Synergistic effects of histologic subtype, T-stage, and M-stage in the prognosis of differentiated thyroid cancer: a retrospective observational study

BACKGROUND: The incidence of differentiated thyroid cancer has increased in many countries during the past few decades. This study aimed to investigate the synergistic effect of clinicopathological factors, including histologic subtype, T stage, and M stage, on the prognosis of differentiated thyroid cancer (DTC). METHODS: We collected data on 86,302 patients with DTC from 2004 to 2013 from the SEER database. We extracted multiple variables from the selected object of study. Demographic characteristics consisted of age at diagnosis, sex, year of diagnosis, and race. Pathological characteristics included T stage, N stage, M stage, multifocality, histologic subtype and extrathyroidal extension. Treatment characteristics included radiation therapy and surgery. Univariate and multivariate analyses were conducted to evaluate the correlation between clinicopathological factors and prognosis. The relative excess risk of synergistic effect (RERI), attributable proportion (AP) of synergistic effect, and synergy index (SI) were used to explore the synergistic effect of these factors on prognosis. RESULTS: Histologic subtype, T-stage, and M-stage were found to be risk factors for cancer-specific survival and all-cause survival in multivariate analysis. The cancer-specific mortality (CSM) rates per 1,000 person-years for patients were found to be higher in follicular thyroid carcinoma (FTC) patients and patients with T3–T4, M1 status disease. In addition, CSM and all-cause mortality (ACM) were also associated with age, sex, race, N- stage, extension, radiation treatment, and surgical approach (all, P<0.001). We also found that histologic subtype had a synergistic effect with both T and M status stage on the prognosis (RERI =7.431, AP =0.278, SI =1.407; RERI =37.889, AP =0.430, SI =1.771, respectively). Synergy was also noted between T- stage and M- stage (RERI =134.125, AP =0.537, SI =2.168). CONCLUSIONS: Histologic subtype, T-stage, and M-stage in different combinations were risk factors for poor prognosis in DTC, and had synergistic effects.