Study selection and quality
A total of 10 studies25-34 including 1119 patients (361 patients in the surgery group and 758 patients in the no surgery group) met the eligibility criteria and were included in the final analysis (Figure 1). Manual searches of the references lists of the included studies did not yield any further studies. The quality of the included studies ranged from 3 to 7 on the NOS. The detailed quality assessment and scores for each study are provided in supplementary material Table S1.
Patient characteristics
The main features and demographic data of the studies included are shown in Table 1. Among these 10 studies, 7 studies were aimed at patient response to IM treatment, and the other 3 studies contained a small number of patients with progressive disease (PD). A total of 1089 patients (97.32%) with good response (complete response or partial response) or stable disease and 30 patients (2.68%) with PD were included in analysis, with an R0 resection rate ranging from 41.1% to 100%.
Table 1. Summary of studies included
Study
|
Year
|
Design
|
Sample (n)
|
Extension of
diseasea
|
Response to
first-line Imatinib (n, CR/PR/SD/PD)
|
R0 resection rate (%)
|
Follow-upb (months)
|
NOS
|
S
|
NS
|
S
|
NS
|
Bauer et al.
|
2005
|
R
|
12
|
66
|
1
|
8/42/18/0
|
91.7
|
29.8
|
25.7
|
5
|
Blesius et al.
|
2011
|
P
|
9
|
16
|
3
|
0/15/7/3
|
62.5
|
53.5
|
53.5
|
4
|
Chang et al.
|
2015
|
R
|
76
|
106
|
1, 2
|
20/110/29/23
|
41.1
|
66.5
|
71.0
|
6
|
Du et al.
|
2014
|
RCT
|
19
|
22
|
1, 2
|
0/24/17/0
|
73.7
|
23
|
49
|
RCT
|
Kim et al.
|
2019
|
R
|
109
|
203
|
1, 2
|
24/185/103/0
|
NA
|
73.2
|
73.2
|
4
|
Park et al.
|
2014
|
R
|
42
|
92
|
1, 2
|
5/90/39/0
|
62.0
|
58.9
|
58.9
|
7
|
Rubió et al.
|
2015
|
R
|
27
|
144
|
1, 2, 3
|
NAc
|
70.4
|
56.6
|
56.6
|
4
|
Shen et al.
|
2015
|
R
|
10
|
15
|
1, 3
|
0/25/0
|
100.0
|
21.5
|
21.5
|
3
|
Wang et al.
|
2020
|
R
|
36
|
15
|
1, 2, 3
|
0/24/23/4
|
84.4
|
43.7
|
43.7
|
6
|
Xiao et al.
|
2018
|
R
|
21
|
79
|
1
|
4/48/48/0
|
71.4
|
63.5
|
53.5
|
6
|
Abbreviations: R, Retrospective study; P, Prospective cohort study; RCT, Randomized controlled trail; S, Surgery group; NS, No surgery group; CR, Complete response; PR, Partial response; SD, Stable disease; PD, Progressive disease; NOS, Newcastle-Ottawa Scale; NA, data not available.
Notes: aExtension of disease: 1 = Metastasis, 2 = Local recurrence, 3 = Locally advanced initially unresectable.
bMean or median.
cThis study focused on patients response to IM treatment without patient with progressive disease. However, detailed information is not available.
As shown in Table 2, patient clinical characteristics were compared between the surgery group and the no surgery group. Patients in the surgery group were significantly younger than patients in the no surgery group (WMD, -5.02, 95% CI, -8.38 to -1.67, P = 0.003). There were no significant differences observed regarding gender, tumor size, primary and metastatic tumor site, genotype of primary tumor, or response to first-line imatinib between the two groups.
Table 2. Results of meta-analysis comparing clinical characteristics
Characteristics
|
Studies (n)
|
No. of patients (n)
|
WMD/ORa
(95% CI)
|
p value
|
Study heterogeneity
|
S
|
NS
|
|
|
I2 (%)
|
p value
|
Gender (male/female)
|
9
|
149/103
|
366/203
|
0.71
(0.51, 1.01)
|
0.060
|
0
|
0.55
|
Ageb (years)
|
7
|
54.44
|
59.45
|
-5.02
(-8.38, -1.67)
|
0.003
|
75
|
0.0005
|
Primary tumor sizeb (cm)
|
3
|
5.47
|
4.85
|
-0.31
(-0.84, 0.21)
|
0.240
|
0
|
0.93
|
Primary tumor site (gastric/non-gastric)
|
9
|
78/174
|
217/352
|
0.73
(0.52, 1.02)
|
0.060
|
0
|
0.89
|
Genotype of primary tumor
(KIT exon 11 mutation/Others)
|
4
|
44/26
|
131/60
|
1.51
(0.81, 2.84)
|
0.200
|
16
|
0.31
|
Sites of metastasis (liver/Others)
|
4
|
92/59
|
270/150
|
0.78
(0.19, 3.12)
|
0.720
|
86
|
0.0007
|
Response to first-line imatinib
(CR+PR/SD+PD)
|
7
|
136/36
|
255/103
|
1.26
(0.49, 3.24)
|
0.630
|
77
|
0.0007
|
Response to first-line imatinib
(CR+PR/SD)
|
5c
|
65/39
|
181/93
|
0.72
(0.31, 1.68)
|
0.450
|
52
|
0.10
|
Abbreviations: S, Surgery group; NS, No surgery group; WMD, Weighted mean difference; OR, Odds ratio; CI, Confidence interval; CR, Complete response; PR, Partial response; SD, Stable disease; PD, Progressive disease.
Notes: aOdds ratio.
bMean age/tumor size.
cIncluding studies involved in subgroup analysis.
Oncologic outcomes
In the overall population, pooled data showed a significant improvement in OS (HR, 0.62; 95% CI, 0.53 to 0.73; P < 0.0001; Figure 2A) and PFS (HR, 0.57; 95% CI, 0.44 to 0.72; P < 0.0001; Figure 2B) after surgery compared with IM treatment alone.
Subgroup analysis
Subgroup analyses were performed to further investigate the impact of surgery on patients who respond to IM treatment. Studies that contain patients with PD were excluded. A total of 7 studies25,28-32,34 including 863 patients (240 patients in the surgery group and 621 patients in the no surgery group) were included in the subgroup analyses. Subgroup analysis results were consistent with the overall results (OS: HR, 0.67; 95% CI, 0.55 to 0.81; P < 0.0001; Figure 3A; PFS: HR, 0.62; 95% CI, 0.46 to 0.82; P = 0.009; Figure 3B).
Sensitivity analysis and publication bias
One randomized control trial28 and 4 retrospective studies27,30,33,34 with scores of six or higher on the NOS were included in the sensitivity analysis. The results related to OS and PFS did not changed significantly in the sensitivity analysis (shown in supplementary material Figure S1 and Figure S2).
As shown in Figure 4, a funnel plot was constructed for the studies included in this meta-analysis that reported OS. All studies lie inside the 95% CIs, with an even distribution around the vertical axis, indicating no obvious publication bias.