Clinicopathological characteristics of patients
A total of 58424 patients were enrolled in this study, among which 32025 (54.8%) were married and 26399 (45.2%) were unmarried. Detailed demographic and clinicopathological characteristics are shown in Table 1, and these characteristics are stratified by marital status. Chi-square tests demonstrated significant differences in most of the other variables between different marital status, including gender (P < 0.001), race (P < 0.001), histology (P < 0.001), grade (P < 0.001), stage (P = 0.016), surgery of primary site (P < 0.001), intraoperative lymph node evaluation (P < 0.001), and chemotherapy (P < 0.001). Additionally, clinicopathological characteristics comparison by the single, separated, divorced and widowed patients within unmarried group were shown in Supplementary Table 1.
Table 1
Clinicopathological characteristics of NSCLC patients in SEER database before propensity score matching
Variable
|
Total
|
Married
|
Unmarried
|
P value
|
|
(n = 58424)
|
(n = 32025,54.8%)
|
(n = 26399,45.2%)
|
|
Gender
|
|
|
|
P<0.001
|
Male
|
30296(51.9%)
|
19319(60.3%)
|
10977(41.6%)
|
|
Female
|
28128(48.1%)
|
12706(39.7%)
|
15422(58.4%)
|
|
Age
|
|
|
|
P = 0.386
|
≤ 65
|
23146(39.6%)
|
12636(39.5%)
|
10510(39.8%)
|
|
༞65
|
35278(60.4%)
|
19389(60.5%)
|
15889(60.2%)
|
|
Race
|
|
|
|
P<0.001
|
White
|
47010(80.5%)
|
26470(82.7%)
|
20540(77.8)
|
|
Black
|
6710(11.5%)
|
2372(7.4%)
|
4338(16.4%)
|
|
Other
|
4707(8.1%)
|
3183(9.9%)
|
1521(5.8%)
|
|
Histology
|
|
|
|
P<0.001
|
ADC
|
35374(60.5%)
|
19863(62.0%)
|
15511(58.8%)
|
|
SCC
|
20585(35.2%)
|
10821(33.8%)
|
9764(37.0%)
|
|
LCC
|
1215(2.1%)
|
628(2.0%)
|
587(2.2%)
|
|
ASC
|
1250(2.1%)
|
713(2.2%)
|
537(2.0%)
|
|
Grade
|
|
|
|
P<0.001
|
Well differentiated
|
6572(11.2%)
|
3770(11.8%)
|
2802(10.6%)
|
|
Moderately differentiated
|
23324(39.9%)
|
12918(40.3%)
|
10406(39.4%)
|
|
Poorly differentiated
|
27581(47.2%)
|
14849(46.4%)
|
12732(48.2%)
|
|
Undifferentiated
|
947(1.6%)
|
488(1.5%)
|
459(1.7%)
|
|
Stage
|
|
|
|
P = 0.016
|
I
|
19051(32.6%)
|
10586(33.0%)
|
8483(32.1%)
|
|
II
|
7817(13.4%)
|
4339(13.5%)
|
3478(13.2%)
|
|
III
|
12899(22.1%)
|
7047(22.0%)
|
5852(22.2%)
|
|
IV
|
18657(31.9%)
|
10071(31.4%)
|
8586(32.5%)
|
|
Surgery of primary site
|
|
|
|
P<0.001
|
No
|
31304(53.6%)
|
16096(50.3%)
|
15208(57.6%)
|
|
Yes
|
27120(46.4%)
|
15929(49.7%)
|
11191(42.4%)
|
|
Intraoperative lymph node evaluation
|
|
|
|
P<0.001
|
No
|
30865(52.8%)
|
15809(49.4%)
|
15056(57.0%)
|
|
Yes
|
27559(47.2%)
|
16216(50.6%)
|
11343(43.0%)
|
|
Chemotherapy
|
|
|
|
P<0.001
|
No
|
32318(55.3%)
|
16696(52.1%)
|
15622(59.2%)
|
|
Yes
|
26106(44.7%)
|
15329(47.9%)
|
10777(40.8%)
|
|
Radiotherapy
|
|
|
|
P = 0.198
|
No
|
35966(61.6%)
|
19790(61.8%)
|
16176(61.3%)
|
|
Yes
|
22458(38.4%)
|
12235(38.2%)
|
10223(38.7%)
|
|
ADC Adenocarcinoma, SCC Squamous cell carcinoma, LCC Large Cell Carcinoma, ASC Adenosquamous carcinoma |
Survival Analysis
Before PSM, the married group had significantly better OS and CSS outcomes than the unmarried group (OS median survival (95% CI): 26 (26–27) vs. 20 (19–20) months, P < 0.001; CSS median survival (95% CI): 32 (31–34) vs. 24 (24–25) months, P < 0.001). Within the unmarried group, patients who were divorced had better OS (median survival (95% CI): 21 (20–23) months) compared to those who were single (median survival (95% CI): 19 (18–20) months, p < 0.001) or widowed (median survival (95% CI): 20 (19–20) months, p < 0.001). In addition, single patients had worse CSS (median survival (95% CI): 22 (21–24) months) than divorced patients (median survival (95% CI): 26 (25–28) months, p < 0.001) or widowed patients (median survival (95% CI): 25 (24–26) months, p = 0.016) (Fig. 1).
Since most clinicopathological characteristics between married and unmarried groups were significantly different, PSM was performed to balance potentially confounding factors. The married group was matched at a 1:1 ratio with the unmarried group. After matching, 20148 pairs were selected into further analysis, and all clinicopathological characteristics between the married and unmarried groups were well balanced without significant difference, as examined by chi-square tests (Table 2 and Supplementary Fig. 1).
Table 2
Clinicopathological characteristics of NSCLC patients in SEER database after propensity score matching
Variable
|
Total
|
Married
|
Unmarried
|
P value
|
|
(n = 40296)
|
(n = 20148,50.0%)
|
(n = 20148,50%)
|
|
Gender
|
|
|
|
P = 0.952
|
Male
|
19210(47.7%)
|
9608(47.7%)
|
9602(47.7%)
|
|
Female
|
21086(52.3%)
|
10540(52.3%)
|
10546(52.3%)
|
|
Age
|
|
|
|
P = 0.871
|
≤ 65
|
16622(41.2%)
|
8303(41.2%)
|
8319(41.3%)
|
|
༞65
|
40296(58.8%)
|
11845(58.8%)
|
11829(58.7%)
|
|
Race
|
|
|
|
P = 0.721
|
White
|
33888(84.1%)
|
16954(84.1%)
|
16934(84.0%)
|
|
Black
|
4010(10.0%)
|
1984(9.8%)
|
2026(10.1%)
|
|
Other
|
2398(6.0%)
|
1210(6.0%)
|
1188(5.9%)
|
|
Histology
|
|
|
|
P = 0.966
|
ADC
|
24913(61.8%)
|
12444(61.8%)
|
12469(61.9%)
|
|
SCC
|
14131(35.1%)
|
7070(35.1%)
|
7061(35.0%)
|
|
LCC
|
635(1.6%)
|
320(1.6%)
|
315(1.6%)
|
|
ASC
|
617(1.5%)
|
314(1.6%)
|
303(1.5%)
|
|
Grade
|
|
|
|
P = 0.986
|
Well differentiated
|
4309(10.7%)
|
2143(10.6%)
|
2166(10.8%)
|
|
Moderately differentiated
|
16234(40.3%)
|
8119(40.3%)
|
8115(40.3%)
|
|
Poorly differentiated
|
19302(47.9%)
|
9661(48.0%)
|
9641(47.9%)
|
|
Undifferentiated
|
451(1.1%)
|
225(1.1%)
|
226(1.1%)
|
|
Stage
|
|
|
|
P = 0.993
|
I
|
13348(33.1%)
|
6665(33.1%)
|
6683(33.2%)
|
|
II
|
5191(12.9%)
|
2591(12.9%)
|
2600(12.9%)
|
|
III
|
8569(21.3%)
|
4285(21.3%)
|
4248(21.3%)
|
|
IV
|
13188(32.7%)
|
6607(32.8%)
|
6581(32.7%)
|
|
Surgery of primary site
|
|
|
|
P = 0.811
|
No
|
21576(53.5%)
|
10776(53.5%)
|
10800(53.6%)
|
|
Yes
|
18720(46.5%)
|
9372(46.5%)
|
9348(46.4%)
|
|
Intraoperative lymph node evaluation
|
|
|
|
P = 0.992
|
No
|
21309(52.9%)
|
10655(52.9%)
|
10654(52.9%)
|
|
Yes
|
18987(47.1%)
|
9493(47.1%)
|
9494(47.1%)
|
|
Chemotherapy
|
|
|
|
P = 0.904
|
No
|
22420(55.6%)
|
11216(55.7%)
|
11204(55.5%)
|
|
Yes
|
17876(44.4%)
|
8932(44.3%)
|
8944(44.4%)
|
|
Radiotherapy
|
|
|
|
P = 0.821
|
No
|
25162(62.4%)
|
12592(62.5%)
|
12570(62.4%)
|
|
Yes
|
15134(37.6%)
|
7556(37.5%)
|
7578(37.6%)
|
|
ADC Adenocarcinoma; SCC Squamous cell carcinoma; LCC Large Cell Carcinoma; ASC Adenosquamous carcinoma |
After PSM, the married group consistently demonstrated better OS and CSS outcomes than unmarried group (OS median survival (95% CI): 25 (24–26) vs. 22 (21–23) months, P < 0.001; CSS median survival (95% CI): 31 (30–32) vs. 27 (26–28) months, P < 0.001). Similarly, within the unmarried group, the divorced patients had better OS (median survival (95% CI): 23 (22–24) months) than single patients (median survival (95% CI): 20 (19–22) months, P = 0.006). Additionally, single patients had worse CSS (median survival (95% CI): 24 (23–25) months) than divorced patients (median survival (95% CI): 28 (26–30) months, p = 0.003) or widowed patients (median survival (95% CI): 30 (28–33) months, p < 0.001) (Fig. 2).
Cox Proportional Hazards Regression Model
To further explore whether different marital statuses had different impact on OS and CSS, we analysed all related variables, including marital status, with a Cox proportional hazards regression model. In univariable analysis, single patients had significantly worse OS (HR (95% CI): 1.047 (1.009–1.087), P = 0.015) and CSS (HR (95% CI): 1.045 (1.004–1.087), P = 0.031) than married patients, and so did the divorced patients compared to married patients (OS: HR (95% CI): 1.125 (1.085–1.166), P < 0.001; CSS: HR (95% CI): 1.131 (1.089–1.175), P < 0.001). In addition, the widowed patients were associated with worse OS compared to married patients (HR (95% CI): 1.093 (1.056–1.132), P < 0.001). We also performed multivariable Cox proportional hazards regression analysis. And all subgroups but separated patients within unmarried group had significantly worse survival compared to married group (OS: single (HR (95% CI): 1.085 (1.046–1.126), P < 0.001), separated (HR (95% CI): 1.137 (1.019–1.270), P = 0.022), divorced (HR (95% CI): 1.148 (1.106–1.192), P < 0.001) and widowed (HR (95% CI): 1.139 (1.099–1.181), P < 0.001); CSS: single (HR (95% CI): 1.073 (1.032–1.116), P < 0.001), separated (HR (95% CI): 1.074 (0.953–1.211), P = 0.240), divorced (HR (95% CI): 1.144 (1.099–1.190), P < 0.001) and widowed (HR (95% CI): 1.100 (1.058–1.144), P < 0.001) (Table 3).
Table 3
Univariate and multivariate analysis of overall survival and cancer specific survival after propensity score matching
|
Univariate
|
multivariate
|
Variable
|
Overall survival
|
Cancer specific survival
|
Overall survival
|
Cancer specific survival
|
|
Hazard ratio(95%CI)
|
P value
|
Hazard ratio(95%CI)
|
P value
|
Hazard ratio(95%CI)
|
P value
|
Hazard ratio(95%CI)
|
P value
|
Gender
|
|
|
|
|
|
|
|
|
Male
|
Reference
|
Reference
|
Reference
|
Reference
|
Female
|
0.618(0.602–0.634)
|
< 0.001
|
0.618(0.602–0.634)
|
< 0.001
|
0.772(0.752–0.793)
|
< 0.001
|
0.791(0.769–0.814)
|
< 0.001
|
Age
|
|
|
|
|
|
|
|
|
≤ 65
|
Reference
|
Reference
|
Reference
|
Reference
|
༞65
|
1.130(1.101–1.160)
|
< 0.001
|
1.130(1.101–1.160)
|
< 0.001
|
1.188(1.156–1.222)
|
< 0.001
|
1.129(1.095–1.163)
|
< 0.001
|
Race
|
|
|
|
|
|
|
|
|
White
|
Reference
|
Reference
|
Reference
|
Reference
|
Black
|
1.152(1.106-1.200)
|
< 0.001
|
1.152(1.106-1.200)
|
< 0.001
|
0.945(0.906–0.985)
|
0.007
|
0.936(0.895–0.978)
|
0.003
|
Other
|
0.836(0.790–0.885)
|
< 0.001
|
0.836(0.790–0.885)
|
< 0.001
|
0.749(0.707–0.794)
|
< 0.001
|
0.781(0.736–0.830)
|
< 0.001
|
Histology
|
|
|
|
|
|
|
|
|
ADC
|
Reference
|
Reference
|
Reference
|
Reference
|
SCC
|
1.480(1.442–1.520)
|
< 0.001
|
1.480(1.442–1.520)
|
< 0.001
|
1.184(1.151–1.218)
|
< 0.001
|
1.137(1.103–1.173)
|
< 0.001
|
LCC
|
1.651(1.504–1.812)
|
< 0.001
|
1.651(1.504–1.812)
|
< 0.001
|
1.381(1.246–1.530)
|
< 0.001
|
1.405(1.262–1.565)
|
< 0.001
|
ASC
|
1.114(1.003–1.236)
|
0.043
|
1.114(1.003–1.236)
|
0.043
|
1.204(1.084–1.337)
|
0.001
|
1.181(1.053–1.324)
|
0.004
|
Marital status
|
|
|
|
|
|
|
|
|
Married
|
Reference
|
Reference
|
Reference
|
Reference
|
Single
|
1.047(1.009–1.087)
|
0.015
|
1.047(1.009–1.087)
|
0.015
|
1.085(1.046–1.126)
|
< 0.001
|
1.073(1.032–1.116)
|
< 0.001
|
Separated
|
1.059(0.949–1.182)
|
0.305
|
1.059(0.949–1.182)
|
0.305
|
1.137(1.019–1.270)
|
0.022
|
1.074(0.953–1.211)
|
0.24
|
Divorced
|
1.125(1.085–1.166)
|
< 0.001
|
1.125(1.085–1.166)
|
< 0.001
|
1.148(1.106–1.192)
|
< 0.001
|
1.144(1.099–1.190)
|
< 0.001
|
Widowed
|
1.093(1.056–1.132)
|
< 0.001
|
1.093(1.056–1.132)
|
< 0.001
|
1.139(1.099–1.181)
|
< 0.001
|
1.100(1.058–1.144)
|
< 0.001
|
Grade
|
|
|
|
|
|
|
|
|
Well differentiated
|
Reference
|
Reference
|
Reference
|
Reference
|
Moderately differentiated
|
1.919(1.815–2.028)
|
< 0.001
|
1.919(1.815–2.028)
|
< 0.001
|
1.382(1.306–1.462)
|
< 0.001
|
1.399(1.313–1.491)
|
< 0.001
|
Poorly differentiated
|
2.981(2.824–3.147)
|
< 0.001
|
2.981(2.824–3.147)
|
< 0.001
|
1.642(1.553–1.737)
|
< 0.001
|
1.690(1.587–1.799)
|
< 0.001
|
Undifferentiated
|
3.073(2.719–3.472)
|
< 0.001
|
3.073(2.719–3.472)
|
< 0.001
|
1.546(1.352–1.768)
|
< 0.001
|
1.597(1.369–1.821)
|
< 0.001
|
Stage
|
|
|
|
|
|
|
|
|
I
|
Reference
|
Reference
|
Reference
|
Reference
|
II
|
2.058(1.975–2.164)
|
< 0.001
|
2.058(1.975–2.164)
|
< 0.001
|
2.230(2.118–2.349)
|
< 0.001
|
2.974(2.772–3.133)
|
< 0.001
|
III
|
3.779(3.627–3.937)
|
< 0.001
|
3.779(3.627–3.937)
|
< 0.001
|
3.181(3.030–3.399)
|
< 0.001
|
4.553(4.302–4.819)
|
< 0.001
|
IV
|
7.952(7.657–8.258)
|
< 0.001
|
7.952(7.657–8.258)
|
< 0.001
|
5.435(5.178–5.704)
|
< 0.001
|
7.974(7.535–8.439)
|
< 0.001
|
Surgery of primary site
|
|
|
|
|
|
|
|
|
No
|
Reference
|
Reference
|
Reference
|
Reference
|
Yes
|
0.185(0.180–0.191)
|
< 0.001
|
0.185(0.180–0.191)
|
< 0.001
|
0.460(0.434–0.487)
|
< 0.001
|
0.442(0.416–0.470)
|
< 0.001
|
Intraoperative lymph node evaluation
|
|
|
|
|
|
|
|
|
No
|
Reference
|
Reference
|
Reference
|
Reference
|
Yes
|
0.223(0.216–0.229)
|
< 0.001
|
0.223(0.216–0.229)
|
< 0.001
|
0.725(0.690–0.763)
|
< 0.001
|
0.735(0.697–0.776)
|
< 0.001
|
Chemotherapy
|
|
|
|
|
|
|
|
|
No
|
Reference
|
Reference
|
Reference
|
Reference
|
Yes
|
1.559(1.520–1.599)
|
< 0.001
|
1.559(1.520–1.599)
|
< 0.001
|
0.555(0.539–0.572)
|
< 0.001
|
0.561(0.544–0.579)
|
< 0.001
|
Radiotherapy
|
|
|
|
|
|
|
|
|
No
|
Reference
|
Reference
|
Reference
|
Reference
|
Yes
|
2.090(2.037–2.144)
|
< 0.001
|
2.090(2.037–2.144)
|
< 0.001
|
0.987(0.950–1.007)
|
0.142
|
0.984(0.955–1.015)
|
0.307
|
ADC Adenocarcinoma, SCC Squamous cell carcinoma, LCC Large Cell Carcinoma, ASC Adenosquamous carcinoma, |
In further subgroup analysis, all subgroups of age, gender, stage, surgery of primary site, intraoperative lymph node evaluation, chemotherapy and radiotherapy, unmarried patients had significantly worse OS compared to married patients. Similarly, we demonstrated that unmarried patients also had significantly worse CSS in the above subgroups compared to married patients, except in the well differentiated and stage II subgroups with higher risks in the OS (Fig. 3).