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

Purpose: 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 cancer patients (DTC). While age at diagnosis has already been assessed in high-risk patients, it remains to be established in Low and Intermediate-Risk patients. 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 Intermediate-Risk group, patients ≥55 years had higher rate of structural disease (11.6% versus 8.9%), recurrent disease (4.1% versus 0.7%) and death (4.1% versus 1%) when compared with younger patients (<55years) (p=0.007). Multivariate analysis confirmed that older age at diagnosis (OR=3.9, 95%-CI: 1.9-8.6, p<0.001) 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<0.001), T (OR=32, 95%-CI: 1.4-7.1, p=0.005) and N category (OR=2.3, 95%-CI: 1.1-5.0, p=0.03). Nevertheless, a negative impact 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 patient with persistent structural disease after initial therapy (p<0.001) and to 80% in patients older than 55 years and persistent structural disease after initial therapy (p=0.02). Conclusions: Our results suggest that age at diagnosis further predict individual outcomes in Intermediate-Risk DTC allowing ongoing management to be tailored accordingly.