Molecular testing for cytologically suspicious and malignant (Bethesda V and VI) thyroid nodules to optimize the extent of surgical intervention: a retrospective chart review

Abstract

Background Molecular testing has been used for cytologically indeterminate thyroid nodules (Bethesda III and IV), where the risk of malignancy is 10–40%. However, to date, the role of molecular testing in cytologically suspicious or positive for malignancy (Bethesda V and VI) thyroid nodules has been controversial. The aim of this study was to determine whether patients who had molecular testing in Bethesda V and VI thyroid nodules had the optimal extent of surgery performed more often than patients who did not have molecular testing performed. Methods A retrospective chart review of 122 cases was performed: 101 patients from the McGill University teaching hospitals and 21 patients from the Hillel Yaffe Medical center, Technion University. Patients included in the study were those with Bethesda V or VI thyroid nodules who underwent molecular testing (ThyGenext® or ThyroseqV3®) (McGill n = 72, Hillel Yaffe n = 14). Patients with Bethesda V or VI thyroid nodules who did not undergo molecular testing were used as controls (McGill n = 29, Hillel Yaffe n = 7). Each case was reviewed in order to determine whether the patient had optimal surgery. This was defined as total thyroidectomy in the presence of either a positive lymph node, extrathyroidal extension, or an aggressive pathological variant of papillary thyroid carcinoma (tall cell, hobnail, columnar cell, diffuse sclerosing, and solid/trabecular) documented on the final pathology report. In all other cases, a lobectomy/hemi/subtotal thyroidectomy was considered as optimal surgery. Chi-squared testing was performed to compare groups. Results When molecular testing was done, 91.86% (79/86) of surgeries in the molecular testing group were optimal, compared to 61.11% (22/36) in the control group. At McGill University teaching hospitals and at Hillel Yaffe, 91.67% (66/72) and 92.86% (13/14) of surgeries in the intervention group were considered as optimal, respectively. This compares to 58.62% (17/29) at McGill and 71.43% (5/7) at Hillel Yaffe when molecular testing was not performed (p = .001, p = .186). Conclusions In this study, molecular testing in Bethesda V and VI thyroid tumors significantly improved the likelihood of optimal surgery. Therefore, molecular testing may have an important role in optimizing surgical procedures performed in the setting of Bethesda V and VI thyroid nodules. Prospective studies with larger sample sizes are required to further investigate this finding. Graphical abstract

Molecular Testing for Thyroid Nodules: The Experience at McGill University Teaching Hospitals in Canada

“…Subsequently, another study was done to investigate if using the molecular testing preoperatively in the patients with Bethesda V and Bethesda VI thyroid nodules with no evidence of high-risk disease can optimize the extent of surgery. The study showed that 91.86% of the surgeries in the molecular group was optimal while it was only 61.11% in the group without the preoperative molecular testing [ 58 ]. This finding shows that using molecular testing in these patients decreases the chances of under or overtreatment from 38.89% to 8.14%.…”

“…The main outcome was to identify how many patients had the optimal surgery done when using molecular testing compared to patients without molecular testing (for example: if a lobectomy was the surgery planned and performed, no completion was necessary following final histopathological analysis). It was found that 91.86% of the patients in the molecular group had an optimal surgery while it was only 61.11% in the group without molecular testing [ 58 ]…”

Molecular testing in fine‐needle aspiration of thyroid nodules

“…[7][8][9][10] Bethesda category V and VI nodules should continue to surgery; however, molecular testing of Bethesda category V and VI may lead to optimal primary surgery. 4,11 In summary, thyroid nodules >1.0 cm and reported as Bethesda category III and IV are recommended to undergo molecular testing, while molecular testing may be beneficial in Bethesda category V and VI in certain nodules. A flowchart summarizing the recommended clinical management of thyroid nodules via the Bethesda classification is included (Figure 1).…”

“…180 The goal of molecular testing is to optimize patient management, by reducing unnecessary surgery on benign thyroid nodules and by resolving thyroid cytology diagnostic dilemmas; however, the field has evolved to include prognostic implications and clinical management of malignant nodules. 11,181 Hier et al found that patients with Bethesda V and VI nodules with molecular testing more often had optimal surgery defined as a total thyroidectomy in the presence of positive lymph node, extrathyroidal extension, or an aggressive pathological variant of PTC such as tall cell, hobnail, columnar cell, diffuse sclerosing, and solid/trabecular or a version of a subtotal thyroidectomy in all other cases as compared to Bethesda V and VI without molecular testing. 11 The National Comprehensive Cancer Network guidance recommends testing for select mutations in advanced thyroid cancer due to new treatments available to increase iodine sensitivity or other targeted therapy.…”

“…11,181 Hier et al found that patients with Bethesda V and VI nodules with molecular testing more often had optimal surgery defined as a total thyroidectomy in the presence of positive lymph node, extrathyroidal extension, or an aggressive pathological variant of PTC such as tall cell, hobnail, columnar cell, diffuse sclerosing, and solid/trabecular or a version of a subtotal thyroidectomy in all other cases as compared to Bethesda V and VI without molecular testing. 11 The National Comprehensive Cancer Network guidance recommends testing for select mutations in advanced thyroid cancer due to new treatments available to increase iodine sensitivity or other targeted therapy. 182 Overall, the role of genetic alterations of thyroid carcinoma in clinical management is hopeful but should be determined by clinical trials.…”