Analysis of age and disease status as predictors of thyroid cancer-specific mortality using the Surveillance, Epidemiology, and End Results database

Abstract

Background: Age at diagnosis is incorporated into all relevant staging systems for differentiated thyroid carcinoma (DTC). There is growing evidence that a specific age cutoff may not be ideal for accurate risk stratification. We sought to evaluate the interplay between age and oncologic variables in patients with DTC using the largest cohort to date.

Methods: The Surveillance, Epidemiology, and End RESULTS (SEER) database was queried to identify patients with DTC as their only malignancy for the period 1973 to 2009. Multivariate analyses using a range of age cutoffs and age subgroupings were utilized in order to search for an optimal age that would provide the most significant risk stratification between young and old patients. The primary outcome was disease-specific survival (DSS) and covariates included: age, race, sex, tumor/nodal/metastasis (TNM) stage, decade of diagnosis, and radioactive iodine therapy.

Results: A total of 85,740 patients were identified. Seventy-six percent of patients were American Joint Committee on Cancer (AJCC) stage I, 8% were stage II, 7% were stage III, and 8% were stage IV. Age over 45 years (hazard ratio [HR] 19.2, p<0.001) and metastatic disease (HR 13.1, p<0.001) were the strongest predictors of DSS. Other factors that significantly predicted DSS included: not receiving radioactive iodine (RAI; HR 1.3, p=0.002), T3 (HR 2.6, p<0.001), and T4 disease (HR 3.3, p<0.001), and nodal spread (HR 2.6 to 3.3, p<0.001). Female sex showed a significant protective effect (HR 0.7, p=0.001). Adjusting the age-group cutoff from 25 to 55 years showed consistently high HRs for advanced age, without a distinct change at any point. Comparing HRs for T, N, and M stage between young and old patient subgroups showed that advanced disease increased the risk for DSS regardless of age, and was oftentimes a worse prognosticator in young patient groups.

Conclusions: The contribution of age at diagnosis to a patient's DSS is considerable, but there is no age cutoff that affords any unique risk-stratification in patients with DTC.

FIG. 1.

Contribution of age toward thyroid cancer-specific mortality. Covariates that were identical to those listed in Table 3 included: race, sex, tumor (T), nodal (N), metastasis (M) stage, and radioactive iodine therapy. Age was also a covariate, and this was incrementally stepped from 19–99 years. The hazard ratios (HRs) for age cutoffs from 25–59 are shown. The vertical axis represents the HR for the older age group, compared to the younger group. For example, the HR for an age cutoff of 45 years is 19.2. Regardless of the age cutoff chosen, the HR remains similar, with slight downsloping trend with increasing age. Ninety-five percent confidence intervals are shown as vertical whisker bars.

FIG. 2.

Contribution of oncologic characteristics toward thyroid cancer-specific mortality at different age cutoffs. Covariates were identical to those listed in Table 3. There are variable trends in hazard ratios across age subgroups. (A) T3 tumor status carries a uniformly worse prognosis (compared to T2 tumors) in younger versus older patient subgroups, regardless of the subgroup age cutoff. (B) N1b nodal disease (compared to N0 disease) carries a worse prognosis in younger patients than in older patients. This trend holds up until age 55 where we see opposite behavior: younger patients have better prognosis than their older counterparts. (C) Demonstrates change in prognostic implication for M1 disease (versus M0 disease) as patients are compared across various age cutoffs. For example, M1 disease carries a higher HR in patients under age 30 than in patients over age 30. At age cutoffs 40 and 45, M1 disease carries a higher HR in older patients. Above these cutoffs, younger patients' prognosis is worse again.

FIG. 3.

Kaplan-Meier plots comparing thyroid cancer-specific mortality in patients with metastatic disease. Patients are stratified at various age cutoffs (A, 35; B, 45, and C, 55 years). Top set of lines represent young patients (A: under age 35, B: under age 45, C: under age 55). Bottom set of lines represent the older patients (A: >35, B: >45, C: >55). 95% confidence intervals are denoted by the shaded regions. Vertical axis is proportion of survivors. Analysis time is in months.