• Morris Luc G T LGT Head and Neck Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York..
• Head and Neck Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
• JAMA Otolaryngol Head Neck Surg. 2020 Sep 1; 146 (9): 845-850.

ImportanceAdvances in genomic technologies have facilitated the development of sophisticated molecular diagnostic tests for thyroid nodules, in the hopes of better risk stratifying nodules with indeterminate cytopathologic diagnosis. It is unclear whether the widespread, or reflexive, use of these tests will improve outcomes for patients with thyroid nodules.ObservationsThyroid nodules are a common and essentially normal finding. Even cytologically indeterminate thyroid nodules have a very low probability (approximately 1%) of representing clinically aggressive cancers and an even lower probability (approximately 0.1%) of representing lethal cancers. Therefore, most indeterminate thyroid nodules are low risk. Even if some will eventually require surgery, many can initially be kept under surveillance rather than requiring immediate surgery. Clinical and radiographic features can be helpful in risk stratifying these nodules. Molecular assays are marketed as tools to improve risk stratification for cytologically indeterminate thyroid nodules. However, the performance of these tests varies markedly across different practice settings, and the predictive value of these tests in real world practice may be lower than the numbers provided on laboratory reports. It is unclear whether these assays improve patient outcomes, such as survival or quality of life, or substantially reduce the number of thyroid surgeries performed.Conclusions And RelevanceBecause of variable performance, unclear benefit to patients, and questionable cost-effectiveness, clinical practice guidelines in the US and Europe currently do not recommend the universal, reflexive use of molecular assays for cytologically indeterminate thyroid nodules. These tests might offer value when used in selected scenarios, although this is not well understood. Future research should address whether the routine use of these molecular diagnostic tests leads to superior patient survival or quality-of-life outcomes compared with management based on clinical and radiographic criteria.

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