Neoadjuvant therapy and risk of bronchopleural fistula after lung cancer surgery: a systematic meta-analysis of 14 912 patients

Neoadjuvant therapy has been extensively analyzed in studies addressing the risk factors of bronchopleural fistula, but their results vary hugely. Therefore, we conducted this meta-analysis to determine the association between neoadjuvant therapy and risk of bronchopleural fistula in patients undergoing lung cancer surgery. We searched PubMed and EMBASE to identify the full-text literatures that met our eligibility criteria. Odds ratio with 95% confidence interval served as the summarized statistics. Heterogeneity within this meta-analysis was evaluated by Q-test and I (2) statistic. Sensitivity analysis was performed for further assessments of robustness. Publication bias was detected by Begg's test and Egger's test. Thirty studies enrolling 14 912 lung cancer cases were included into this meta-analysis. The incidence of bronchopleural fistula was 2.4% (354/14 912) in the large scale. Overall, neoadjuvant therapy significantly increased the risk of bronchopleural fistula after pulmonary resections (odds ratio: 2.166; 95% confidence interval: 1.398-3.357; P = 0.001). In subgroup analysis, neoadjuvant radiotherapy (odds ratio: 3.914; 95% confidence interval: 1.401-10.935; P = 0.009) and chemo-radiation (odds ratio: 2.533; 95% confidence interval: 1.353-4.741; P = 0.004) were significantly associated with the bronchopleural fistula risk but neoadjuvant chemotherapy was not (odds ratio: 1.857; 95% confidence interval: 0.881-3.911; P = 0.104). The impact of neoadjuvant therapy on bronchopleural fistula occurrence remains statistically prominent in the other subgroups. Neoadjuvant therapy is significantly associated with the occurrence of bronchopleural fistula after lung cancer surgery. Both neoadjuvant radiotherapy and chemo-radiation significantly increase the bronchopleural fistula risk but neoadjuvant chemotherapy does not. Some limitations still exist in this meta-analysis. The updated high-quality studies can help to further confirm and enrich our discoveries in the future.