Stereotactic body radiotherapy versus surgery for early-stage non-small cell lung cancer: an updated meta-analysis involving 29,511 patients included in comparative studies

Viani, Gustavo Arruda; Gouveia, André Guimarães; Yan, Michael; Matsuura, Fernando Konjo; Moraes, Fabio Ynoe

doi:10.36416/1806-3756/e20210390

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Jornal Brasileiro de Pneumologia

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META-ANALYSIS • J. bras. pneumol. 48 (03) • 2022 • https://doi.org/10.36416/1806-3756/e20210390 copy

Stereotactic body radiotherapy versus surgery for early-stage non-small cell lung cancer: an updated meta-analysis involving 29,511 patients included in comparative studies

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Objective:

To evaluate the efficacy of stereotactic body radiotherapy (SBRT) versus surgery for early-stage non-small cell lung cancer (NSCLC) by means of a meta-analysis of comparative studies.

Methods:

Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology guidelines, searches were performed on PubMed, MEDLINE, Embase, and Cochrane Library for eligible studies. The meta-analysis compared the hazard ratios (HR) for overall survival (OS), cancer-specific survival (CSS), and local control (LC). Subgroup and meta-regression analyses evaluated the association of extent of surgical resection, study publication year, tumor staging, propensity score matching, proportion of chemotherapy use, and proportion of pathological lymph node involvement with CSS and OS.

Results:

Thirty studies involving 29,511 patients were included (surgery group: 17,146 patients and SBRT group: 12,365 patients). There was a significant difference in favor of surgery vs. SBRT in the 3-year OS (HR = 1.35; 95% CI: 1.22-1.44; I² = 66%) and 3-year CSS (HR = 1.23; 95% CI: 1.09-1.37; I² = 17%), but not in the 3-year LC (HR = 0.97; 95% CI: 0.93-1.08; I² = 19%). In the subgroup analysis for OS, no significant difference between surgery and SBRT groups was observed in the T1N0M0 subgroup (HR = 1.26; 95% CI: 0.95-1.68; I² = 0%). In subgroup analysis for CSS, no significant difference was detected between the sublobar resection subgroup and the SBRT group (HR = 1.21; 95% CI: 0.96-1.53; I² = 16%).

Conclusions:

Surgery generally resulted in better 3-year OS and CSS than did SBRT; however, publication bias and heterogeneity may have influenced these findings. In contrast, SBRT produced LC results similar to those of surgery regardless of the extent of surgical resection. These findings may have important clinical implications for patients with comorbidities, advanced age, poor pulmonary reserve, and other factors that may contraindicate surgery.

Keywords:
Carcinoma, Non-Small-Cell Lung/surgery; Radiosurgery; Meta-analysis

Variable	Studies, n	Patients, n	Median (range)
Trials and comparative studies Randomized trial Retrospective, propensity score matching Retrospective, adjustment for prognostic covariates Retrospective, other	1 26 1 2	58 24,917 340 4,196
Total SBRT Surgery		29,511 12,365 17,146
Patients Age SBRT Surgery Female sex, % SBRT Surgery Histology, % Adenocarcinoma SBRT Surgery Squamous cell carcinoma SBRT Surgery			73 (66-82) 72 (65-82) 42 (3-65) 40 (3-62) 47 (9-100) 53 (14-100) 30 (0-46) 31 (0-43)
SBRT Total dose, Gy Fraction, n Dose per fraction, Gy Median BED > 100	30		48 (45-60) 4 (3-12) 14 (5-20)
Follow-up period, months SBRT Surgery			31 (18-58) 43 (16-58)
Clinical stage T1N0 T1-2N0 T1-3N0 Stage I	4 21 4 1	3,334 24,757 620 800
Type of surgery^a Mixed Lobectomy Sublobar resection	10 14 9	772 6,242 10,132
Surgical technique Mixed VATS only	26 4	16,951 195
Chemotherapy, % SBRT Surgery			1 (0-16) 8 (0-15)
Positive lymph node involvement SBRT Surgery			6.5 (1.0-75.7) 11.0 (4.0-37.8)

Categorical moderator variable	Number of studies (patients)	HR (95% CI)	p	Heterogeneity
Categorical moderator variable	Number of studies (patients)	HR (95% CI)	p	I², %	p
Type of surgery Lobectomy Mixed Sublobar resection	7 (4,677) 4 (390) 5 (6,320)	1.47 (1.20-1.69) 1.28 (1.07-1.53) 1.24 (1.06-1.46)	< 0.001 0.007 0.009	66 0 38	0.0001 0.658 0.114
VATS No Yes	26 (16,951) 4 (195)	1.3 (1.2-1.4) 1.7 (1.2-2.3)	0.001 0.002	66 0	0.0001 0.528
Propensity score matching Yes No	26 (24,917) 4 (4,594)	1.37 (1.23-1.54) 1.25 (1.01-1.54)	0.001 0.038	61 38	0.001 0.120
T staging T1 T1-2 T1-3	4 (3,334) 21 (24,757) 4 (620)	1.26 (0.95-1.68) 1.33 (1.18-5.00) 1.3 (1.2 -2.0)	0.106 0.0001 0.048	0 68 0	0.460 0.0001 0.40
Continuous moderator variable	Number of studies (patients)	Intercept	Slope	p
Publication year 2010-2019	30 (29,511)	−3.8	0.01	0.916
Chemotherapy, % (median, 1-8)	12 (19,481)	0.75	−0.02	0.208
Pathological lymph node involvement, % (median, 6.5-11.0)	8 (8,969)	0.82	−0.042	0.279

Categorical moderator variable	Number of studies (patients)	HR (95% CI)	p	Heterogeneity
Categorical moderator variable	Number of studies (patients)	HR (95% CI)	p	I², %	p
Type of surgery Lobectomy Mixed Sublobar resection	7 (4,677) 4 (390) 5 (6,320)	1.34 (1.11-1.61) 1.07 (0.84-1.38) 1.21 (0.96-1.53)	0.002 0.573 0.112	45 0 16	0.09 0.77 0.309
VATS No Yes	4 (195) 26 (16,951)	1.26 (1.02-1.54) 1.24 (1.06-1.44)	0.029 0.006	48 61	0.06 0.001
Propensity score matching Yes No	26 (24,917) 4 (4,594)	1.15 (1.04-1.20) 1.40 (1.18-1.67)	0.017 0.0001	15 0	0.295 0.670
T staging T1 T1-2	4 (3,334) 21 (24,757)	1.12 (0.86-1.46) 1.27 (1.10-1.46)	0.380 0.001	0 30	0.902 0.145
Continuous moderator variable	Number of studies (patients)	Intercept	Slope	p
Publication year 2010-2019	30 (29,511)	−102	0.05	0.447
Chemotherapy, % 0-20%	12 (19,481)	0.54	−0.05	0.922
Pathological lymph node involvement, % 0-22%	8 (8,969)	0.5	−0.02	0.833

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[1] Correspondence to:
Gustavo Arruda Viani. Rua Dr. Rubem Aloysio Monteiro Moreira, 155, CEP 14021-686, Ribeirão Preto, SP, Brasil. Tel.: 55 16 3402-6584. Fax: 55 16 3402-1744. E-mail: gusviani@gmail.com