The Clinical Utility of Molecular Testing in the Management of Thyroid Follicular Neoplasms (Bethesda IV Nodules)

Objective: FN present a management quandary as they are often benign but may also be aggressive TC. Consensus recommendations have historically advised thyroidectomy for definitive diagnosis. Although MT have robust benefit in hypothetical cost analyses, under current management guidelines a real-time study of their clinical utility in FN is awaited. We investigate if MT use for FN directs appropriate thyroidectomy for TC while triaging to surveillance nodules that are likely benign. Methods: Data were analyzed for 389 consecutive patients managed from 11/14 to 9/19 for 405 FN, excluding oncocytic neoplasms. TC was defined as same-nodule histologic malignancy. When obtained, MT was performed using ThyroSeq (TS) v2 or 3. Results: With a mean nodule size of 2.7 +/- 1.3 cm, MT was used in 89% and was positive in 39%. When MT was positive, thyroidectomy was more often utilized (91% v. MT-27%; P < 0.001) and more likely for histologic TC (70% vs 16%, P < 0.001). With preoperative MT, all American Thyroid Association intermediate, high-risk, and medullary TC were positive whereas all MT- malignancies were low-risk. With TSv3, ultrasound surveillance was more likely for MT-FN (90% vs TSv2 65%, P < 0.001), and occurred for a total of 174 MT-FN. With mean follow-up of 24.6 months, 82% remained stable in size. Conclusions: MTuse for FN increased the surgical yield of cancer by 4-fold, identified all potentially aggressive malignancies, and allowed apparently safe nonoperative surveillance for >80% of MT-negative patients. Thyroid nodule MT optimizes patient outcomes sufficiently to justify its incorporation into routine practice.