Genetic testing for indeterminate thyroid cytology: review and meta-analysis

Abstract

Thyroid cancer is the most frequent endocrine malignancy, and its incidence is increasing. A current limitation of cytological evaluation of thyroid nodules is that 20–25% are reported as indeterminate. Therefore, an important challenge for clinicians is to determine whether an indeterminate nodule is malignant, and should undergo surgery, or benign, and should be recommended to follow-up. The emergence of precision medicine has offered a valuable solution for this problem, with four tests currently available for the molecular diagnosis of indeterminate cytologies. However, efforts to critically analyze the quality of the accumulated evidence are scarce. This systematic review and meta-analysis is aimed to contribute to a better knowledge about the four available molecular tests, their technical characteristics, clinical performance, and ultimately to help clinicians to make better decisions to provide the best care options possible. For this purpose, we address three critical topics: (i) the proper theoretical accuracy, considering the intended clinical use of the test (rule-in vs rule-out) and the impact on clinical decisions; (ii) the quality of the evidence reported for each test (iii) and how accurate and effective have the tests proved to be after their clinical use. Together with the upcoming evidence, this work provides significant and useful information for healthcare system decision-makers to consider the use of molecular testing as a public health need, avoiding unnecessary surgical risks and costs.

Ultrasound characteristics of thyroid nodules facilitate interpretation of the malignant risk of Bethesda system III/IV thyroid nodules and inform therapeutic schedule

“…Rossi Met et al attempted to better define the management of Bethesda system III/IV nodules by introducing cytological subcategories, concluding that surgery may be applied in part of Bethesda system III and all Bethesda system IV nodules and that repeated FNA and follow‐up may be useful in part of Bethesda system III nodules. Vargas‐Salas et al addressed three critical topics for clinicians to facilitate improved decisions for treating thyroid nodules. They think molecular testing should be considered a public health measure, avoiding unnecessary surgical risk and cost.…”

Molecular mutations as a possible factor for determining extent of thyroid surgery

“…Molecular testing is a diagnostic tool that is used to better understand the nature of thyroid nodules preoperatively. Much of the literature has focused on molecular testing's ability to determine whether a patient with an indeterminate thyroid nodule requires surgery [2,3,[20][21][22][23]. Our study's aim was to take the analysis one step further and to determine whether molecular testing can help with decisionmaking on the optimal surgical treatment, including the extent and timing of surgery for patients with a thyroid nodule that was suspicious or malignant on thyroid FNA.…”

Review of a single institution's fine needle aspiration results for thyroid nodules: Initial observations and lessons for the future

“…In other words, if the pre‐test probability, determined by the calculated Bethesda 4 category malignancy rate, is similar to or higher than the molecular testing's PPV then it does not change the clinical management. Other genetic tests that do not have a high NPV, and thus do not aim to rule‐out patients, might have a role in patients with an FNA result that encompasses a high malignancy rate . Nevertheless, molecular testing for the diagnosis of thyroid cancer may assist the clinician's decision on the appropriate management for the B3 indeterminate group as well as for FNA samples with insufficient quantity of cells for cytological interpretation …”