adequate or satisfactory samples, optimizing the management of patients who have thyroid nodules.

Cost effectiveness of immediate biopsy versus surveillance of intermediate-suspicion thyroid nodules.

BACKGROUND: In an effort to reduce overdiagnosis of low-risk thyroid cancer, recent clinical guidelines increased the size-based biopsy thresholds for thyroid nodules. The cost-effectiveness of these guidelines is largely unknown. We hypothesized that ultrasound surveillance in lieu of immediate fine needle aspiration biopsy would be cost effective for a 1.0 cm thyroid nodule with American Thyroid Association Intermediate Suspicion sonographic features. METHODS: A Markov transition-state model was constructed to compare immediate fine needle aspiration versus ultrasound surveillance. Univariate and multivariate sensitivity analyses were used to examine the uncertainty of cost, probability, and utility estimates in the model. RESULTS: Ultrasound surveillance was $1,829 less costly and 0.016 quality-adjusted life years more effective than immediate fine needle aspiration. Immediate fine needle aspiration became cost effective when the probability of malignancy increased from 15% to 84% or the cost of ultrasound increased from $129 to $793. Immediate fine needle aspiration was cost-effective if the quality adjustment factor for observation following a benign fine needle aspiration result exceeded the quality adjustment factor for observation without a biopsy. CONCLUSION: Ultrasound surveillance is more cost-effective than immediate fine needle aspiration for 1.0 cm thyroid nodules with an intermediate-suspicion sonographic pattern. Additional investigation of health-related quality of life in patients undergoing fine needle aspiration or surveillance is necessary.

Cost-effectiveness of lobectomy versus genetic testing (Afirma®) for indeterminate thyroid nodules: Considering the costs of surveillance.

BACKGROUND: We evaluated whether diagnostic thyroidectomy for indeterminate thyroid nodules would be more cost-effective than genetic testing after including the costs of long-term surveillance. METHODS: We used a Markov decision model to estimate the cost-effectiveness of thyroid lobectomy versus genetic testing (Afirma®) for evaluation of indeterminate (Bethesda 3-4) thyroid nodules. The base case was a 40-year-old woman with a 1-cm indeterminate nodule. Probabilities and estimates of utilities were obtained from the literature. Cost estimates were based on Medicare reimbursements with a 3% discount rate for costs and quality-adjusted life-years. RESULTS: During a 5-year period after the diagnosis of indeterminate thyroid nodules, lobectomy was less costly and more effective than Afirma® (lobectomy: $6,100; 4.50 quality-adjusted life- years vs Afirma®: $9,400; 4.47 quality-adjusted life-years). Only in 253 of 10,000 simulations (2.5%) did Afirma® show a net benefit at a cost-effectiveness threshold of $100,000 per quality- adjusted life-years. There was only a 0.3% probability of Afirma® being cost saving and a 14.9% probability of improving quality-adjusted life-years. CONCLUSIONS: Our base case estimate suggests that diagnostic lobectomy dominates genetic testing as a strategy for ruling out malignancy of indeterminate thyroid nodules. These results, however, were highly sensitive to estimates of utilities after lobectomy and living under surveillance after Afirma®.

Cost-effectiveness of Gene Expression Classifier Testing of Indeterminate Thyroid Nodules Utilizing a Real Cohort Comparator.

Objective To predict the cost-effectiveness of implementing routine gene expression classifier testing for thyroid nodules with indeterminate fine-needle aspiration cytology, by utilizing a real cohort of patients as a comparator. Study Design Cost-effectiveness analysis of a retrospective cohort compared with a simulated cohort. Setting Tertiary academic medical center. Subjects and Methods We reviewed the records of all patients who underwent ultrasound-guided fine-needle aspiration from 2010 to 2014 at a tertiary academic medical center. All patients with Bethesda class III or IV cytopathology had the details of their management catalogued over the subsequent 2 years of care. These patients were assigned to the standard-of-care arm of the study. We compared the third-party payer costs of care and the proportion of patients who underwent surgery with a simulated cohort who underwent gene expression classifier testing after an initial indeterminate fine-needle aspiration (molecular test arm). Results The cost of managing 1 nodule over 2 years was $2399 higher (range, $397-$4399) for the molecular test group than the standard of care group. The molecular test group had a 13.1% decrease (base parameters; range, 0.73%-45.09%) in the number of patients undergoing surgery. Conclusion When applied to a real cohort of patients, routine gene expression classifier is predicted to reduce the number of patients undergoing surgery but will increase cost of care. Cost-effectiveness is heavily dependent on prevalence of malignancy and gene expression classifier specificity.

Cost comparison of initial lobectomy versus fine-needle aspiration for diagnostic workup of thyroid nodules in children.

BACKGROUND: Though uncommon in children, pediatric thyroid nodules carry a higher risk of malignancy than adult nodules. While fine-needle aspiration (FNA) has been well established as the initial diagnostic test in adults, it has been more slowly adopted in children. The purpose of this study was to examine the comparative cost of FNA versus initial diagnostic lobectomy (DL) in the pediatric patient with an ultrasound-confirmed thyroid nodule. METHODS: A decision tree model was created using an adolescent with an asymptomatic thyroid nodule as the reference case. Probabilities were defined based on review of the pediatric and adult literature. Costs were determined from previous literature and the publicly available Medicare physician fee schedule. Tornado plot and sensitivity analyses were performed to assess sources of cost variation. RESULTS: Using decision analysis, FNA was less costly than DL with an estimated cost of $2529 vs. $5680. Tornado analysis demonstrated that the probability of an initial indeterminate FNA result contributed most to cost variation. On sensitivity analysis, when probability of an indeterminate FNA result was increased to 35%, the maximum value found in the literature, FNA remained less costly. In Monte Carlo simulation set to 10,000 iterations, FNA was superior to DL in 74% of cases. CONCLUSIONS: In this theoretical model based on available literature and costs, FNA is less costly than DL for initial diagnostic workup of thyroid nodules in children. Securing resources to offer FNA in the work-up of thyroid nodules may be financially beneficial to hospitals and patients. LEVEL OF EVIDENCE: Level 1 cost effectiveness study - using reasonable costs and alternatives used in study with values obtained from many studies, study used multi-way sensitivity analysis.

Is TSH necessary for initial assessment of thyroid nodules?

OBJECTIVE: The use of thyrotropin (TSH) in the initial assessment of thyroid nodules is inefficient and leads to unnecessary assessment costs. We compared the total costs of thyroid nodule assessment with or without the use of TSH in the initial assessment. METHODS: A total of 1808 patients with thyroid nodules received TSH, fine-needle aspiration (FNA) and thyroid scintigraphy (TS) assessment, including 83 autonomously functioning thyroid nodule (AFTN) cases and 1725 non-AFTN cases. The total costs of the TSH strategy and non-TSH strategies were compared. The ratio of single-use costs of FNA to TS (CFNA/TS ) was used as the main outcome measure. RESULTS: Only when 6·03 ≤ CFNA/TS ≤ 27·17, the lowest total costs were associated with using the conventional TSH strategy. When CFNA/TS <6·03 or CFNA/TS >27·17, the lowest costs were found with FNA and TS, respectively. CONCLUSION: From the perspective of cost economics, in iodine-sufficient areas, we recommend that the decision on the use of TSH for the initial assessment of thyroid nodules should be based on the testing costs of FNA and TS in that medical unit.

Economic impact of and satisfaction with a high resolution thyroid nodule clinic at the endocrinology department. / Impacto económico y satisfacción de la implantación de una consulta de alta resolución de patología nodular tiroidea en Endocrinología.

BACKGROUND AND OBJECTIVE: No conclusive data exist on the value of a high resolution thyroid nodule clinic for management of nodular thyroid disease. The aim of this study was to evaluate the economic impact of and user satisfaction with a high resolution thyroid nodule clinic (HRTNC) in coordination with primary care. PATIENTS AND METHOD: A prospective, observational, descriptive study was conducted to analyze data from 3,726 patients (mean age 61±12 years; 85% women) evaluated at an HRTNC during 2014 and 2015. Demographic data (sex and age), number of ultrasound examinations and fine needle aspiration cytologies (FNAC), referral center and consultation type were assessed. RESULTS: In 2014 and 2015, 3,726 neck ultrasound examinations and 926 FNACs (3.8% rated as non-diagnostic) were performed. Among the 1,227 patients evaluated for the first time, 21.5% did not require a second endocrine appointment, which resulted in mean estimated savings of 14,354.55 euros. Of all patients, 41.1% were referred from primary care, 33.4% from endocrinology, and 26.5% from other specialties. As compared to 2013, the number of thyroid ultrasound examinations requested decreased by 65.3% and 59.7% in 2014 and 2015 respectively, with mean estimated savings of 137,563.92 euros. Mean user satisfaction assessed was 4.0 points (95% confidence interval, 3.7-4.3) on a 5-point scale. CONCLUSIONS: HRTNCs at endocrinology departments, coordinated with primary care, are a viable, cost-effective alternative with a positive user perception.

Utility and cost-effectiveness of molecular testing in thyroid nodules with indeterminate cytology.

CONTEXT: Molecular testing on biopsies from thyroid nodules with indeterminate cytology can improve patient management by preventing unnecessary surgeries on benign nodules. OBJECTIVE: The aim of the study was to determine the health outcome benefits and cost-effectiveness of molecular testing in nodules with AUS/FLUS or FN/SFN cytology. DESIGN: The initial diagnosis and treatment of a hypothetical cohort of adult U.S. patients with solitary thyroid nodules ≥1 cm was simulated by decision analytic modelling using Medicare cost estimates for three management strategies, standard of care without molecular testing (StC), gene expression classifier (GEC) and mutation and miRNA testing (MMT). RESULTS: Gene expression classifier decreased the rate of unnecessary surgeries by 32% relative to StC, yielding incremental costs of $1008 per patient or $5070 per unnecessary surgery avoided. MMT decreased the surgery rate by 67%, yielding incremental savings of -$1384 per patient or -$3170 per unnecessary surgery avoided. Results remained robust in deterministic sensitivity analyses; MMT was dominant for every variable tested. Independent of cancer prevalence, MMT yielded 52% fewer unnecessary surgeries relative to GEC #bib70% fewer two-stage thyroidectomies and correctly identified 70% more benign nodules. Test specificity had to be >68% for molecular testing to be cost-effective and decrease by >50% the rate of unnecessary surgeries performed on benign nodules. CONCLUSIONS: Molecular testing with high benign diagnostic yield can generate both positive health outcomes (less surgeries) and positive economic outputs (cost savings). These results are consistent with previously reported cost-utility data and provide valuable insights for informed decision-making by patients, physicians and payers.

American Thyroid Association Statement on Remote-Access Thyroid Surgery.

BACKGROUND: Remote-access techniques have been described over the recent years as a method of removing the thyroid gland without an incision in the neck. However, there is confusion related to the number of techniques available and the ideal patient selection criteria for a given technique. The aims of this review were to develop a simple classification of these approaches, describe the optimal patient selection criteria, evaluate the outcomes objectively, and define the barriers to adoption. METHODS: A review of the literature was performed to identify the described techniques. A simple classification was developed. Technical details, outcomes, and the learning curve were described. Expert opinion consensus was formulated regarding recommendations for patient selection and performance of remote-access thyroid surgery. RESULTS: Remote-access thyroid procedures can be categorized into endoscopic or robotic breast, bilateral axillo-breast, axillary, and facelift approaches. The experience in the United States involves the latter two techniques. The limited data in the literature suggest long operative times, a steep learning curve, and higher costs with remote-access thyroid surgery compared with conventional thyroidectomy. Nevertheless, a consensus was reached that, in appropriate hands, it can be a viable option for patients with unilateral small nodules who wish to avoid a neck incision. CONCLUSIONS: Remote-access thyroidectomy has a role in a small group of patients who fit strict selection criteria. These approaches require an additional level of expertise, and therefore should be done by surgeons performing a high volume of thyroid and robotic surgery.

Cost-Effectiveness of Diagnostic Lobectomy Versus Observation for Thyroid Nodules >4 cm.

BACKGROUND: The management of thyroid nodules >4 cm with benign cytology after fine-needle aspiration biopsy (FNAB) is controversial. FNAB is associated with a high false-negative rate in this setting, and may result in a delayed diagnosis and management of thyroid cancer. However, the majority of these nodules are benign. Therefore, the objective of this study was to determine the cost-utility of observation versus surgical management for thyroid nodules >4 cm with benign cytology after FNAB. METHODS: A microsimulation model comparing routine thyroid lobectomy with observation for low-risk patients with >4 cm thyroid nodules with benign FNAB cytology was constructed. Costs, quality-adjusted life-years (QALYs), and life-years gained were calculated over a lifetime time horizon from a U.S. Medicare perspective. RESULTS: The proportion of patients undergoing thyroid lobectomy for benign final pathology was 40% in the observation strategy versus 66% in the surgical strategy (p < 0.001). Overall, the surgical strategy was associated with higher lifetime costs compared with the observation strategy (incremental difference: + US$12,992 [confidence interval (CI) 13,042-13,524]), but also more QALYs (+0.12 QALYs [CI 0.02-0.24]) and longer life expectancy (+1.67 years [CI 1.00-2.41]). Incremental lifetime costs were lower for patients <55 years compared with those ≥55 years (+11,181 vs. +14,811, p < 0.001). The probability of cost-effectiveness of the surgical strategy was 49% at a $100k/QALY threshold or 65% at a $100k/life-year gained threshold. CONCLUSIONS: Routine thyroid lobectomy is associated with improved outcomes at an acceptable cost compared with observation for thyroid nodules >4 cm with benign cytology after FNAB. Surgical resection may be a cost-effective strategy to rule out malignancy in these nodules.

Analysis of an institutional protocol for thyroid lobectomy: Utility of routine intraoperative frozen section and expedited (overnight) pathology.

BACKGROUND: Intraoperative frozen section (FS) often is performed in patients who undergo thyroid lobectomy to determine the need for completion thyroidectomy. At our institution, if FS pathology is benign, final pathology is expedited overnight. The aim of this study was to determine the utility of FS and to identify a cost-effective management algorithm for thyroid lobectomy. METHODS: A retrospective review was performed of patients who underwent thyroid lobectomy between January 2009 and May 2013. Preoperative cytology ranged from "benign" to "suspicious for malignancy." Clinically significant cancers were defined as >1 cm in size, or multifocal microcarcinomas. RESULTS: Of the 192 patients who underwent thyroid lobectomy with FS, FS was suspicious for malignancy in 5 (3%) patients; 1 (0.5%) underwent immediate completion thyroidectomy. On final pathology, 9 (5%) patients had clinically significant cancers and underwent completion thyroidectomy. FS had a sensitivity and positive predictive value of 22% and 40%, respectively, in identifying clinically significant thyroid cancer. Cost of thyroid lobectomy at varying rates of same-day discharge favored thyroid lobectomy without FS but with expedited pathology for all scenarios. CONCLUSION: At our institution, there appears to be limited utility of FS at the time of thyroid lobectomy given the low predictive value for diagnosing a clinically significant thyroid cancer. In patients who are admitted overnight, expedited pathology is slightly less costly and may improve patient quality-of-life and decrease costs by avoiding delayed completion thyroidectomy. Overnight pathology for patients who undergo thyroid lobectomy may achieve modest cost-savings depending on institutional FS results and rates of malignancy.

Effect of malignancy rates on cost-effectiveness of routine gene expression classifier testing for indeterminate thyroid nodules.

BACKGROUND: The value of gene expression classifier (GEC) testing for cytologically indeterminate thyroid nodules lies in its negative predictive value, which is influenced by the prevalence of malignancy. We incorporated actual GEC test performance data from a tertiary referral center into a cost-effectiveness analysis of GEC testing. METHODS: We evaluated consecutive patients who underwent GEC testing for Bethesda category III and IV nodules from 2012 to 2014. Routine GEC testing was compared with conventional management by the use of a decision tree model. Additional model variables were determined via literature review. A cost-effectiveness threshold of $100,000 per quality-adjusted life-year (QALY) was used. RESULTS: The prevalence of malignancy was 24.3% (52/214). Sensitivity and specificity of GEC testing were 96% and 60%. Conventional management cost $11,119 and yielded 22.15 QALYs. Routine GEC testing was more effective and more costly, with an incremental cost-effectiveness ratio of $119,700/QALY, making it not cost-effective. At malignancy rates of 15, 25, or 35%, routine GEC testing became cost-effective when the cost of GEC testing fell below $3,167, $2,595, or $2,023. CONCLUSION: The cost-effectiveness of routine GEC testing varies inversely with the underlying prevalence of malignancy in the tested population. The value of routine GEC testing should be assessed within the context of institution-specific malignancy rates.

Utility of BRAF mutation detection in fine-needle aspiration biopsy samples read as "suspicious for papillary thyroid carcinoma".

BACKGROUND: The purpose of this study was to evaluate the diagnostic utility of BRAF mutation testing on thyroid nodules "suspicious for papillary thyroid carcinoma" (PTC) cytology. METHODS: A chart review of patients with fine-needle aspiration (FNA) results "suspicious for PTC" with subsequent thyroidectomy was performed. Corresponding archived FNA slides underwent BRAF mutation testing. RESULTS: Sixty-six patients with FNA "suspicious for PTC" underwent thyroidectomy. Forty-two (63.6%) had PTC diagnosed on final histopathology, whereas 21 (31.8%) had benign findings. Thirty-five patients (83%) with histologically proven PTC underwent total thyroidectomy, whereas 7 (17%) underwent hemithyroidectomy. BRAF mutation was detected in 17 of 49 samples (34.6%) available for testing and had 45.5% sensitivity, 87.5% specificity, 88.2% positive predictive value (PPV), and 43.8% negative predictive value (NPV) for diagnosing PTC. Two of 4 patients (50%) who underwent hemithyroidectomy with subsequent completion thyroidectomy had mutated BRAF detected. CONCLUSION: BRAF testing is a useful adjunct to improve PPV for patients with "suspicious for PTC" cytology.

Cost-effectiveness of FDG-PET/CT for cytologically indeterminate thyroid nodules: a decision analytic approach.

CONTEXT: Patients with thyroid nodules of indeterminate cytology undergo diagnostic surgery according to current guidelines. In 75% of patients, the nodule is benign. In these patients, surgery was unnecessary and unbeneficial because complications may occur. Preoperative fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) was found to have a very high negative predictive value (96%) and might therefore avoid futile surgery, complications, and costs. In the United States, two molecular tests of cytology material are routinely used for this purpose. OBJECTIVE: Five-year cost-effectiveness for routine implementation of FDG-PET/CT was evaluated in adult patients with indeterminate fine-needle aspiration cytology and compared with surgery in all patients and both molecular tests. DESIGN: A Markov decision model was developed to synthesize the evidence on cost-effectiveness about the four alternative strategies. The model was probabilistically analyzed. One-way sensitivity analyses of deterministic input variables likely to influence outcome were performed. SETTING AND SUBJECTS: The model was representative for adult patients with cytologically indeterminate thyroid nodules. MAIN OUTCOME MEASURES: The discounted incremental net monetary benefit (iNMB), the efficiency decision rule containing outcomes as quality-adjusted life-years and (direct) medical cost, of implementation of FDG-PET/CT is displayed. RESULTS: Full implementation of FDG-PET/CT resulted in 40% surgery for benign nodules, compared with 75% in the conventional approach, without a difference in recurrence free and overall survival. The FDG-PET/CT modality is the more efficient technology, with a mean iNMB of €3684 compared with surgery in all. Also, compared with a gene expression classifier test and a molecular marker panel, the mean iNMB of FDG-PET/CT was €1030 and €3851, respectively, and consequently the more efficient alternative. CONCLUSION: Full implementation of preoperative FDG-PET/CT in patients with indeterminate thyroid nodules could prevent up to 47% of current unnecessary surgery leading to lower costs and a modest increase of health-related quality of life. Compared with an approach with diagnostic surgery in all patients and both molecular tests, it is the least expensive alternative with similar effectiveness as the gene-expression classifier.

Cost-effectiveness of molecular testing for thyroid nodules with atypia of undetermined significance cytology.

CONTEXT: Novel molecular diagnostics, such as the gene expression classifier (GEC) and gene mutation panel (GMP) testing, may improve the management for thyroid nodules with atypia of undetermined significance (AUS) cytology. The cost-effectiveness of an approach combining both tests in different practice settings in North America is unknown. OBJECTIVE: The aim of the study was to determine the cost-effectiveness of two diagnostic molecular tests, singly or in combination, for AUS thyroid nodules. DESIGN AND SETTING: We constructed a microsimulation model to investigate cost-effectiveness from US (Medicare) and Canadian healthcare system perspectives. PATIENTS: Low-risk patients with AUS thyroid nodules were simulated. INTERVENTIONS: We examined five management strategies: 1) routine GEC; 2) routine GEC + selective GMP; 3) routine GMP; 4) routine GMP + selective GEC; and 5) standard management. MAIN OUTCOME MEASURES: Lifetime costs and quality-adjusted life-years were measured. RESULTS: From the US perspective, the routine GEC + selective GMP strategy was the dominant strategy. From the Canadian perspective, routine GEC + selective GMP cost and additional CAN$24 030 per quality-adjusted life-year gained over standard management, and was dominant over the other strategies. Sensitivity analyses reported that the decisions from both perspectives were sensitive to variations in the probability of malignancy in the nodule and the costs of the GEC and GMP. The probability of cost-effectiveness for routine GEC + selective GMP was low. CONCLUSIONS: In the US setting, the most cost-effective strategy was routine GEC + selective GMP. In the Canadian setting, standard management was most likely to be cost effective. The cost of these molecular diagnostics will need to be reduced to increase their cost-effectiveness for practice settings outside the United States.

Sentinel node biopsy in papillary thyroid cancer--what is the potential?

PURPOSE: Sentinel node biopsy (SNB) may identify lymph node metastases in patients with papillary thyroid cancer (PTC), enabling selective application of central node dissection (CND). The aim of this study was to assess the feasibility of implementing SNB in patients undergoing thyroidectomy for a cytologically indeterminate/suspicious/malignant thyroid nodule and to determine the potential improvement in clinical outcomes and the costs associated with the SNB technique. METHODS: The treatment strategies and clinical and pathological outcomes of two retrospective cohorts of patients who underwent preoperative thyroid FNA over a 5-year period in two different centres were studied. The potential for implementing the SNB technique and the benefits and costs associated with implementation were estimated. RESULTS: In centre 1, in 819 adult patients who had thyroid fine-needle aspiration cytology, the final cytology was indeterminate, suspicious and diagnostic of malignancy in 113, 29 and 28 patients, respectively. One hundred eight patients were 'suitable' for SNB. Twenty-three of these patients had PTC, six of whom underwent CND. Of these six patients, node metastasis was absent in five--the cohort in whom prophylactic CND may have been avoided consequent to a negative 'sentinel node' biopsy. Morbidity attributable to CND may have been avoided in up to four patients over a 5-year period. Costs associated with implementation of SNB outweighed any potential savings. Analysis of 491 patients in centre 2 confirmed that the benefit of SNB in PTC was similarly limited; morbidity attributable to CND may have been avoided in up to seven patients over a 5-year period. CONCLUSIONS: Even under ideal conditions (assuming 100 % node identification rate and 0 % false negative rate), the potential short- to medium-term benefit of sentinel node biopsy in patients with thyroid cancer in centres implementing a policy of selective or routine prophylactic CND is low.

Cost impact of molecular testing for indeterminate thyroid nodule fine-needle aspiration biopsies.

INTRODUCTION: Molecular testing of fine-needle aspiration (FNA) results helps diagnose thyroid cancer, although the additional cost of this adjunct has not been studied. We hypothesized that FNA molecular testing of two indeterminate categories (follicular lesion of undetermined significance and follicular/Hürthle cell neoplasm) can be cost saving. METHODS: For a hypothetical group of euthyroid patients with a 1-cm or larger solitary thyroid nodule, a decision-tree model was constructed to compare the estimated costs of initial evaluation according to the current American Thyroid Association guidelines, either with molecular testing (MT) or without [standard of care (StC)]. Model endpoints were either benign FNA results or definitive histological diagnosis. RESULTS: Molecular testing added $104 per patient to the overall cost of nodule evaluation (StC $578 vs. MT $682). In this distributed cost model, MT was associated with a decrease in the number of diagnostic lobectomies (9.7% vs. StC 11.6%), whereas initial total thyroidectomy was more frequent (18.2% vs. StC 16.1%). Although MT use added a diagnostic cost of $5031 to each additional indicated total thyroidectomy ($11,383), the cumulative cost was still less than the comparable cost of performing lobectomy ($7684) followed by completion thyroidectomy ($11,954) in the StC pathway, when indicated by histological results. In sensitivity analysis, savings were demonstrated if molecular testing cost was less than $870. CONCLUSIONS: Molecular testing of cytologically indeterminate FNA results is cost saving predominantly because of reduction in two-stage thyroidectomy. Appropriate use of emerging molecular testing techniques may thus help optimize patient care, improve resource use, and avoid unnecessary operation.