Endocrine Abstracts

Objectives: Molecular diagnostic tests for indeterminate thyroid nodules (ITNs) are marketed based on negative predictive value (NPV) and benign call rate. Arguments that unnecessary surgeries are avoided based on NPV/BCR incorrectly assume that all ITNs would undergo diagnostic surgery in the absence of molecular testing. In our practice with centralized triage and cytopathology the resection and malignancy rate, respectively, were 21% and 26% for AUS/FLUS and 56% and 43% for FN/SFN, prior to molecular testing implementation. If each positive molecular test result triggered surgery, implementation of molecular testing would substantially increase overtreatment. Therefore, following optimization of ultrasound malignancy risk assessment (Wu et al ETJ 2022) and evaluation of local malignancy rates (Ghaznavi et al Acta Cytologica 2022) in each Bethesda cytologic category for our diagnostic pathway, we locally developed and validated ThyroSPEC, a low-cost (C=650) molecular diagnostic test that detects 117 point mutations and 23 gene fusions in residual routine FNA material.

Methods: We followed 615 consecutive patients with ITN from July 2020 to July 2022 with reflex ThyroSPEC testing in the context of a centralized, optimized thyroid nodule diagnostic pathway to determine the strengths and gaps of this integrated diagnostic pathway.

Results: The resection rate for ITNs was 217/615 (35%) with molecular testing at a 59/143 (41%) prevalence of malignancy in AUS/FLUS and 21/41 (51%) prevalence of malignancy in FN/SFN, a relative increase of 13% (P = 0.0913) in the resection rate and 15% (P = 0.2438) in the malignancy rate since implementation of ThyroSPEC.

Conclusions: This ongoing study involved first optimizing the local ultrasound and cytology practices as major factors in decision-making, then implementing a custom molecular test into a low resection rate thyroid nodule diagnostic pathway. This resulted in improved decision-making and higher diagnostic yield particularly for diagnostically difficult ultrasound intermediate suspicion nodules.