Real-time ultrasound elastography in the diagnosis of newly identified thyroid nodules in adults: the ElaTION RCT.

Background: Strain and shear wave elastography which is commonly used with concurrent real-time imaging known as real-time ultrasound shear/strain wave elastography is a new diagnostic technique that has been reported to be useful in the diagnosis of nodules in several organs. There is conflicting evidence regarding its benefit over ultrasound-guided fine-needle aspiration cytology alone in thyroid nodules.

Objectives: To determine if ultrasound strain and shear wave elastography in conjunction with fine-needle aspiration cytology will reduce the number of patients who have a non-diagnostic first fine-needle aspiration cytology results as compared to conventional ultrasound-only guided fine-needle aspiration cytology.

Design: A pragmatic, unblinded, multicentre randomised controlled trial.

Setting: Eighteen centres with a radiology department across England.

Participants: Adults who had not undergone previous fine-needle aspiration cytology with single or multiple nodules undergoing investigation.

Interventions: Ultrasound shear/strain wave elastography-ultrasound guided fine-needle aspiration cytology (intervention arm) - strain or shear wave elastography-guided fine-needle aspiration cytology. Ultrasound-only guided fine-needle aspiration cytology (control arm) - routine ultrasound-only guided fine-needle aspiration cytology (the current standard recommended by the British Thyroid Association guidelines).

Main outcome measure: The proportion of patients who have a non-diagnostic cytology (Thy 1) result following the first fine-needle aspiration cytology.

Randomisation: Patients were randomised at a 1 : 1 ratio to the interventional or control arms.

Results: A total of 982 participants (80% female) were randomised: 493 were randomised to ultrasound shear/strain wave elastography-ultrasound guided fine-needle aspiration cytology and 489 were randomised to ultrasound-only guided fine-needle aspiration cytology. There was no evidence of a difference between ultrasound shear/strain wave elastography and ultrasound in non-diagnostic cytology (Thy 1) rate following the first fine-needle aspiration cytology (19% vs. 16% respectively; risk difference: 0.030; 95% confidence interval -0.007 to 0.066; p = 0.11), the number of fine-needle aspiration cytologies needed (odds ratio: 1.10; 95% confidence interval 0.82 to 1.49; p = 0.53) or in the time to reach a definitive diagnosis (hazard ratio: 0.94; 95% confidence interval 0.81 to 1.10; p = 0.45). There was a small, non-significant reduction in the number of thyroid operations undertaken when ultrasound shear/strain wave elastography was used (37% vs. 40% respectively; risk difference: -0.02; 95% confidence interval -0.06 to 0.009; p = 0.15), but no difference in the number of operations yielding benign histology - 23% versus 24% respectively, p = 0.70 (i.e. no increase in identification of malignant cases) - or in the number of serious adverse events (2% vs. 1%). There was no difference in anxiety and depression, pain or quality of life between the two arms.

Limitations: The study was not powered to detect differences in malignancy.

Conclusions: Ultrasound shear/strain wave elastography does not appear to have additional benefit over ultrasound-guided fine-needle aspiration cytology in the diagnosis of thyroid nodules.

Future work: The findings of the ElaTION trial suggest that further research into the use of shear wave elastography in the diagnostic setting of thyroid nodules is unlikely to be warranted unless there are improvements in the technology. The diagnostic difficulty in distinguishing between benign and malignant lesions still persists. Future studies might examine the role of genomic testing on fine-needle aspiration samples. There is growing use of targeted panels of molecular markers, particularly aimed at improving the diagnostic accuracy of indeterminate (i.e. Thy3) cytology results. The application of these tests is not uniform, and their cost effectiveness has not been assessed in large-scale trials.

Study registration: This study is registered as ISRCTN (ISRCTN18261857).

Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 12/19/04) and is published in full in Health Technology Assessment; Vol. 28, No. 46. See the NIHR Funding and Awards website for further award information.