Baseline Features
Between 1973–2015, a total of 1642 patients were diagnosed with ATC in the SEER database. 349 patients were excluded from this study because of their survival months were less than 1 month or unknown. Finally, a total of 1293 patients were enrolled in the study, including 495 male (38.3%) and 798 female (61.7%) patients. The female to male ratio is 1.6/1. The median age at diagnosis was 70.0 years (range 15–99) with no significant differences between sexuality. The mean tumor size was 60.0 mm (Range; 0–996 mm), however, 31.0% patients (n = 401) had missing information on this variable. Patients’ characteristics are shown in Table 1. The cohort was divided into four subgroups according to the year of diagnosis by every ten years.
Table 1
Patients’ characteristics
Characteristics (patients eligible for analysis) | N (%) |
Sex Female Male | 798(61.7) 495(38.3%) |
Median age Median tumour size (mm) ≤ 60 > 60 Stage IVA IVB IVC Surgery performed not performed Radiation performed None/Unknown Years of diagnosis 1976–1985 1986–1995 1996–2005 2006–2015 | 70.0 60.0 466 426 80 494 645 680 597 867 426 73 122 389 709 |
Atc Survival
Stage-related trends
Among the 1293 eligible patients, the median OS was 4 months (95% confidence interval [CI]: 3.718–4.282). The median CSS is 5 months (95% CI:4.507–5.493). The 5-year OS for Stage IVA, B and C were 26.6%, 11.7% and 2.5%, respectively. The 5-year CSS for the same respective stage were 43.5%, 22.3% and 4.9%. The median OS for stage IVA, B and C are 9, 6 and 3 months (95% CI: 4.275–13.725, 5.126–6.874, 2.777–3.223, respectively). The median CSS was 38, 8 and 4 months (95% CI: 4.086–71.914, 6.905–9.095, 3.609–4.391, respectively) for the same respective stage. ATC patients with distant metastasis (Stage IVC) had poor prognosis (CSS: (χ2 = 150.088, P < 0.001 for log-rank test) (Fig. 1a and 1b).
Years-related Trends
We used the SEER18 cohort to compare the improvement in survival over the past 40 years. The cohort was divided into four subgroups according to the year of diagnosis by every ten years.
Using diagnosis year 1976–1985 as reference, the OS of the next 3 decades were not significant improved (χ2 = 0.077, 0.890, 0.212; P = 0.782, 0.345, 0.645) (Fig. 2a). The 5-year OS for patients diagnosed in 1976–1985, 1986–1995, 1996–2005 and 2006–2015 was 6.3%, 5.7%, 10.0% and 7.4%, respectively. The median OS was 4, 3, 4 and 4 months (95% CI: 2.931–5.069, 2.228–3.772, 3.460–4.540, 3.566–4.434, respectively) for the same respective time periods. The difference in OS for patients with stage IVB and stage IVC in recent decades were not statistical significance. (χ2 = 0.458, 2.917, 1.589; P = 0.498, 0.088, 0.207 for Stage IVB; χ2 = 2.454, 0.277, 0.421; P = 0.117, 0.598, 0.517 for Stage IVC) (Fig. 2b and 2c).
However, the CSS were improved in the recent decades and the difference reached statistical significance. (χ2 = 13.608, P = 0.003 for log-rank test) (Fig. 2d). The 5-year CSS was 10.0%, 9.5% ,18.4%, 16.5% for patients diagnosed among 1976–1985, 1986–1995, 1996–2005, 2006–2015. The Median CSS was 4, 4, 6 and 6 months (95% CI: 2.947–5.053, 3.151–4.849, 5.024–6.976, 5.261–6.739, respectively) for the same respective time periods. There was obvious improvement in survival for patients at stage IVB and stage IVC, and the differences were statistically significant. (stage IVB: χ2 = 12.987, P = 0.005, stage IVC: χ2 = 21.992, P < 0.001 for log-rank test) (Fig. 2e and 2f). The median CSS for patients diagnosed with stage IVB in 1976–1985, 1986–1995, 1996–2005 and 2006–2015 was 5, 7, 10 and 8 months (95% CI: 2.985–7.015, 3.461–10.539, 5.602–14.398, 6.619–9.381, respectively). The median CSS for patients diagnosed with Stage IVC for the same respective time periods was 3, 2, 3 and 4 months. (95% CI: 1.853–4.147, 1.222–2.778, 2.294–3.706, 3.336–4.664, respectively).
Surgery-related Trends
Surgery was related to an improved survival. The patients who received surgery had better OS and CSS than those who did not receive surgery (OS: χ2 = 105.303, P < 0.001, CSS: χ2 = 84.033, P < 0.001 for log-rank test) (Fig. 3a and 3b). The survival benefit was only observed in Stage IVB (OS: χ2 = 43.887, P < 0.001, CSS: χ2 = 27.301, P < 0.001 for log-rank test) (Fig. 4a and 4b) and C (OS: χ2 = 16.399, P < 0.001, CSS: χ2 = 12.521, P < 0.001 for log-rank test) (Fig. 4c and 4d) instead of Stage IVA (OS: χ2 = 3.651, P = 0.056) (Fig. 4e). The 5-year OS for patients with and without surgery is 12.3% and 3.2%. The median OS of patients with or without surgery is 6 months and 3 months (95% CI: 5.299–6.701, 2.754–3.246, respectively). The 5-year CSS of patients with or without surgery is 22.5% and 8.1% respectively. The median CSS of patients with surgery is 8 months and that of patients without surgery is 4 months (95% CI: 7.064–8.936, 3.591–4.409, respectively).
Radiotherapy-related Trends
Adoption of radiotherapy was associated with an improved survival (Fig. 5a and 5b). The OS for patients who received radiotherapy were superior to those who did not receive radiotherapy (χ2 = 51.402, P < 0.001 for log-rank test). The OS benefit was observed in all different stage (stage IVA: χ2 = 7.346, P = 0.007 for log-rank test, stage IVB: χ2 = 37.491, P < 0.001 for log-rank test,stage IVC: χ2 = 23.208, P < 0.001 for log-rank test) (Fig. 6a, 6b and 6c). The 5-year OS for patients with and without radiotherapy is 9.6% and 4.7% respectively. The median OS for patients with radiotherapy is 5 months and that of patients without radiotherapy is 2 months (95% CI: 4.561–5.439, 1.631–2.369, respectively). The CSS for patients with radiotherapy were also better than patients without radiotherapy (χ2 = 22.958, P < 0.001 for log-rank test). However, for patients with Stage IVA, the benefit was not statistically significant (χ2 = 2.067, P = 0.151 for log-rank test) (Fig. 6d). The CSS benefit was observed in Stage IVB (χ2 = 18.717, P < 0.001 for log-rank test) and C (χ2 = 12.615, P < 0.001 for log-rank test) (Fig. 6e and 6f). The 5-year CSS of patients with and without radiotherapy is 17.1% and 13.7%. The Median CSS of patients with radiotherapy is 6 months and that of patients without radiotherapy is 4 months (95% CI: 5.367–6.633, 3.351–4.649, respectively).
Combined Surgery And Radiotherapy For Stage Iva
The above analysis data shows that patients with stage IVA have not obtained CSS improvement from surgery or radiotherapy alone. Therefore, we further analyzed the effect of combined surgery and radiotherapy on the survival of patients with stage IVA. The results showed that compared with patients with stage IVA who received surgery alone, the survival of patients who received surgery and radiotherapy combined treatment was significantly improved (OS: χ2 = 6.454, P = 0.011 for log-rank test) (Fig. 7). The median OS of patients with stage IV A receiving surgery, radiotherapy alone and the combination of the two is 4, 5 and 33 months (95% CI: 0.411–7.589, 0.000-10.500, 16.290–49.710, respectively).