Prognostic Factors Improving ATA Risk System and Dynamic Risk Stratification in Low- and Intermediate-Risk DTC Patients

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Abstract
Context: American Thyroid Association (ATA) guidelines do not consider age at diagnosis as a prognostic factor on the estimation of the risk of persistent/recurrent disease in differentiated thyroid carcinoma (DTC) patients. While age at diagnosis has already been assessed in high-risk patients, it remains to be established in low- and intermediate-risk patients. Objective: The aim of our study was to investigate the role of age as a prognostic factor in the short- and long-term outcome of DTC patients classified at low and intermediate risk according to the ATA stratification risk system. Methods: We retrospectively evaluated 863 DTC patients (mean follow-up: 10 ± 6.2 years) 52% classified as low (449/863) and 48% as intermediate risk (414/863). For each ATA-risk class patients were divided into subgroups based on age at diagnosis (<55 or ≥55 years). Results: In the intermediate-risk group, patients aged 55 years or older had a higher rate of structural disease (11.6% vs 8.9%), recurrent disease (4.1% vs 0.7%), and death (4.1% vs 1%) when compared with younger patients (<55 years) (P = .007). Multivariate analysis confirmed that older age at diagnosis (odds ratio [OR] = 3.9; 95% CI, 1.9-8.6; P < .001) was an independent risk factor for worse long-term outcome together with response to initial therapy (OR = 13.0; 95% CI, 6.3-27.9; P < .001), and T (OR = 32; 95% CI, 1.4-7.1; P = .005) and N category (OR = 2.3; 95% CI, 1.1-5.0; P = .03). Nevertheless, a negative effect of older age was documented only in the subgroup of intermediate DTC patients with persistent structural disease after initial therapy. Indeed, the rate of worse long-term outcome rose from 13.3% in the whole population of intermediate DTC patients to 47.8% in patients with persistent structural disease after initial therapy (P < .001) and to 80% in patients older than 55 years and persistent structural disease after initial therapy (P = .02). Conclusion: Our results suggest that age at diagnosis further predict individual outcomes in Intermediate-Risk DTC allowing ongoing management to be tailored accordingly.

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