The Prognostic Impact of Tumor Size in Papillary Thyroid Carcinoma is Modified by Age

BACKGROUND: Although the importance of tumor size in papillary thyroid cancer (PTC) is well established, there is no research investigating whether age modifies the impact of tumor size, and there is conflicting evidence regarding optimal size thresholds for prognostic discrimination. We aimed to verify that tumor size is an independent prognostic factor in PTC, investigate the impact of patient age, and identify optimal size cutoffs for risk stratification using objective measures of model performance. METHODS: A retrospective analysis of 574 patients with PTC, using multivariate Cox regression models to test the impact of tumor size on recurrence-free survival (RFS). Subgroup analyses were performed in patients aged <55 and ≥55 years. Exploratory analyses to identify optimal size cutoffs for prognostic discrimination were performed using the proportion of variation explained (PVE) and Harrell's C-index. RESULTS: Tumor size predicted RFS on multivariate analysis in the overall study cohort (hazard ratio [HR] 1.16; [95% confidence interval (CI)1.01-1.34]; p = 0.038). In subgroup analysis, there was no association between tumor size and RFS in patients aged <55 years (HR 1.11; [CI 0.89-1.38]; p = 0.362). In contrast, size was an independent predictor of RFS in patients aged ≥55 years (HR 1.52; [CI 1.11-2.07]; p = 0.009). In this subgroup, an optimal size threshold of >2 cm versus ≤2 cm (HR 5.24; [CI 2.30-11.92]; p < 0.001; PVE: 36%; C-index: 0.66) provided the greatest prognostic discrimination. There was no incremental improvement in prognostic value by further stratification of size. CONCLUSION: In our PTC cohort, the impact of tumor size on RFS was limited to patients aged ≥55 years. A single size threshold of 2 cm maximized prognostic discrimination with tumors >2 cm associated with a five times higher risk of recurrence than those ≤2 cm. These findings need to be validated in independent large cohorts and the potential management and staging implications further studied.