[(18)F]FDG-PET/CT to prevent futile surgery in indeterminate thyroid nodules: a blinded, randomised controlled multicentre trial

PURPOSE: To assess the impact of an [(18)F]FDG-PET/CT-driven diagnostic workup to rule out malignancy, avoid futile diagnostic surgeries, and improve patient outcomes in thyroid nodules with indeterminate cytology. METHODS: In this double-blinded, randomised controlled multicentre trial, 132 adult euthyroid patients with scheduled diagnostic surgery for a Bethesda III or IV thyroid nodule underwent [(18)F]FDG-PET/CT and were randomised to an [(18)F]FDG-PET/CT-driven or diagnostic surgery group. In the [(18)F]FDG-PET/CT-driven group, management was based on the [(18)F]FDG-PET/CT result: when the index nodule was visually [(18)F]FDG-positive, diagnostic surgery was advised; when [(18)F]FDG-negative, active surveillance was recommended. The nodule was presumed benign when it remained unchanged on ultrasound surveillance. In the diagnostic surgery group, all patients were advised to proceed to the scheduled surgery, according to current guidelines. The primary outcome was the fraction of unbeneficial patient management in one year, i.e., diagnostic surgery for benign nodules and active surveillance for malignant/borderline nodules. Intention-to-treat analysis was performed. Subgroup analyses were performed for non-Hürthle cell and Hürthle cell nodules. RESULTS: Patient management was unbeneficial in 42% (38/91 [95% confidence interval [CI], 32–53%]) of patients in the [(18)F]FDG-PET/CT-driven group, as compared to 83% (34/41 [95% CI, 68–93%]) in the diagnostic surgery group (p < 0.001). [(18)F]FDG-PET/CT-driven management avoided 40% (25/63 [95% CI, 28–53%]) diagnostic surgeries for benign nodules: 48% (23/48 [95% CI, 33–63%]) in non-Hürthle cell and 13% (2/15 [95% CI, 2–40%]) in Hürthle cell nodules (p = 0.02). No malignant or borderline tumours were observed in patients under surveillance. Sensitivity, specificity, negative and positive predictive value, and benign call rate (95% CI) of [(18)F]FDG-PET/CT were 94.1% (80.3–99.3%), 39.8% (30.0–50.2%), 95.1% (83.5–99.4%), 35.2% (25.4–45.9%), and 31.1% (23.3–39.7%), respectively. CONCLUSION: An [(18)F]FDG-PET/CT-driven diagnostic workup of indeterminate thyroid nodules leads to practice changing management, accurately and oncologically safely reducing futile surgeries by 40%. For optimal therapeutic yield, application should be limited to non-Hürthle cell nodules. TRIAL REGISTRATION NUMBER: This trial is registered with ClinicalTrials.gov: NCT02208544 (5 August 2014), https://clinicaltrials.gov/ct2/show/NCT02208544. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00259-021-05627-2.