Innovative analysis of distant metastasis in differentiated thyroid cancer

Differentiated thyroid cancer (DTC) is the most common thyroid cancer with a relatively high survival rate. The association between certain risk factors of distant metastasis (DM) remains uncertain. In order to assess the prognosis of patients with DTC better, the present study aimed to investigate the synergistic effects between histologic subtype, tumor size, lymph node metastasis (LNM) status and extrathyroidal extension (ETE) on the incidence of DM in DTC. Data of 96,788 patients with DTC were obtained from the Surveillance, Epidemiology and End Results database. The association between clinicopathological factors and DM was evaluated by univariate and multivariate analyses. The synergistic effects of relevant factors were determined by measuring the relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP) and synergy index (SI). The results demonstrated that tumor size, LNM status, histologic subtype and ETE were independent risk factors for DM [odds ratio (OR)=2.433; P<0.001; OR=3.998; P<0.001; OR=6.266; P<0.001; and OR=3.873; P<0.001, respectively]. In addition, a significant additive synergistic effect on DM was identified between ETE and histologic subtype, ETE and LNM status, as well as between ETE and tumor size (RERI=34.097; AP=0.706; SI=3.585; RERI=6.425; AP=0.410; SI=1.781; and RERI=76.973; AP=0.864; SI=7.930, respectively). Therefore, the results of this study revealed that ETE with follicular thyroid histology, N1 stage or large tumor size may have a synergistic effect on the risk of DM in patients with DTC. These results suggested that individualized treatment may benefit patients with DTC, and when ETE coexists with one of the identified risk factors, radical treatments may be required.