Effect of Tumor Size on Risk of Metastatic Disease and Survival for Thyroid Cancer: Implications for Biopsy Guidelines

Background: In many risk-stratification systems, the decision to biopsy thyroid nodules is determined by their sonographic features and size. Nevertheless, even low-suspicion nodules are often biopsied at small size thresholds because it is assumed that larger malignant nodules are associated with poorer outcomes. The aim of this study was to quantify the effect of thyroid cancer tumor size on survival and risk of T4 stage, nodal disease, and distant metastases. Methods: The Surveillance, Epidemiology, and End Results 18 database was queried to obtain tumor size, staging information, and survival data for cases of differentiated thyroid cancer (DTC) and non-DTC reported between 2004 and 2014. Observed probabilities of tumor extent at diagnosis, including regional nodal disease and distant metastases, as a function of size and tumor histology were estimated for thyroid cancers measuring between 1 and 150 mm. A multivariate Cox regression model was used to describe all-cause mortality as a function of patient and tumor characteristics, and the functional dependence of mortality on size was computed. Results: A total of 112,128 patients were analyzed, with 67% having thyroid cancers >= 1 cm, and 29% >= 2.5 cm. For DTC tumors <4 cm, the risk of local invasion, nodal metastases, or distant metastases was low, and there was no size threshold associated with a sharp rise in adverse outcomes. For DTC tumors <4 cm, the probability of distant metastases was <3%. Older age, male sex, non-DTC histology, T4 stage, and regional and distant metastatic disease increased the all-cause mortality rate. Tumor size did not increase the mortality rate above baseline until tumors were >2.5 cm. Conclusion: Increasing tumor size does not affect survival until a threshold of 2.5 cm. Since the dimension of nodules on ultrasound has been shown to be larger than their size at gross pathology, these findings suggest that recommended size thresholds to biopsy low-suspicion thyroid nodules can be increased.