A meta-analysis examining the independent association between thyroid nodule size and malignancy

Background: Tumor size is recognized as an important predictor of malignancy in many types of cancers. However, there is no clear line of characterization when it comes to the association between thyroid nodule size and malignancy risk prediction; and the current data remains inconsistent across different studies. The aim of our study is to examine the association between nodule size and malignancy using meta-analysis of the current literature. Methods: Data sources were gathered through systemic search of PubMed, Embase and other scientific databases for articles published between January 1, 1996 and June 1, 2013. A reference group with nodule sizes < 3 cm was set as a control group. Two other nodule size categories were established and these included nodules from 3-5.9 cm and nodules ≥6 cm in size. Primary outcome was a histologically proven malignancy per nodule size category. The effect sizes of clinicopathologic parameters, which are the quantitative measures of association strength between two variables, were calculated by the means of odds ratios (OR). The effect sizes were then combined using a random-effects model. Results: Seven studies met our inclusion criteria with 10,817 thyroid nodules evaluated. Malignancy was identified in 2,206 (20.4%) nodules. After adjusting for patient age and gender, nodules that measured 3-5.9 cm had a 26% greater malignancy risk compared to those measuring <3 cm [OR, 1.26; 95% confidence interval (CI): 1.13-1.39]. However, nodules 6 cm or larger had a 16% lower risk of malignancy compared to those measuring < 3 cm (OR, 0.84; 95% CI: 0.73-0.98). Conclusions: Thyroid nodule size predicts cancer risk. However, a threshold effect of thyroid nodule size 6 cm or greater is significantly associated with a more benign disease.