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Which Ultrasound Classification System is Best at Reducing Unnecessary Thyroid Nodule Biopsies?

BACKGROUND Thyroid nodules have a prevalence of 19% to 68% in the general population, with only 7% to 15% harboring thyroid cancer. Ultrasound (US) is now the primary radiologic tool for evaluating thyroid nodules, with several US features being predictive of malignancy-risk and, therefore, able to guide when a fine needle aspiration (FNA) biopsy may be advisable. Multiple medical specialty societies across the world have developed US-based risk stratification guidelines for thyroid nodules, in part to curb the significant testing and possible overtreatment of millions of benign thyroid nodules. A key design feature of the guidelines is to identify nodules with low risk of malignancy whose cytologic assessment with FNA can be safely deferred. Differences among the guidelines include the US lexicon, risk stratification category, quantitative versus qualitative grouping, and nodule size thresholds for FNA. Few studies, however, have compared the different guidelines to determine, which is best at identifying high-risk nodules or thyroid cancers while minimizing the number of “unnecessary” thyroid biopsies. We chose to compare studies that assessed large cohorts of thyroid nodules with known outcomes, had a blinded review of the US, and then applied various classification systems to see which performed best. Within these investigations, “unnecessary” thyroid biopsies are defined as biopsies, which would have been indicated by the particular classification system and ultimately turned out to be benign, either by cytology or histology. In this review, we focused on the negative predictive value (NPV) of the guidelines, representing the probability that a nodule is benign. We also looked at the rate of unnecessary FNAs and the probability that a nodule not selected for FNA was malignant, the false negative rate (FNR). We sought to clarify, which classification performed best with respect to the NPV, unnecessary biopsy rate, and FNR. This would indicate that the system was superior at identifying those nodules that did not require biopsy while simultaneously avoiding misclassifying malignancies as benign. Since most guidelines have a size threshold of 1 cm for FNA, this review only applied to thyroid nodules ≥1 cm.