Real-World Data Confirm 2015 ATA Risk Stratification System Predicts Response in DTC

The 2015 American Thyroid Association (ATA) Risk Stratification System is an excellent predictor of both persistent disease as well as survival in patients with high-risk differentiated thyroid cancer (DTC), including a subset of patients with follicular thyroid cancer (FTC) and papillary thyroid cancer (PTC), according to the findings from a real-world cohort of patients.

In this retrospective analysis, 236 adult patients diagnosed with DTC treated at the Erasmus Medical Center over a 13-year period were analyzed. This included 160 patients with PTC and 76 patients with FTC. The mean age was 56 years old, and the median follow-up was 6 years. All patients met high-risk criteria, as per the 2015 ATA Risk Stratification System.

Fifty-eight percent of patients had persistent disease after initial therapy. Of these patients, 51% had structural incomplete response and 7% has biochemical incomplete response. About a quarter of patients had intermediate response, while 17% had an excellent initial response.

During follow-up, 14% of 79 patients that achieved an excellent response developed a recurrence. At final follow-up, 55% of patients had persistent disease. Patients with FTC were more likely to have persistent disease than those with PTC, according to Evert F.S. van Velsen, MD, MSc, a doctoral student and internist in training at the Academic Center for Thyroid Diseases in the Department of Internal Medicine at Erasmus Medical Center in Rotterdam.

Overall, 69 patients (29%) had excellent response, and 120 patients (51%) has structural disease. Ten-year DSS was higher in patients with an initial excellent response (100%) compared to those who achieved initial structural disease (61%).

With the exception of large pathologic lymph nodes, all high-risk criteria in the 2015 ATA Risk Stratification System were inversely related to excellent response; this was also positively related to structural disease.

Of the 76 patients with FTC enrolled, 31 (41%) died compared to 39 (24%) of patients with PTC. However, this difference did not reach statistical significance.

In an interview withTargeted Oncology, van Velsen discussed the evaluation of the 2015 ATA Risk Stratification in patients with DTC, including patients with PTC and FTC. He also highlighted challenges in treating patients that have been defined as high-risk for recurrence.

TARGETED ONCOLOGY: What was the rationale for evaluating the 2015 ATA Risk Stratification System?

van Velsen:The ATA Risk Stratification System is designed to estimate the risk of disease recurrence. Nowadays it is widely used, and the key is the assessment of the response to therapy, [such as] dynamic risk stratification, which is performed for the first time 6 to 18 months after initial therapy, and thereafter continuously. If a patient achieves an excellent response, the risk of recurrence is typically low, around 1% - 4%. However, studies showing this were comprised of relatively few patients with ATA high-risk [patients]. Therefore, we evaluated the 2015 ATA Risk Stratification System in high-risk patients.

TARGETED ONCOLOGY: What is the frequency of recurrence in patients with PTC versus FTC?

van Velsen:We found a recurrence rate after an excellent response of 14% for the whole population. This was 17% for PTC and 5% for FTC. However, these percentages were not significantly different from each other.

The treatment options from recurrent disease are dependent on the extent of the recurrence. In the case of biochemical disease or distant metastases, a physician might choose [to administer] radioiodine therapy. Meanwhile, in patients with recurrent disease in the neck region, surgery is usually the first option, which can be followed by radioiodine therapy.

TARGETED ONCOLOGY: What were the methods of design for this study?

van Velsen:We conducted a retrospective cohort study in which we included adult patients with either PTC or FTC. All included patients fulfilled the 2015 ATA High Risk criteria. The median follow-up was 72 months. We used statistical models to estimate the effects of DTC subtype and ATA high-risk criteria on response to therapy, recurrence, as well as overall survival and disease-specific survival.

TARGETED ONCOLOGY: What did you find in this analysis?

van Velsen:We found a recurrence rate after an excellent response of 14% for the whole population. At end of follow-up, 29% of the patients had no evidence of disease, while still, 55% had persistent disease, either biochemical or structural.  All ATA High Risk criteria, except large pathologic lymph nodes, were inversely related to excellent response and positively related to structural disease at final follow-up.

TARGETED ONCOLOGY: How did these results compare to that of previous studies that investigated the 2015 ATA Risk Stratification System?

van Velsen:The 2015 ATA Guidelines cite a recurrence rate of 1% - 4% in DTC patients with an excellent response. However, this is predominantly based on recurrence rates in ATA low- and intermediate-risk patients. Previous studies on high-risk patients showed, like [we found in our data], higher recurrence rates of 14% - 30% in this patient population.

TARGETED ONCOLOGY: How did responses vary in patients with FTC as opposed to PTC?

van Velsen:For the response after the first therapy, we did not find any differences between PTC and FTC. However, at final follow-up, patients with FTC  had significantly more often structural disease.

No statistical differences in recurrences rates were seen between FTC and PTC.

TARGETED ONCOLOGY: What is important for the community oncologist to take home from this research?

van Velsen:We feel that our findings contribute to the knowledge about the clinical value of the 2015 ATA Risk Stratification System, especially regarding risk of recurrence in high-risk patients. Thereby, [this study] provides a direction for use in daily clinical practice.

Clinicians should be aware of this substantially high risk of recurrence when treating and following up on high-risk patients [with thyroid cancer].

Reference:

van Velsen EFS, Stefenfa MT, van Kemenade FJ, et al. Evaluating the 2015 American Thyroid Association Risk Stratification System in High-Risk Papillary and Follicular Thyroid Cancer Patients.Thyroid.2019 29:8, 1073-1079. doi: 10.1089/thy.2019.0053