18F–FDG–PET/CT may reduce unnecessary thyroid surgery in cytologically indeterminate thyroid nodules

Despite the availability of thyroid fine-needle aspiration and cytology, precise presurgical diagnoses of follicular-patterned lesions has yet to be achieved. A cytologically indeterminate finding is probably the most common matter that clinicians and patients discuss during the evaluation of thyroid nodules and is a source of anxiety for both (1). The avoidance of unnecessary “diagnostic” surgeries is one of the main clinical goals for patients with indeterminate cytology (Bethesda classes III and IV). Potential solutions proposed in the past several years have included repeat biopsy, sonographic risk restratification, ancillary imaging techniques, and molecular testing—the latter has become quite popular in the United States but is not yet readily available in many other parts of the world. 18F-FDG–PET imaging is not routinely recommended for evaluating thyroid nodules with indeterminate cytology, according to American Thyroid Association guidelines (2), owing to the limited and moderate-quality evidence available at the time of their writing. This study (3) is the first randomized clinical trial to evaluate the impact of 18F-FDG–PET/CT on the outcomes of patients with indeterminate thyroid nodules, representing those who are already candidates for surgical resection according to local practices as assessed by a multidisciplinary team. The investigators demonstrated that 18F-FDG–PET/CT-driven management resulted in a 40% reduction of unnecessary surgeries during 1-year follow-up and societal savings of approximately €6,900 per patient. This is a great news for patients with indeterminate thyroid nodules, as it introduces another management option for this issue. However, as the authors themselves acknowledge, the negative predictive value may be slightly overestimated. The reference standard for the 18F-FDG–PET/CT cohort should be interpreted cautiously. Nodules that remained unchanged on the 1-year ultrasound after a negative 18F-FDG–PET/CT result were considered true negatives. Conversely, patients with 18F-FDG-positive nodules who refused surgery experienced no change during short-term follow-up (28–42 months) and were deemed benign (and thus, false positive). However, lack of growth in such a short time does not necessarily imply benignity (4), and follicular neoplasms usually do not display classic sonographic suspicious features (5). On the other hand, growth does not equal malignancy; the two nodules in the current study that grew and underwent surgery were confirmed as histologically benign. The drawbacks of an 18F-FDG–PET/CT-driven approach include the potential discovery of incidentalomas: the current series reported 21 18F-FDG-positive incidental thyroid nodules, from which 13 additional biopsies and 11 resections were performed. In 4 patients, the surgery was extended to total thyroidectomy; in all cases, these incidental lesions were benign at final histopathologic investigation. Overall, 18F-FDG–PET/CT represents an additional, promising option for clinicians confronted with cytologically indeterminate thyroid nodules. However, this approach does not apply to Hürthle-cell nodules, which are nearly all 18F-FDG-positive, irrespective of final histopathology. There are no unique solutions for these patients, who may benefit from a multifaceted approach to better estimate their malignancy risk.