Background
The 2015 American Thyroid Association (ATA) risk stratification system for differentiated thyroid cancer (DTC) is designed to predict recurring/persisting disease but not survival. Previous studies evaluating this system comprised relatively few patients with High Risk and/or follicular thyroid carcinoma (FTC). Therefore, we evaluated response to therapy, risk of recurrence as well as survival in a large population of High Risk DTC patients with a substantial proportion of FTC patients.

Methods
Adult patients, who fulfilled the 2015 ATA High Risk criteria and were diagnosed and/or treated for DTC at the Erasmus MC between January 2002 and December 2015, were retrospectively included. Response to therapy, recurrence, and mortality characteristics were obtained from patient records. Logistic regression and cox proportional hazards models were used to estimate the effects of ATA High Risk factors on response to therapy, recurrence and survival. Further, disease specific survival (DSS) was analyzed using the Kaplan-Meier method.

Results
We included 236 patients (63% women; 32% FTC). During follow-up, 49 patients (21%) died due to thyroid cancer. After initial therapy, 38 patients (16%) had excellent response, while 117 (50%) had structural disease. At final follow-up (median 72 months), 69 patients (29%) had excellent response, while 120 (51%) had structural disease. All risk factors, except large pathologic lymph nodes, were inversely related to excellent response at final follow-up. Recurrence occurred in 14% of the patients, and gross extra thyroidal extension at diagnosis increased the chance of recurrence significantly. Ten-year DSS was higher in the initial excellent response than in the structural disease group (100% vs. 61%).

Conclusion
In patients with High Risk DTC, the ATA risk stratification system is not only an excellent predictor of recurring/persisting disease, but also of survival. At final follow-up, half of the patients had persistent disease while one-third showed excellent response. Recurrence rates were higher than expected.