Patient characteristics
A total of 1641 patients with stage Ⅰa NSCLC were included, including 755 (46%) who received surgery and 886 (54%) radiotherapy. The median age of the entire cohort was 83 years, and the median follow-up was 42 months. Baseline demographics and clinical characteristics for the surgery and radiotherapy groups are described in detail in Table 1. Most patients who underwent surgery received either lobectomy (63.4%) or wedge resection (27.5%). Regional LNE was conducted in 611(80.9%) patients in the surgery cohort. Of the 886 patients who received radiotherapy, reasons of no cancer-directed surgery in 808 (91.2%) were “not recommended”, and only 78 (8.8%) patients “recommended but not performed, patient refused”. Compared with surgery, patients treated with radiotherapy were older, later diagnosed, and had more squamous cell carcinoma, unknown grade and increased tumor size.
Table 1 Baseline demographics and clinical characteristics
|
N (%)
|
P Value
|
Variable
|
Surgery
(N = 755)
|
Radiotherapy
(N = 886)
|
Age, median ± SD, y
|
82.6 ± 2.4
|
84.1 ± 3.1
|
<0.001
|
Sex
|
|
|
0.491
|
Male
|
298(39.5%)
|
335(37.8%)
|
Female
|
457(60.5%)
|
551(62.2%)
|
Race
|
|
|
0.149
|
White
|
652(86.4%)
|
754(85.1%)
|
Black
|
40(5.3%)
|
67(7.6%)
|
Other
|
63(8.3%)
|
65(7.3%)
|
Year of diagnosis
|
|
|
<0.001
|
2012-2014
|
393(52.1%)
|
364(41.1%)
|
|
2015-2017
|
362(47.9%)
|
522(58.9%)
|
|
Tumor size, cm
|
|
|
<0.001
|
T ≤ 1 cm
|
69(9.1%)
|
35(3.9%)
|
|
1 < T ≤ 2 cm
|
373(49.4%)
|
379(42.8%)
|
|
2 < T ≤3 cm
|
313(41.5%)
|
472(52.3%)
|
|
Histology
|
|
|
<0.001
|
Adenocarcinoma
|
520(68.9%)
|
511(57.7%)
|
Squamous cell carcinoma
|
159(21.0%)
|
304(34.3%)
|
Other
|
76(10.1%)
|
71(8.0%)
|
Grade
|
|
|
<0.001
|
Well differentiated
|
201(26.6%)
|
98(11.0%)
|
Moderately differentiated
|
335(44.4%)
|
187(21.1%)
|
Poorly or undifferentiated
|
163(21.6%)
|
169(19.1%)
|
Unknown
|
56(7.4%)
|
432(48.8%)
|
Tumor location
|
|
|
0.023
|
Right upper lobe
|
251(33.3%)
|
300(33.9%)
|
Right middle lobe
|
56(7.4%)
|
32(3.6%)
|
Right lower lobe
|
143(18.9%)
|
164(18.5%)
|
Left upper lobe
|
185(24.5%)
|
235(26.5%)
|
Left lower lobe
|
111(14.7%)
|
139(15.7%)
|
Other
|
9(1.2%)
|
16(1.8%)
|
Survival Analysis
Unadjusted Kaplan–Meier survival curves for the unmatched groups are shown in Fig. 1. The median OS time for the entire cohort was 56.0 months (95% confidence interval [CI], 51.7-60.3 months). The OS (P<0.001) and CSS (P<0.001) of the surgery group was higher than that of the radiotherapy group. The median OS time was not reached in surgery group and 41.0 months (95% CI, 36.7-45.3 months) in radiotherapy group. The 1-, 3-, and 5-year OS rates were 91.4%, 78.6%, and 63.6% for the surgery group, 87.2%, 54.4%, and 30.4% for the radiotherapy group, respectively. The 1-, 3-, and 5-year cancer-specific survival rates were 95.9%, 89.4%, and 81.4% for surgery group, and 92.9%, 74.8%, and 62.6% for radiotherapy group, respectively.
Univariate and multivariate analyses of the predictors for OS are shown in Table 2. The age of diagnosis, sex, years of diagnosis, tumor size, histology, grade, and treatment pattern were significantly associated with survival in univariate analysis. On multivariate Cox regression analysis, patients who underwent radiotherapy had significantly worse survival as compared with patients who had surgery (hazard ratio 2.426; 95% CI, 2.003 to 2.939; P<.001). Younger age, female sex, later year of diagnosis, adenocarcinoma histology, well or moderately differentiation, and smaller tumor size were independent prognostic factors for better OS.
Table 2 Cox regression analyses of overall survival in patients treated with surgery or radiotherapy
Variable
|
Univariate
|
Multivariate
|
HR(95%CI)
|
P value
|
HR(95%CI)
|
P value
|
Age, y
|
1.070(1.042-1.098)
|
<.001
|
1.029(1.001-1.058)
|
0.045
|
Sex
|
|
|
|
|
Male
|
1.000 (Ref)
|
|
1.000 (Ref)
|
|
Female
|
0.692(0.592-0.809)
|
<.001
|
0.712(0.608-0.835)
|
<.001
|
Race
|
|
|
|
|
White
|
1.000 (Ref)
|
|
|
|
Black
|
1.184(0.879-1.595)
|
0.266
|
|
|
Others
|
0.751(0.543-1.039)
|
0.084
|
|
|
Year of diagnosis
|
|
|
|
|
2012-2014
|
1.000 (Ref)
|
|
1.000 (Ref)
|
|
2015-2017
|
0.798(0.669-0.952)
|
0.012
|
0.747(0.625-0.892)
|
0.001
|
Tumor size, cm
|
|
|
|
|
T ≤ 1 cm
|
1.000 (Ref)
|
|
1.000 (Ref)
|
|
1 < T ≤ 2 cm
|
1.733(1.123-2.676)
|
0.013
|
1.358(0.877-2.102)
|
0.170
|
2 < T ≤3 cm
|
2.307(1.499-3.550)
|
<.001
|
1.615(1.043-2.500)
|
0.032
|
Histology
|
|
|
|
|
Adenocarcinoma
|
1.000 (Ref)
|
|
1.000 (Ref)
|
|
Squamous cell carcinoma
|
1.714(1.452-2.024)
|
<.001
|
1.342(1.121-1.607)
|
0.001
|
Others
|
1.123(0.854-1.477)
|
0.405
|
1.037(0.782-1.376)
|
0.799
|
Grade
|
|
|
|
|
Well differentiated
|
1.000 (Ref)
|
|
1.000 (Ref)
|
|
Moderately differentiated
|
1.496(1.159-1.931)
|
0.002
|
1.268(0.974-1.652)
|
0.078
|
Poorly or undifferentiated
|
2.136(1.641-2.779)
|
<.001
|
1.457(1.094-1.940)
|
0.010
|
Unknown
|
1.966(1.525-2.534)
|
<.001
|
1.055(0.083-1.387)
|
0.699
|
Tumor location
|
|
|
|
|
Left upper lobe
|
1.000 (Ref)
|
|
|
|
Left lower lobe
|
1.075(0.838-1.378)
|
0.569
|
|
|
Right upper lobe
|
0.988(0.805-1.212)
|
0.905
|
|
|
Right middle lobe
|
0.777(0.514-1.177)
|
0.234
|
|
|
Right lower lobe
|
1.087(0.862-1.372)
|
0.480
|
|
|
Other
|
1.394(0.775-2.507)
|
0.267
|
|
|
Treatment
|
|
|
|
|
Operation
|
1.000 (Ref)
|
|
1.000 (Ref)
|
|
Radiotherapy
|
2.449(2.073-2.893)
|
<.001
|
2.426(2.003-2.939)
|
<.001
|
Propensity score matching(PSM) based on age, sex, race, year of diagnosis, tumor size, histology, and pathologic grade resulted in 372 patients in both surgery and radiotherapy groups (1:1 ratio). The demographics and clinical variables were well balanced as shown in Tables 3. After PSM, the OS (P<0.001) and CSS (P<0.001) of the surgery group were still higher than that of the radiotherapy group. Median survival time were 79.0 and 41.0 months in the surgery and radiotherapy groups, respectively. The 1-, 3-, and 5-year OS rates were 90.0%, 76.9%, and 59.9% in the surgery group, and 86.0%, 54.3%, and 28.0% in the radiotherapy group. The 1-, 3-, and 5-year cancer-specific survival rates were 94.5%, 86.1%, and 78.0% in surgery group, and 90.7%, 74.5%, and 61.0% in radiotherapy group. (Fig. 2).
Table 3 Characteristics of patients in the surgery and radiotherapy groups after propensity score matching
Variable
|
N (%)
|
P Value
|
Surgery
(N = 372)
|
Radiotherapy
(N = 372)
|
Age, median ± SD, y
|
83.2 ± 2.5
|
83.0 ± 2.6
|
0.208
|
Sex
|
|
|
0.881
|
Male
|
150(40.3%)
|
148(39.8%)
|
Female
|
222(59.7%)
|
224(60.2%)
|
Race
|
|
|
0.514
|
White
|
327(87.9%)
|
321(86.3%)
|
Black
|
16(4.3%)
|
23(6.2%)
|
Other
|
29(7.8%)
|
28(7.5%)
|
Year of diagnosis
|
|
|
0.825
|
2012-2014
|
174(46.8%)
|
171(46.0%)
|
2015-2017
|
198(53.2%)
|
201(54.0%)
|
Tumor size, cm
|
|
|
0.404
|
T ≤ 1 cm
|
25(6.7%)
|
17(4.6%)
|
1 < T ≤ 2 cm
|
168(45.2%)
|
178(47.8%)
|
2 < T ≤3 cm
|
179(48.1%)
|
177(47.6%)
|
Histology
|
|
|
0.205
|
Adenocarcinoma
|
245(65.9%)
|
244(65.6%)
|
Squamous cell carcinoma
|
97(26.1%)
|
109(29.3%)
|
Other
|
30(8.1%)
|
19(5.1%)
|
Grade
|
|
|
0.297
|
Well differentiated
|
66(17.7%)
|
73(19.6%)
|
Moderately differentiated
|
158(42.5%)
|
146(39.2%)
|
Poorly or undifferentiated
|
98(26.3%)
|
87(23.4%)
|
Unknown
|
50(13.4%)
|
66(17.7%)
|
Survival was also compared in matched subgroups of surgery without LNE versus radiotherapy. The demographics and clinical variables were well matched after propensity matching (Online Resource 1). Kaplan–Meier survival curves for the matched groups are displayed in Fig.3. No differences in the OS (P =0.146) and CSS (P =0.675) were found between the surgery without LNE and radiotherapy group.