Demographic and clinical characteristics
The demographic and clinical characteristics of 1,418 TC patients (645 males and 773 females) with initial distant metastases were displayed in Table 1. The median follow-up time was 8 months [interquartile range (IQR), 2–27]. PTC, FTC, MTC and ATC accounted for 43.51% (617/1418), 15.73% (223/1418), 7.19% (102/1418) and 19.25% (273/1418). Patients were divided into 5 groups: ≤55 years (25.39%, 360/1418), 56–65 years (23.55%, 334/1418), 66–75 years (26.02%, 369/1418), 76–85 years (18.90%, 268/1418), > 85 years (6.14%, 87/1418). In addition, 1,034 patients with initial lung metastasis accounted for 72.92% (1,034/ 1,418) and were further analyzed alone (Table 1). The overall TC-specific mortality rate was 49.58% (703/1418). Patients over 85 years had highest TC-specific mortality rate of (72/87), followed by patients of 76–85 years (58.96%, 158/268), 66–75 years (53.93%, 199/369), 56–65 years (46.71%, 156/334) and ≤ 55 years (32.78%, 118/360).
Table 1
The clinical characteristics of thyroid cancer with distant metastases (SEER database years of 2010–2017)
Characteristics | | Overall | ≤ 55 years | 56–65 years | 66–75 years | 76–85 years | > 85 years |
Number | | 1418 | 360 | 334 | 369 | 268 | 87 |
| N | % | N | % | N | % | N | % | N | % | N | % |
Gender | Male | 645 | 45.49 | 173 | 48.06 | 177 | 52.99 | 158 | 42.82 | 116 | 43.28 | 21 | 24.14 |
| Female | 773 | 54.51 | 187 | 51.94 | 157 | 47.01 | 211 | 57.18 | 152 | 56.72 | 66 | 75.86 |
Race | White | 1043 | 73.55 | 283 | 78.61 | 237 | 70.96 | 262 | 71.00 | 197 | 73.51 | 64 | 73.56 |
| Black | 155 | 10.93 | 32 | 8.89 | 45 | 13.47 | 42 | 11.38 | 24 | 8.96 | 12 | 13.79 |
| Others | 5 | 0.35 | 43 | 11.94 | 51 | 15.27 | 65 | 17.62 | 45 | 16.79 | 11 | 12.64 |
| Unknown | 215 | 15.16 | 2 | 0.56 | 1 | 0.30 | 0 | 0 | 2 | 0.75 | 0 | 0 |
Lymph node stage | N0 | 396 | 27.93 | 72 | 20.00 | 93 | 27.84 | 113 | 30.62 | 97 | 36.19 | 21 | 24.14 |
| N1a | 116 | 8.18 | 33 | 9.17 | 24 | 7.19 | 27 | 7.32 | 20 | 7.46 | 12 | 13.79 |
| N1b | 432 | 30.47 | 142 | 39.44 | 114 | 34.13 | 104 | 28.18 | 51 | 19.03 | 21 | 24.14 |
| N1NOS | 83 | 5.85 | 28 | 7.78 | 19 | 5.69 | 11 | 2.98 | 19 | 7.09 | 6 | 6.90 |
| NX | 141 | 9.94 | 13 | 3.61 | 28 | 8.38 | 51 | 13.82 | 36 | 13.43 | 13 | 14.94 |
| Unknown | 250 | 17.63 | 72 | 20.00 | 56 | 16.77 | 63 | 17.07 | 45 | 16.79 | 14 | 16.09 |
Extrathyroidal extension | Lung | 1034 | 72.92 | 253 | 70.28 | 222 | 66.47 | 283 | 76.69 | 207 | 77.24 | 69 | 79.31 |
| Bone | 543 | 38.29 | 134 | 37.22 | 156 | 46.71 | 143 | 38.75 | 85 | 31.72 | 25 | 28.74 |
| Brain | 88 | 6.21 | 26 | 7.22 | 25 | 7.49 | 16 | 4.34 | 18 | 6.72 | 3 | 3.45 |
| Liver | 160 | 11.28 | 40 | 11.11 | 38 | 11.38 | 40 | 10.84 | 36 | 13.43 | 6 | 6.90 |
Thyroid cancer specific mortality | Alive | 715 | 50.42 | 242 | 67.22 | 178 | 53.29 | 170 | 46.07 | 110 | 41.04 | 15 | 17.24 |
| Death | 703 | 49.58 | 118 | 32.78 | 156 | 46.71 | 199 | 53.93 | 158 | 58.96 | 72 | 82.76 |
Histology subtype | PTC | 617 | 43.51 | 208 | 57.78 | 145 | 43.41 | 152 | 41.19 | 95 | 35.45 | 17 | 19.54 |
| FTC | 223 | 15.73 | 36 | 10.00 | 53 | 15.87 | 73 | 19.78 | 48 | 17.91 | 13 | 14.94 |
| MTC | 102 | 7.19 | 36 | 10.00 | 40 | 11.98 | 11 | 2.98 | 13 | 4.85 | 2 | 2.30 |
| ATC | 273 | 19.25 | 51 | 14.17 | 61 | 18.26 | 82 | 22.22 | 56 | 20.90 | 23 | 26.44 |
| Others | 203 | 14.32 | 29 | 8.06 | 35 | 10.48 | 51 | 13.82 | 56 | 20.90 | 32 | 36.78 |
Thyroid cancer specific mortality | TC | 703 | 49.58 | 118 | 32.78 | 156 | 46.71 | 199 | 53.93 | 158 | 58.96 | 72 | 82.76 |
| PTC | 184 | 12.98 | 31 | 8.61 | 45 | 13.47 | 61 | 16.53 | 35 | 13.06 | 12 | 13.79 |
| FTC | 74 | 5.22 | 10 | 2.78 | 13 | 3.89 | 25 | 6.78 | 16 | 5.97 | 10 | 11.49 |
| MTC | 50 | 3.53 | 15 | 4.17 | 22 | 6.59 | 2 | 0.54 | 9 | 3.36 | 2 | 2.30 |
| ATC | 246 | 17.35 | 46 | 12.78 | 52 | 15.57 | 75 | 20.33 | 51 | 19.03 | 22 | 25.29 |
| Others | 149 | 10.51 | 16 | 4.44 | 24 | 7.19 | 36 | 9.76 | 47 | 17.54 | 26 | 28.89 |
Radiation therapy | | | | | | | | | | | | |
Radiation Beam or Radioactive implants | 425 | 29.97 | 105 | 29.17 | 113 | 33.83 | 121 | 32.79 | 64 | 23.88 | 22 | 25.29 |
Radioisotopes or Radiation beam plus isotopes or implants | 405 | 28.56 | 149 | 41.39 | 96 | 28.74 | 98 | 26.56 | 58 | 21.64 | 4 | 4.60 |
None or refused | 552 | 38.93 | 97 | 26.94 | 118 | 35.33 | 136 | 36.86 | 140 | 52.24 | 61 | 70.11 |
Unknown | 36 | 2.54 | 9 | 2.50 | 7 | 2.10 | 14 | 3.79 | 6 | 2.24 | 0 | 0.00 |
PTC, papillary thyroid cancer; FTC, follicular thyroid cancer; MTC, medullary thyroid cancer; ATC, anaplastic thyroid cancer; Others, other variants of thyroid cancer. According to the American Joint Committee on Cancer (AJCC) Staging Manual 7th Edition, lymph node category was classified into 5 groups as follows: no regional lymph node metastasis (N0); metastases to level VI [pretracheal, paratracheal, and prelaryngeal/Delphian lymph nodes] (N1a); metastasis to unilateral, bilateral, or contralateral cervical [LevelsⅠⅡⅢ Ⅳ or Ⅴ] or retropharyngeal or superior mediastinal lymph nodes [Level Ⅶ] (N1b); metastasis to regional lymph nodes but not otherwise specified (N1NOS); and regional lymph nodes cannot be assessed (NX). |
The association between age and TC-specific mortality in patients with distant metastases at diagnosis
In TC patients with distant metastases, the overall TC-specific mortality rate was 49.58% (703/1418), specifically, with number of 82.76% (72/87), 58.96% (158/268), 53.93% (199/369), 46.71% (156/334) and 32.78% (118/360) for patients aged > 85 years, 76–85 years, 66–75 years, 56–65 years and ≤ 55 years, respectively. Compared with patients ≤ 55 years, the crude HRs for patients with age of 56–65 years, 66–75 years, 76–85 years and > 85 years were 1.61(1.27–2.05, p < 0.001), 1.96 (1.56–2.46, p < 0.001), 2.43(1.91–3.09, p < 0.001) and 4.99(3.69–6.76, p < 0.001) (Table 2). After adjustments for tumor size, gender and radioactive therapy, the HRs were 1.69 (1.26–2.26, p < 0.001), 1.97 (1.47–2.64, p < 0.001), 2.18 (1.59–2.99, p < 0.001) and 3.24 (2.08–5.06, p < 0.001) for patients with age of 56–65 years, 66–75 years, 76–85 years and > 85 years. Compared with patients of 56–65 years, 66–75 years and 76–85 years, patients of > 85 years had crude HRs of 3.17(2.38–4.22, p < 0.001), 2.42(1.84–3.19, p < 0.001) and 1.99(1.50–2.64, p < 0.001), respectively. However, after adjustments for tumor size, gender and radioactive therapy, the HR remained significant only compared with patients of 56–65 years [1.83(1.20–2.78), p = 0.005] (Table 3).
Table 2
The association between age and thyroid cancer-specific mortality in patients with distant metastases
Variants | Mortality | Unadjusted | | Adjusteda | |
| n/N (%) | HR (95%CI) | p | HR (95%CI) | p |
TC | 703/1418(49.58) | | | | |
Age | ≤ 55 years | 118/360(32.78) | Ref. | | | |
| 56–65 years | 156/334(46.71) | 1.61(1.27–2.05) | < 0.001 | 1.69(1.26–2.26) | < 0.001 |
| 66–75 years | 199/369(53.93) | 1.96(1.56–2.46) | < 0.001 | 1.97(1.47–2.64) | < 0.001 |
| 76–85 years | 158/268(58.96) | 2.43(1.91–3.09) | < 0.001 | 2.18(1.59–2.99) | < 0.001 |
| > 85 years | 72/87(82.76) | 4.99(3.69–6.76) | < 0.001 | 3.24(2.08–5.06) | < 0.001 |
PTC | 184/617(29.82) | | | | |
Age | ≤ 55 years | 31/208(14.90) | Ref. | | | |
| 56–65 years | 45/145(31.03) | 2.22(1.41–3.51) | < 0.001 | 2.36(1.38–4.05) | < 0.001 |
| 66–75 years | 61/152(40.13) | 2.97(1.93–4.58) | < 0.001 | 3.00(1.76–5.10) | < 0.001 |
| 76–85 years | 35/95(36.84) | 3.28(2.00-5.37) | < 0.001 | 2.97(1.56–5.66) | 0.001 |
| > 85 years | 12/17(70.59) | 6.72(3.42–13.19) | < 0.001 | 1.68(0.48–5.85) | 0.416 |
FTC | 74/223(33.18) | | | | |
Age | ≤ 55 years | 10/36(27.78) | Ref. | | | |
| 56–65 years | 13/53(24.53) | 1.15(0.50–2.65) | 0.746 | 2.21(0.73–6.69) | 0.159 |
| 66–75 years | 25/73(34.25) | 1.43(0.68–2.08) | 0.346 | 2.79(1.08–7.18) | 0.034 |
| 76–85 years | 16/48(33.33) | 1.49(0.67–3.30) | 0.328 | 3.29(1.05–10.32) | 0.041 |
| > 85 years | 10/13(76.92) | 6.55(2.46–17.44) | < 0.001 | 22.80(3.95-131.78) | < 0.001 |
TC, thyroid cancer; PTC, papillary thyroid cancer; FTC, follicular thyroid cancer; HRs, hazard ratios; CI, confidence interval; a Adjusted for gender, tumor size, and radiation therapy; SEER database years of 2010–2017. |
Table 3
The association between age (> 55 years) and thyroid cancer-specific mortality in patients with distant metastases
Variants | Mortality | Unadjusted | | Adjusteda | |
| n/N (%) | HR (95%CI) | p | HR (95%CI) | p |
TC | 703/1418(49.58) | | | | |
Age | 56–65 years | 118/360(32.78) | Ref. | | | |
| > 85 years | 72/87(82.76) | 3.17(2.38–4.22) | < 0.001 | 1.83(1.20–2.78) | 0.005 |
| 66–75 years | 199/369(53.93) | Ref. | | | |
| > 85 years | 72/87(82.76) | 2.42(1.84–3.19) | < 0.001 | 1.40(0.93–2.09) | 0.104 |
| 76–85 years | 158/268(58.96) | Ref. | | | |
| > 85 years | 72/87(82.76) | 1.99(1.50–2.64) | < 0.001 | 1.48(0.99–2.21) | 0.058 |
PTC | 184/617(29.82) | | | | |
Age | 56–65 years | 45/145(31.03) | Ref. | | | |
| > 85 years | 12/17(70.59) | 3.11(1.63–5.90) | 0.001 | 0.94(0.28–3.16) | 0.913 |
| 66–75 years | 61/152(40.13) | Ref. | | | |
| > 85 years | 12/17(70.59) | 2.11(1.13–3.93) | 0.019 | 0.43(0.13–1.43) | 0.168 |
| 76–85 years | 35/95(36.84) | Ref. | | | |
| > 85 years | 12/17(70.59) | 2.16(1.12–4.17) | 0.022 | 0.95(0.27–3.31) | 0.933 |
FTC | 74/223(33.18) | | | | |
Age | 56–65 years | 13/53(24.53) | Ref. | | | |
| > 85 years | 10/13(76.92) | 5.16(2.21–12.08) | < 0.001 | 9.76(2.29–41.56) | 0.002 |
| 66–75 years | 25/73(34.25) | Ref. | | | |
| > 85 years | 10/13(76.92) | 4.91(2.28–10.55) | < 0.001 | 13.52(3.28–55.70) | < 0.001 |
| 76–85 years | 16/48(33.33) | Ref. | | | |
| > 85 years | 10/13(76.92) | 4.21(1.85–9.59) | 0.001 | 10.33(2.57–41.48) | 0.001 |
TC, thyroid cancer; PTC, papillary thyroid cancer; FTC, follicular thyroid cancer; HRs, hazard ratios; CI, confidence interval; a Adjusted for gender, tumor size, and radiation therapy; SEER database years of 2010–2017. |
In this cohort, lung was the most common site of metastasis, accounting for 72.92% (1,034/1,418). In these patients with lung metastasis, the overall TC-specific mortality rate was 55.03% (569/1034), with number of 85.51% (59/69), 62.32% (129/207), 60.78% (172/283), 54.05% (120/222) and 35.18% (89/253) for patients of > 85 years, 76–85 years, 66–75 years, 56–65 years and ≤ 55 years, respectively (Table 4). Compared with patients ≤ 55 years, the crude HRs for patients with age of 56–65 years, 66–75 years, 76–85 years and > 85 years were 1.75 (1.33–2.31, p < 0.001), 2.16 (1.67–2.80, p < 0.001), 2.45 (1.87–3.23, p < 0.001) and 4.96 (3.52–6.98, p < 0.001). After adjustments for tumor size, gender and radioactive therapy, the HRs were 1.68(1.20–2.36, p = 0.003), 2.18(1.57–3.02, p < 0.001), 2.16(1.51–3.08, p < 0.001) and 2.91(1.79–4.75, p < 0.001) for patients with age of 56–65 years, 66–75 years, 76–85 years and > 85 years. When compared with patients of 56–65 years, 66–75 years, and 76–85 years, patients of > 85 years had crude HRs of 2.94 (2.14–4.04, p < 0.001), 2.32 (1.72–3.14, p < 0.001) and 2.01(1.47–2.75, p < 0.001), respectively. After adjustments for tumor size, gender and radioactive therapy, the HR remained significant only compared with patients of 56–65 years [1.84(1.18–2.88), p = 0.007] (Table 5).
Table 4
The association between age and thyroid cancer-specific mortality in patients with lung metastasis
Variants | Mortality | Unadjusted | | Adjusteda | |
| n/N (%) | HR (95%CI) | p | HR (95%CI) | p |
TC | 569/1034(55.03) | | | | |
Age | ≤ 55 years | 89/253(35.18) | Ref. | | | |
| 56–65 years | 120/222(54.05) | 1.75(1.33–2.31) | < 0.001 | 1.68(1.20–2.36) | 0.003 |
| 66–75 years | 172/283(60.78) | 2.16(1.67–2.80) | < 0.001 | 2.18(1.57–3.02) | < 0.001 |
| 76–85 years | 129/207(62.32) | 2.45(1.87–3.23) | < 0.001 | 2.16(1.51–3.08) | < 0.001 |
| > 85 years | 59/69(85.51) | 4.96(3.52–6.98) | < 0.001 | 2.91(1.79–4.75) | < 0.001 |
PTC | 155/475(32.63) | | | | |
Age | ≤ 55 years | 25/161(15.53) | Ref. | | | |
| 56–65 years | 36/104 (34.62) | 2.35(1.41–3.92) | 0.001 | 2.54(1.38–4.66) | 0.003 |
| 66–75 years | 54/119(45.38) | 3.34(2.08–5.38) | < 0.001 | 3.31(1.82–6.01) | < 0.001 |
| 76–85 years | 31/79(39.24) | 3.37(1.96–5.79) | < 0.001 | 3.32(1.61–6.88) | 0.001 |
| > 85 years | 9/12(75.00) | 6.81(3.15–14.70) | < 0.001 | 2.39(0.66–8.65) | 0.183 |
FTC | 52/117(44.44) | | | | |
Age | ≤ 55 years | 8/17(47.06) | Ref. | | | |
| 56–65 years | 7/21(33.33) | 0.86(0.31–2.38) | 0.857 | 2.17(0.47–9.98) | 0.321 |
| 66–75 years | 19/44(43.18) | 1.08(0.47–2.50) | 0.861 | 3.95(1.15–13.63) | 0.030 |
| 76–85 years | 11/27(40.74) | 1.18(0.45–3.12) | 0.736 | 4.88(1.02–23.29) | 0.047 |
| > 85 years | 7/8(87.50) | 3.46(1.20–9.96) | 0.022 | * | 0.938 |
TC, thyroid cancer; PTC, papillary thyroid cancer; FTC, follicular thyroid cancer; HRs, hazard ratios; CI, confidence interval; a Adjusted for gender, tumor size, and radiation therapy; * due to the small sample size and relative high mortality in FTC patients of > 85 years, the HRs cannot be calculated; SEER database years of 2010–2017. |
Table 5
The association between age (> 55 years) and thyroid cancer-specific mortality in patients with lung metastasis
Variants | Mortality | Unadjusted | | Adjusteda | |
| n/N (%) | HR (95%CI) | p | HR (95%CI) | p |
TC | 480/781(61.46) | | | | |
Age | 56–65 years | 120/222(54.05) | Ref. | | | |
| > 85 years | 59/69(85.51) | 2.94(2.14–4.04) | < 0.001 | 1.84(1.18–2.88) | 0.007 |
| 66–75 years | 172/283(60.78) | Ref. | | | |
| > 85 years | 59/69(85.51) | 2.32(1.72–3.14) | < 0.001 | 1.22(0.79–1.88) | 0.381 |
| 76–85 years | 129/207(62.32) | Ref. | | | |
| > 85 years | 59/69(85.51) | 2.01(1.47–2.75) | < 0.001 | 1.44(0.92–2.24) | 0.107 |
PTC | 130/314(41.40) | | | | |
Age | 56–65 years | 36/104(34.62) | Ref. | | | |
| > 85 years | 9/12(75.00) | 2.84(1.36–5.90) | 0.005 | 1.03(0.30–3.51) | 0.958 |
| 66–75 years | 54/119(45.38) | Ref. | | | |
| > 85 years | 9/12(75.00) | 1.95(0.96–3.96) | 0.064 | 0.68(0.20–2.29) | 0.532 |
| 76–85 years | 31/79(39.24) | Ref. | | | |
| > 85 years | 9/12(75.00) | 2.13(1.01–4.51) | 0.047 | 1.18(0.33–4.24) | 0.797 |
FTC | 44/100(44.00) | | | | |
Age | 56–65 years | 7/21(33.33) | Ref. | | | |
| > 85 years | 7/8(87.50) | 3.89(1.36–11.13) | 0.011 | 23.14(2.18-245.47) | 0.009 |
| 66–75 years | 19/44(43.18) | Ref. | | | |
| > 85 years | 7/8(87.50) | 4.76(1.91–11.85) | 0.001 | 2.72(0.38–19.77) | 0.322 |
| 76–85 years | 11/27(40.74) | Ref. | | | |
| > 85 years | 7/8(87.50) | 3.78(1.43–10.02) | 0.007 | 8.71(1.76–43.22) | 0.008 |
TC, thyroid cancer; PTC, papillary thyroid cancer; FTC, follicular thyroid cancer; HRs, hazard ratios; CI, confidence interval; a Adjusted for gender, tumor size, and radiation therapy; SEER database years of 2010–2017. |
The association between age and PTC-specific mortality in patients with distant metastases at diagnosis
In PTC patients with initial distant metastases, the overall mortality rate was 29.82% (184/617), with number of 70.59% (12/17), 36.84% (35/95), 40.13% (61/152), 31.03% (45/145) and 14.90% (31/208) for patients of > 85 years, 76–85 years, 66–75 years, 56–65 years and ≤ 55 years, respectively (Table 2). Compared with patients ≤ 55 years, the crude HRs for patients of 56–65 years, 66–75 years, 76–85 years and > 85 years were 2.22(1.41–3.51, p < 0.001), 2.97(1.93–4.58, p < 0.001), 3.28(2.00-5.37, p < 0.001) and 6.72(3.42–13.19, p < 0.001) (Table 2). After adjustments for tumor size, gender and radioactive therapy, the HRs remained significant in patients aged 56–65 years [2.36(1.38–4.05), p < 0.001], 66–75 years [3.00 (1.76–5.10), p < 0.001] and 76–85 years [2.97(1.56–5.66), p = 0.001], but the HR of > 85 years group didn’t reach significancy because small number of patients.
In PTC patients, lung was also the most common site of metastasis, accounting for 76.99% (475/617). In these patients with lung metastasis, the overall PTC-specific mortality rate was 32.63%(155/475), with number of 75.00% (9/12), 39.24% (31/79), 45.38% (54/119), 34.62% (36/104), and 15.53% (15/161) for patients of > 85 years, 76–85 years, 66–75 years, 56–65 years and ≤ 55 years, respectively (Table 4). Compared with patients ≤ 55 years, the crude HRs for patients of 56–65 years, 66–75 years, 76–85 years, and > 85 years were 2.35(1.41–3.92, p = 0.001), 3.34(2.08–5.38, p < 0.001), 3.37(1.96–5.79, p < 0.001) and 6.81(3.15–14.70, p < 0.001) (Table 4). After adjustments for tumor size, gender and radioactive therapy, the HRs remained significant for patients of 56–65 years [2.54(1.38–4.66), p = 0.003], 66–75 years [3.31(1.82–6.01), p < 0.001] and 76–85 years [3.32(1.61–6.88), p = 0.001], but the HR of > 85 years group didn’t reach significancy because small number of patients.
Kaplan-Meier analyses of TC-specific survival of TC patients with lung metastasis
In TC patients with distant metastases, TC-specific survival curves decreased significantly with the increase of age (Log Rank p < 0.001) (Fig. 1A), and the survival curve of patients over 85 years has an obvious decline with the worst prognosis. Similar results were observed in PTC (Fig. 1B) and FTC (Fig. 1C). There was no significant survival difference among all age groups in ATC patients (Fig. 1D).
In TC patients with lung metastasis, the TC-specific survival curves also decreased significantly as age of patients increased (Log Rank p < 0.001) (Fig. 2A). Similar results could be observed in PTC (Fig. 2B) and FTC (Fig. 2C), and the increased age had no significant impact on the survival of ATC patients (Fig. 2D). The survival curve of patients over 85 years showed a sharp decrease and similar trends could also be observed when we further divided patients in to 4 groups (71–75 years, 76–80 years, 81–85 years and > 85 years) (Supplemental Fig. 1A, 1B and 1C). Still, increased age had no significant impact on survival of ATC patients (Supplemental Fig. 1D).