The prevalence of thyroid nodules in the general population is high, but only about 5% are malignant lesions. Cytology is usually appropriate to rule out malignancy in sonographically suspicious nodules, but in many cases reports are indeterminate. Molecular testing is a more recent approach to rule out malignancy and guide subsequent management.
We recently reported the development and analytical validation of a novel dual-component molecular assay as an ancillary method to improve clinical decision-making in patients with indeterminate thyroid nodule cytology. The assay involves next-generation sequencing (NGS) based detection of mutations in 23 thyroid cancer related genes and digital polymerase chain reaction (dPCR) evaluation of the expression levels of a microRNA strongly associated with thyroid cancer. The assay is planned as a ruling out test and preliminary results showed a negative predictive value comparable to a negative diagnostic cytology.
Aim of this proposal is to describe the performance of the novel dual molecular assay in a real-world cohort of cytologically indeterminate thyroid nodules and to evaluate whether the use of this test in real-world clinical routine can reduce the rates of surgeries for indeterminate thyroid nodules.
Thyroid nodules are being identified with increasing frequency in clinical practice, but very few of the lesions are actually malignant (7¿15% of cases). Fine-needle aspiration cytology is the most reliable method for identifying these lesions preoperatively, but up to 30% of thyroid FNA samples yield indeterminate results.
A high proportion of these patients are subjected to diagnostic surgery, but only a minority of resected indeterminate thyroid nodules are histologically diagnosed as malignant, ranging from 15.9% for Bethesda class III up to 26.1% for Bethesda class IV.
Assessment of molecular markers in FNA samples can add diagnostically valuable information to that provided by cytology, thereby improving preoperative risk stratification for indeterminate nodules. While molecular markers for thyroid nodule diagnosis evolve, the clinician still asks whether they can safely not recommend surgery to asymptomatic patients with indeterminate nodule and negative molecular test.
Real-world data like those proposed in this study are critical to making such decisions and sharing pragmatic experience using molecular tests for cytologically indeterminate (Bethesda III and IV) thyroid nodules.
Randomized controlled trials are the gold standard for evidence-based medicine, however they do not always reflect real-world patient populations, limiting their generalizability and external validity. Real-world evidence, generated during routine clinical practice, is increasingly important in determining effectiveness outside of the tightly controlled conditions of randomized controlled trials, and is now recognized by regulatory bodies as a valuable complement to randomized controlled trials. Consequently, it is increasingly important for physicians to understand how real-world evidence data can be used alongside clinical trial data.