A narrative review of molecular testing for indeterminate thyroid nodules: living with the results

Background and Objective: By age 50, the majority of Americans will have one or more thyroid nodules incidentally discovered. Thyroid nodules may be biopsied via fine-needle-aspiration (FNA), and nearly 100,000 nodules are graded cytologically indeterminate every year in the US, yielding a diagnostic dilemma. Molecular testing has emerged as a modality to aid in risk stratifying these indeterminate thyroid nodules to avoid unnecessary diagnostic surgery. To date, few studies have investigated quality of life (QOL) associated with molecular testing for indeterminate thyroid nodules. Our aim in this review is to discuss the findings, implications, and limitations of these studies. Methods: A literature review was performed using PubMed to search all original articles published in the English language over the last 30 years that assessed QOL in patients undergoing molecular testing for indeterminate thyroid nodules. Key Content and Findings: The two most relevant studies assessed QOL in patients with indeterminate cytology who underwent molecular testing followed by observation or surgery, both at an initial timepoint and then longitudinally. Patients with benign cytology and a benign molecular test result experienced similar QOL. Patients with malignant cytology had increased impairment of daily life but otherwise no other differences in QOL, compared to those with a suspicious molecular test. A suspicious molecular test was associated with worse initial QOL compared to a benign molecular test. Patients who underwent surgery for suspicious molecular test reported improved QOL after surgery compared to before. The small subset of patients opting for active surveillance after receiving a suspicious molecular test reported similar QOL as those with a benign molecular test. Conclusions: While there was some loss to follow up, these studies may provide reassurance that patients view a benign molecular test similarly to benign cytology. A suspicious molecular result may initially be associated with worse QOL compared to a benign molecular result, but QOL differences seem to disappear at early follow up, likely reflecting the large proportion of patients with suspicious molecular testing who undergo surgery and subsequently report improvement in nearly all QOL domains compared to their baseline.