The 2015 American Thyroid Association (ATA) risk stratification system for differentiated thyroid cancer (DTC) is designed to predict recurring/persistent disease. Studies evaluating this system comprised relatively few patients with ATA High-Risk and/or follicular thyroid carcinoma.

Therefore, we aimed to evaluate response to therapy and risk of recurrence in a large population of High-Risk patients.

Adult patients diagnosed and/or treated for DTC at the Erasmus MC between January 2002 and December 2015, and fulfilling the 2015 ATA High-Risk criteria, were included. Demographical, disease, treatment, ATA response to therapy, recurrence, and mortality characteristics were retrospectively obtained from patient records. Response to therapy after first treatment, recurrence, mortality and radioactive iodine (RAI) refractory percentages were determined. Further, disease specific survival (DSS) was analyzed using the Kaplan-Meier (KM) method.

We included 235 patients (62% women) with ATA High-Risk; 156 patients (66%) had PTC, the others FTC. Mean age was 57 years and median follow-up 71 months. During follow-up, 49 patients (21%) died due to thyroid cancer. After initial therapy, 40 patients (17%) had excellent response,while 121 (52%) had structural disease. And at final follow-up, 72 patients (31%) had excellent response,while 117 (50%) had persistent structural disease. Survival was higher in the initial excellent response than in the initial structural disease group (10-year DSS 100% vs. 58% respectively). Further, 89 patients (38%) developed RAI refractory disease during follow-up,of which 64 (72%) were from the initial structural disease group.

In a population of ATA High-Risk patients, the ATA risk stratification system is an excellent initial predictor for both recurring/persistent disease and mortality. At final follow-up, 50% of the patients had persistent structural disease, while 30% showed excellent response. Furthermore, over 35% of the ATA High-Risk patients developed RAI refractory disease of which the majority had structural disease after initial therapy.