Objective. To evaluate survival trends and differences in a large cohort of patients with stage IV differentiated thyroid cancer treated with radioactive iodine (RAI), external beam radiation therapy (EBRT), or no radiation following surgery.
Design. Multicenter retrospective cohort study using data from the National Cancer Database (NCDB) from 2002–2012.
Setting and participants. The study group consisted of a random sample of all inpatient discharges with a diagnosis of differentiated thyroid cancer (DTC). This yielded a cohort of 11,832 patients with stage IV DTC who underwent primary surgical treatment with thyroidecromy. Patients were stratified by cancer histology into follicular thyroid cancer (FTC) and papillary thyroid cancer (PTC). Patients were additionally stratified into 3 substage groups: IV-A, IV-B, and IV-C. Administrative censoring was implemented at 5 and 10 year marks of survival time.
Main outcome measures. The primary outcome was all-cause mortality. Survival was analyzed at 5 and 10 years. Multivariate analysis was performed on a number of covariates including age, sex, race, socioeconomic status, TNM stage, tumor grade, surgical length of stay, and surgical treatment variables such as neck dissection and lymph node surgery.
Main results. Most patients (91.24%) had PTC and 8.76% had FTC. The average age of patients in the RAI group was younger (FTC, age 66; PTC, age 58) than patients in the EBRT (FTC, age 69; PTC, age 65) or no RT groups. (FTC, age 73; PTC, age 61). In contrast to FTC patients, a large majority of PTC patients underwent surgical neck dissection. There were no significant differences in sex, ethnicity, primary payer, median income quartile, or education level among the 3 groups for patients with FTC. However, in PTC there was a majority of female and ethnically white/Caucasian patients in all 3 groups. In addition, patients with PTC who did not receive RT or received RAI were more likely to have private insurance versus those who underwent EBRT, who were more often covered under Medicare. These differences in primary payer were statistically significant (P < 0.001).
Statistically significant differences in mortality were observed at 5 and 10 years in both papillary and follicular thyroid cancer among the 3 groups. In the PTC groups, patients treated with EBRT had the highest mortality rates (46.6% at 5 years, 50.7% at 10 years), while patients with PTC receiving no RT had lower mortality rates (22.7% at 5 years, 25.5% at 10 years), and PTC patients receiving RAI had the lowest mortality rates (11.0% at 5 years, 14.0% at 10 years). Similar results were seen in patients with FTC, in which patients treated with EBRT had the highest mortality rates (51.4% at 5 years, 59.9% at 10 years), while patient with FTC receiving no RT had lower mortality rates (45.5% at 5 years, 51% at 10 years), and FTC patients receiving RAI had the lowest mortality rates (29.2% at 5 years, 36.8% at 10 years).
Using univariate analysis, EBRT showed a statistically significant increase in 5- and 10-year mortality for patients with PTC stage IV-A and IV-B as compared with no radiation. This was demonstrated in both stage IV-A and IV-B subgroups at 5 years (EBRT 5-year HR PTC stage IV-A = 2.04, 95% confidence interval [CI] 1.74–2.39, P < 0.001; EBRT 5-year HR PTC stage IV-B = 2.23, 95% CI 1.42–3.51, P < 0.001; and 10 years [EBRT 10-year HR PTC stage IV-A = 2.12, 95% CI 1.79-2.52 P < 0.001; EBRT 10-year HR PTC stage IV-B = 2.03, 95% CI 1.33-3.10, P < 0.001). RAI showed a statistically significant decrease in 5- and 10-year mortality in both PTC and FTC compared with no radiation, regardless of pathologic sub-stage. The largest reduction in risk was seen in FTC stage IV-B patients at 5 years [RAI 5 year HR FTC stage IV-B = 0.31, 95% CI 0.12-0.80, P < 0.05). Multivariate analysis was also performed and showed similar results to univariate analysis except that there was no longer a statistically significant difference in EBRT versus no RT in stage IV-A PTC at 5 and 10 years (EBRT 5-year HR PTC stage IV-A = 1.2, 95% CI 0.91–1.59, EBRT 10-year HR PTC stage IV-A = 1.29, 95% CI 0.93–1.79). Reductions in death hazard seen in all groups treated with RAI versus no RT previously observed in univariate analysis remained statistically significant in all groups on multivariate analysis.
Multivariate analysis revealed a number of significant covariates. Increase in age was noted to be associated with higher death hazard in all groups except FTC stage IV-B and stage IV-C. Every additional year of age increased the hazard of death by ~2% to 5%, up to a maximum of 9% per year. Females overall had a lower hazard of death compared with their male counterparts, most notably in PTC. African-American patients had improved survival in FTC (5 years) but lower survival in PTC (5 and 10 years) as compared with white patients. Tumor grade showed a dose response in models studied, with increasing death hazards with worsening tumor differentiation.