Demographic characteristics before and after PSM
In total, 476,757 NSCLC patients were identified from 2004 to 2016 in the SEER database, of which, 24,268 stage IV NSCLC patients met the inclusion criteria, the screening process is shown in Fig. 1. Of all eligible patients, 4,114 (16.95%) underwent surgical treatment to primary tumor site, 2,045 (49.71%) of these patients underwent lobectomy and 1,766 (42.93%) received sub-lobar resection, others underwent pneumonectomy and biopsy, which were not included in this analysis. Obvious differences in age, histology, differentiation, tumor position, TNM stage, radiation chemotherapy and distant surgery were noted between the lobectomy and sub-lobar resection groups. (Table 1) This indicated that the baseline characteristics of the two groups were not balanced. Specifically, lobectomy group was associated with lower T stage patients. After the 1:1 PSM, 1,288 stage IV NSCLC patients treated with lobectomy (n = 644) or sub-lobar resection (n = 644) were enrolled in the survival analysis. Baseline characteristics were all well balanced (Table 1).
Table 1
Demographic Information for Patients with Stage IV NSCLC before and after PSM
| Before PSM | | After PSM | |
| Sub-lobectomy | Lobectomy | SMD | Sub-lobectomy | Lobectomy | SMD |
| (n = 1766) | (n = 2045) | (n = 644) | (n = 644) |
Age | | | | | | |
< 60 | 540 (30.6) | 685 (33.5) | 0.566 | 201 (31.2) | 184 (28.6) | < 0.001 |
60–75 | 879 (49.8) | 1062 (51.9) | 326 (50.6) | 342 (53.1) |
> 75 | 347 (19.6) | 298 (14.6) | 117 (18.2) | 118 (18.3) |
Gender | | | | | | |
Male | 862 (48.8) | 1008 (49.3) | < 0.001 | 322 (50.0) | 309 (48.0) | < 0.001 |
Female | 904 (51.2) | 1037 (50.7) | 322 (50.0) | 335 (52.0) |
Histology | | | | | | |
Squamous cell carcinoma | 205 (11.6) | 336 (16.4) | 0.016 | 83 (12.9) | 89 (13.8) | < 0.001 |
Adenocarcinoma | 1330 (75.3) | 1312 (64.2) | 468 (72.7) | 445 (69.1) |
Other | 231 (13.1) | 397 (19.4) | 93 (14.4) | 110 (17.1) |
Differentiation | | | | | | |
Well | 195 (11.1) | 162 (7.9) | 0.023 | 59 (9.2) | 69 (10.7) | < 0.001 |
Moderately differentiated | 541 (30.6) | 628 (30.6) | 194 (30.1) | 182 (28.3) |
Poory differentiated | 595 (33.7) | 905 (44.3) | 248 (38.5) | 246 (38.2) |
undifferentiated | 55 (3.1) | 81 (4.0) | 23 (3.6) | 26 (4.0) |
Unknown | 380 (21.5) | 269 (13.2) | 120 (18.6) | 121 (18.8) |
Position | | | | | | |
Bronchus | 13 (0.7) | 10 (0.5) | 0.057 | 4 (0.6) | 2 (0.3) | < 0.001 |
Lobe | 1450 (82.1) | 1883 (92.1) | 557 (86.5) | 558 (86.6) |
Overlapping lesion | 35 (2.0) | 52 (2.5) | 11 (1.7) | 16 (2.5) |
Unknown | 268 (15.2) | 100 (4.9) | 72 (11.2) | 68 (10.6) |
AJCC T status | | | | | | |
T1 | 304 (17.2) | 381 (18.6) | 0.497 | 138 (21.4) | 158 (24.5) | < 0.001 |
T2 | 375 (21.3) | 872 (42.7) | 195 (30.3) | 195 (30.3) |
T3 | 308 (17.4) | 350 (17.1) | 107 (16.6) | 107 (16.6) |
T4 | 779 (44.1) | 442 (21.6) | 204 (31.7) | 184 (28.6) |
AJCC N status | | | | | | |
N0 | 947 (53.6) | 1070 (52.3) | 0.148 | 340 (52.8) | 364 (56.5) | 0.023 |
N1 | 145 (8.2) | 382 (18.7) | 64 (9.9) | 77 (12.0) |
N2 | 537 (30.4) | 542 (26.5) | 205 (31.9) | 170 (26.4) |
N3 | 137 (7.8) | 51 (2.5) | 35 (5.4) | 33 (5.1) |
AJCC M status | | | | | | |
M1a | 475 (26.9) | 373 (18.3) | 0.856 | 141 (21.9) | 149 (23.1) | < 0.001 |
M1b | 390 (22.1) | 575 (28.1) | 148 (23.0) | 148 (23.0) |
M1 | 901 (51.0) | 1097 (53.6) | 355 (55.1) | 347 (53.9) |
LN dissection | | | | | | |
No | 1243 (70.5) | 231 (57.8) | 0.308 | 194 (30.1) | 211 (32.8) | 0.041 |
Yes | 523 (29.5) | 1814 (88.7) | 450 (69.9) | 433 (67.2) |
Radiation | | | | | | |
No | 1245 (70.5) | 1181 (57.8) | 0.953 | 423 (65.7) | 422 (65.5) | 0.002 |
Yes | 521 (29.5) | 864 (42.2) | 221 (34.3) | 222 (34.5) |
Chemotherapy | | | | | | |
No/Unknown | 722 (40.9) | 892 (43.6) | 0.261 | 270 (41.9) | 290 (45.0) | < 0.001 |
Yes | 1044 (59.1) | 1153 (56.4) | 374 (58.1) | 354 (55.0) |
Surgery to metastasis site | | | | | | |
No | 1021 (57.8) | 1374 (67.2) | 0.118 | 313 (48.6) | 359 (55.7) | 0.033 |
Yes | 745 (42.2) | 671 (32.8) | | 331 (51.4) | 285 (44.3) | |
PSM, propensity score matching; NSCLC, non-small cell lung cancer; LN, lymph node; AJCC, American Joint Committee on Cancer |
Logistic analysis was performed to evaluated which variables were associated with lobectomy (Table 2). Compared with patients under 60 years old, patients over 75 years old tend to receive more sub-lobar resection than lobectomy (HR = 0.71, 95% CI 0.55–0.91, P = 0.007). In addition, T4 patients received less lobectomy compared with T1 or T2 patients. Patients who received radiation therapy also receive more lobectomy than patients with no radiotherapy (HR = 1.30, 95% CI 1.08–1.56, P = 0.005).
Table 2
Logistic Regression Model for stage IV NSCLC patients underwent lobectomy or sub-lobar resection
| Univariate Analysis | | Multivariate Analysis | |
| Odds Ratios | | Odds Ratios | |
Characteristic | (95%CI) | P Value | (95%CI) | P Value |
Age | | | | |
< 60 | 1.00 (reference) | | 1.00 (reference) | |
60–75 | 0.94 (0.78–1.34) | 0.531 | 0.94 (0.78–1.14) | 0.551 |
> 75 | 0.70 (0.54–0.90) | 0.006 | 0.71 (0.55–0.91) | 0.007 |
Gender | | | | |
Male | 1.00 (reference) | | / | / |
Female | 1.02 (0.86–1.20) | 0.859 | / | / |
Histology | | | | |
Squamous cell carcinoma | 1.00 (reference) | | 1.00 (reference) | |
Adenocarcinoma | 0.66 (0.52–0.85) | 0.001 | 0.67 (0.52–0.85) | 0.001 |
Other | 1.06 (0.77–1.45) | 0.732 | 1.05 (0.78–1.43) | 0.742 |
Differentiation | | | | |
Well | 1.00 (reference) | | / | / |
Moderately differentiated | 0.96 (0.71–1.31) | 0.805 | / | / |
Poory differentiated | 0.98 (0.72–1.33) | 0.884 | / | / |
Undifferentiated | 0.84 (0.49–1.45) | 0.535 | / | / |
Unknown | 1.06 (0.75–1.50) | 0.731 | / | / |
Position | | | | |
Bronchus | 1.00 (reference) | | 1.00 (reference) | |
Lobe | 1.44 (0.49–4.27) | 0.509 | 1.42 (0.48–4.20) | 0.526 |
Overlapping lesion | 1.80 (0.53–6.05) | 0.344 | 1.77 (0.53–5.97) | 0.356 |
Unknown | 0.75 (0.25–2.30) | 0.616 | 0.75 (0.24–2.30) | 0.749 |
AJCC T status | | | | |
T1 | 1.00 (reference) | | 1.00 (reference) | |
T2 | 1.62 (1.28–2.06) | < 0.001 | 1.61 (1.27–2.04) | < 0.001 |
T3 | 1.18 (0.89–1.56) | 0.244 | 1.17 (0.89–1.55) | 0.257 |
T4 | 0.76 (0.60–0.97) | 0.029 | 0.76 (0.60–0.97) | 0.025 |
AJCC N status | | | | |
N0 | 1.00 (reference) | | 1.00 (reference) | |
N1 | 1.46 (1.23–1.90) | 0.004 | 1.45 (1.12–1.88) | 0.005 |
N2 | 0.81 (0.66–0.98) | 0.029 | 0.80 (0.66–0.97) | 0.02 |
N3 | 0.55 (0.37–0.84) | 0.005 | 0.55 (0.36–0.83) | 0.005 |
AJCC M status | | | | |
M1a | 1.00 (reference) | | 1.00 (reference) | |
M1b | 1.25 (0.97–1.61) | 0.088 | 1.24 (0.96–1.60) | 0.002 |
M1 | 1.04 (0.84–1.30) | 0.705 | 1.04 (0.84–1.29) | 0.723 |
Lymph-nodes dissection | | | | |
No | 1.00 (reference) | | 1.00 (reference) | |
Yes | 15.47 (12.91–18.54) | < 0.001 | 15.32 (12.82–18.30) | < 0.001 |
Radiation | | | | |
No | 1.00 (reference) | | 1.00 (reference) | |
Yes | 1.31 (1.09–1.58) | 0.005 | 1.30 (1.08–1.56) | 0.005 |
Chemotherapy | | | | |
No | 1.00 (reference) | | / | / |
Yes | 0.95 (0.79–1.13) | 0.537 | / | / |
NSCLC, non-small cell lung cancer; AJCC, American Joint Committee on Cancer |
Impact of surgery types on survival outcomes in IV NSCLC patients
Kaplan-Meier analyses and log-rank test were used in the matched population, patients who underwent lobectomy enjoyed longer CSS and OS compared with sub-lobar resection. The median CSS time was 29 months for patients who underwent lobectomy and 18 months for patients who received sub-lobar resection after PSM (HR = 0.70, 95% CI 0.61–0.80, P < 0.001) (Fig. 2A). The median OS was 25 and 16 months in lobectomy group and sub-lobar resection group (HR = 0.73, 95% CI 0.65–0.83, P < 0.001) (Fig. 2B), respectively. The 1, 2 and 3-year survival rate after PSM also favored the lobectomy group. (Table 3)
Table 3
Survival rate of stage IV NSCLC patients according to different types of surgery
| Cancer Specific Survival | | Overall Survival | |
| Sub-lobectomy VS. Lobectomy | P value | Sub-lobectomy VS. Lobectomy | P value |
1-year survival rate | 59.0% vs. 72.7% | < 0.001 | 56.7% vs. 70.3% | < 0.001 |
2-year survival rate | 43.2% vs. 54.9% | < 0.001 | 40.9% vs. 51.5% | < 0.001 |
3-year survival rate | 31.9% vs. 44.8% | 0.001 | 29.1% vs. 41.0% | 0.001 |
NSCLC, non-small cell lung cancer |
Primary tumor lobectomy as an independent prognostic factor for survival in IV NSCLC patients
In multivariate Cox analysis (Table 4) of the matched population, lobectomy persisted to be independently associated with better CSS (HR = 0.67, 95% CI 0.58–0.77, P < 0.001) and OS (HR = 0.69, 95% CI 0.61–0.79, P < 0.001). Age, gender, TNM stage, histology, differentiation, lymph node dissections, chemotherapy, radiotherapy were all independent factors for survival of stage IV NSCLC patients.
Table 4
Cox Proportional Hazards Regression Model for Lung Cancer–Specific Survival in Patients with NSCLC with surgery
| | Cancer Specific Survival | | | | Overall Survival | | |
| Univariate Analysis | Multivariate Analysis | | Univariate Analysis | Multivariate Analysis |
Characteristic | HR (95%CI) | P | (95%CI) | P | | HR (95%CI) | P | (95%CI) | P |
| Value | Value | | Value | Value |
Age | | | | | | | | | |
< 60 | 1.00 (reference) | | 1.00 (reference) | | | 1.00 (reference) | | 1.00 (reference) | |
60–75 | 1.13 (0.97–1.32) | 0.112 | 1.22 (1.04–1.43) | 0.017 | | 1.16 (1.00-1.35) | 0.045 | 1.24 (1.06–1.44) | 0.007 |
> 75 | 1.27 (1.04–1.55) | 0.02 | 1.53 (1.24–1.90) | < 0.001 | | 1.38 (1.14–1.66) | 0.001 | 1.63 (1.33–1.99) | < 0.001 |
Gender | | | | | | | | | |
Male | 1.00 (reference) | | 1.00 (reference) | | | 1.00 (reference) | | 1.00 (reference) | |
Female | 0.67 (0.59–0.77) | < 0.001 | 0.72 (0.62–0.82) | < 0.001 | | 0.66 (0.58–0.75) | < 0.001 | 0.71 (0.62–0.81) | < 0.001 |
Histology | | | | | | | | | |
Squamous cell carcinoma | 1.00 (reference) | | 1.00 (reference) | | | 1.00 (reference) | | 1.00 (reference) | |
Adenocarcinoma | 0.72 (0.59–0.87) | 0.001 | 0.80 (0.65–0.98) | 0.03 | | 0.67 (0.56–0.80) | < 0.001 | 0.75 (0.62–0.91) | 0.004 |
Other | 0.93 (0.73–1.18) | 0.54 | 0.86 (0.67–1.11) | 0.245 | | 0.92 (0.73–1.15) | 0.444 | 0.86 (0.68–1.09) | 0.223 |
Differentiation | | | | | | | | | |
Well | 1.00 (reference) | | 1.00 (reference) | | | 1.00 (reference) | | 1.00 (reference) | |
Moderately differentiated | 1.42 (1.09–1.84) | 0.01 | 1.29 (0.99–1.70) | 0.061 | | 1.34 (1.05–1.71) | 0.018 | 1.24 (0.97–1.59) | 0.09 |
Poory differentiated | 1.87 (1.45–2.41) | < 0.001 | 1.49 (1.14–1.95) | 0.003 | | 1.81 (1.43–2.29) | < 0.001 | 1.45 (1.13–1.85) | 0.003 |
Undifferentiated | 2.49 (1.67–3.70) | < 0.001 | 2.12 (1.39–3.24) | < 0.001 | | 2.47 (1.71–3.57) | < 0.001 | 2.10 (1.42–3.11) | < 0.001 |
Unknown | 1.73 (1.31–2.28) | < 0.001 | 1.41 (1.06–1.88) | 0.018 | | 1.60 (1.24–2.08) | < 0.001 | 1.31 (1.00-1.71) | 0.047 |
Position | | | | | | | | | |
Bronchus | 1.00 (reference) | | / | / | | 1.00 (reference) | | / | / |
Lobe | 1.61 (0.52–5.02) | 0.409 | / | / | | 1.39 (0.52–3.72) | 0.51 | / | / |
Overlapping lesion | 2.78 (0.83–9.29) | 0.097 | / | / | | 2.36 (0.82–6.80) | 0.113 | / | / |
Unknown | 1.54 (0.49–4.86) | 0.462 | / | / | | 1.28 (0.47–3.47) | 0.631 | / | / |
AJCC T status | | | | | | | | | |
T1 | 1.00 (reference) | | 1.00 (reference) | | | 1.00 (reference) | | 1.00 (reference) | |
T2 | 1.46 (1.21–1.77) | < 0.001 | 1.42 (1.17–1.72) | < 0.001 | | 1.38 (1.16–1.65) | < 0.001 | 1.35 (1.13–1.62) | 0.001 |
T3 | 1.47 (1.18–1.84) | 0.001 | 1.52 (1.20–1.92) | < 0.001 | | 1.40 (1.14–1.72) | 0.001 | 1.45 (1.17–1.81) | 0.001 |
T4 | 1.59 (1.32–1.93) | < 0.001 | 1.49 (1.22–1.82) | < 0.001 | | 1.48 (1.24–1.77) | < 0.001 | 1.44 (1.19–1.73) | < 0.001 |
AJCC N status | | | | | | | | | |
N0 | 1.00 (reference) | | 1.00 (reference) | | | 1.00 (reference) | | 1.00 (reference) | |
N1 | 1.64 (1.32–2.02) | < 0.001 | 1.78 (1.43–2.21) | < 0.001 | | 1.48 (1.21–1.82) | < 0.001 | 1.66 (1.35–2.06) | < 0.001 |
N2 | 1.83 (1.58–2.13) | < 0.001 | 1.83 (1.55–2.15) | < 0.001 | | 1.72 (1.49–1.99) | < 0.001 | 1.76 (1.51–2.06) | < 0.001 |
N3 | 1.98 (1.48–2.65) | < 0.001 | 2.04 (1.50–2.76) | < 0.001 | | 1.91 (1.45–2.52) | < 0.001 | 2.02 (1.51–2.70) | < 0.001 |
AJCC M status | | | | | | | | | |
M1a | 1.00 (reference) | | 1.00 (reference) | | | 1.00 (reference) | | 1.00 (reference) | |
M1b | 1.50 (1.20–1.87) | < 0.001 | 1.44 (1.14–1.81) | 0.002 | | 1.49 (1.21–1.85) | < 0.001 | 1.47 (1.18–1.83) | 0.001 |
M1 | 1.45 (1.20–1.74) | < 0.001 | 1.43 (1.18–1.74) | < 0.001 | | 1.44 (1.21–1.72) | < 0.001 | 1.44 (1.20–1.74) | < 0.001 |
Primary surgery | | | | | | | | | |
Sub-lobectomy | 1.00 (reference) | | 1.00 (reference) | | | 1.00 (reference) | | 1.00 (reference) | |
Lobectomy | 0.70 (0.61–0.80) | < 0.001 | 0.67 (0.58–0.77) | < 0.001 | | 0.73 (0.65–0.83) | < 0.001 | 0.69 (0.61–0.79) | < 0.001 |
Lymph nodes dissection | | | | | | | | | |
No | 1.00 (reference) | | 1.00 (reference) | | | 1.00 (reference) | | 1.00 (reference) | |
Yes | 0.79 (0.69–0.91) | 0.001 | 0.76 (0.66–0.88) | < 0.001 | | 0.78 (0.68–0.89) | < 0.001 | 0.74 (0.65–0.86) | < 0.001 |
Radiation | | | | | | | | | |
No | 1.00 (reference) | | 1.00 (reference) | | | 1.00 (reference) | | 1.00 (reference) | |
Yes | 1.39 (1.21–1.60) | < 0.001 | 1.33 (1.14–1.55) | < 0.001 | | 1.36 (1.19–1.55) | < 0.001 | 1.31 (1.13–1.52) | < 0.001 |
Chemotherapy | | | | | | | | | |
No | 1.00 (reference) | | 1.00 (reference) | | | 1.00 (reference) | | 1.00 (reference) | |
Yes | 0.97 (0.85–1.11) | 0.644 | 0.74 (0.64–0.87) | < 0.001 | | 0.90 (0.80–1.03) | 0.114 | 0.71 (0.62–0.83) | < 0.001 |
PSM, propensity score matching; NSCLC, non-small cell lung cancer; LN, lymph node; AJCC, American Joint Committee on Cancer |
Impact of sub-lobar resection on survival outcomes in IV NSCLC patients
We divided sub-lobar resection population into wedge resection and segmentectomy groups, the PSM analysis was conducted to balance the demographic information, which was shown in Supplementary materials. Kaplan-Meier analyses and log-rank test were used in the matched population, patients who underwent wedge resection had similar CSS and OS compared with segmentectomy. The median CSS time was 16 months for patients who underwent wedge resection and 17 months for patients who received segmentectomy after PSM (HR = 0.96, 95% CI 0.70–1.31, P = 0.490) (Fig. 2C). The median OS was 14 and 16 months in wedge resection group and segmentectomy group (HR = 0.96, 95% CI 0.71–1.30, P = 0.390) (Fig. 2D), respectively. The 1, 2 and 3-year survival rate after PSM also showed no difference between the sub-lobar group. (Table 5)
Table 5
Survival rate of stage IV NSCLC patients in the Sublobar Resection cohort
| Cancer Specific Survival | | Overall Survival | |
| Wedge resection VS. Segmentectomy | P value | Wedge resection VS. Segmentectomy | P value |
1-year survival rate | 54.7% vs. 61.7% | 0.103 | 51.6% vs. 61.0% | 0.103 |
2-year survival rate | 42.7% vs. 41.7% | 0.779 | 40.3% vs. 40.4% | 0.792 |
3-year survival rate | 32.1% vs. 32.2% | 0.876 | 29.3% vs. 30.1% | 0.876 |
NSCLC, non-small cell lung cancer |
Impact of lymph node dissection on survival outcomes in IV NSCLC patients
We explore whether lymph node dissection would provide a further survival benefit for stage IV NSCLC patients. According to the multivariate Cox analysis (Table 4) of the matched population, lymph node dissection was independently associated with better CSS (HR = 0.76, 95% CI 0.66–0.88, P < 0.001) and OS (HR = 0.74, 95% CI 0.65–0.86, P < 0.001). We confirmed this result in different types of surgery and found lymph node dissection group persist to have better survival outcomes both in lobectomy group and sub-lobar resection population. (Fig. 3A-D) We further divided all patients into two groups according to lymph node dissection number (< 9 or > = 9). (Fig. 4A-D) The results showed over 9 lymph node dissection only improved survival in sub-lobar resection population (CSS HR = 0.66, 95% CI 0.50–0.87, P = 0.011), but not in lobectomy patients (CSS HR = 0.97, 95% CI 0.70–1.35, P = 0.89).
Subgroup analysis
We further explored whether lobectomy was associated with better survival outcomes in different subtypes of populations. Both CSS (Fig. 5A) and OS (Fig. 5B) outcomes showed similar results. Except for stage T4 and brain metastasis patients, all subtype of NSCLC patients would benefit more from lobectomy than sub-lobar resection.