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

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.