433 Letter: preoperative stratification by [18F]FDG-PET 9 negative were difficult to classify and required next generation sequencing to determine the nature of the nodule [661]. Mean one-year societal costs, adjusted for imbalance in malignancy rate in both study arms despite successful stratification, were almost €7,000 lower in the [18F]FDG-PET/ CT-driven approach. This included additional diagnostics and other costs due to incidental findings in the skull-base to aortic arch PET/CT-acquisition. Extending the one-year window to a life-long horizon confirmed that this imaging-driven approach is cost-effective both for direct and societal costs with almost €10,000 lifetime reduction in costs [663]. The reassurance of a negative [18F] FDG-PET/CT resulted in sustained health-related quality of life throughout the first year of active surveillance. Diagnostic surgery for a nodule with benign histopathology resulted in more cognitive impairment and physical problems including cosmetic complaints, but improved goitre symptoms and anxiety. Anxiety was also reduced in patients with malignant histopathology [664]. Quantitative analyses confirmed that an [18F]FDG-PET/CT-driven approach is specifically effective in non-Hürthle nodules, although it suggested that using a different cut-off of the Standardised Uptake Value in Hürthle nodules might improve the diagnostic value of [18F]FDG-PET/CT in this subcategory of patients [662]. We could not find image-based or immunohistochemical markers that explain the difference between true and false [18F]FDG-positive nodules [662, 665] and are currently preparing a manuscript on the comparative value of molecular imaging and molecular diagnostics in our cohort. Admittedly, initial follow-up was relatively short with a final evaluation after only one year, which was chosen due to rules set by the grant provider (Dutch Cancer Society). However, all patients remained in clinical follow-up up to 5 years, and to date no missed cancer diagnoses have been reported. Long-term analyses of our cohort are scheduled in 2025. Secondly, during the execution of the trial, TI-RADS stratification of thyroid nodules by ultrasound characteristics was not routinely performed in the Netherlands. As it is currently being incorporated in routine clinical care, it might influence the RoM of selected cytologically indeterminate thyroid nodules and thus benign call rate and NPV of [18F]FDG-PET/CT. In conclusion, we truly believe that that data from the Dutch EfFECTS trial confirm earlier publications by our group as well as others: the use of [18F]FDG-PET/CT in cytologically indeterminate thyroid nodules prevents unbeneficial diagnostic thyroid surgery, is oncologically safe, cost-effective and preserves quality of life. Its use is practice changing, should be offered to any patients scheduled for diagnostic surgery for indeterminate thyroid FNAC, and will be part of the updated Dutch national guideline (expected end of 2023). We call to push forward now and not to look back until the role of [18F]FDG-PET/CT in cytologically indeterminate thyroid nodules has embodied in the bright daylight of guidelines. Looking back too soon might send back Euridice to the underworld forever and even Orpheus was not able to undertake a return-trip to Hades a second time.
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