Are intra-pleural bacterial products associated with longer survival in adults with malignant pleural effusions? A systematic review

Background: Intra-pleural bacteria are effective pleurodesis agents in malignant pleural effusions. However, their relationship with survival is unclear. Objectives: We undertook a comprehensive, structured evaluation of survival outcomes in adults with malignant pleural effusions treated with intra-pleural bacterial products. Data sources: Medline, Embase, Cochrane library, Clinical Trials Registers and Open Grey. Study eligibility criteria, participants, and interventions: Randomised controlled trials and non-randomised comparative studies were included, if the population included adults with malignant pleural effusions. Interventions of interest were any intra-pleural bacterial product, compared with placebo, alternative intra-pleural drug, or no treatment. Survival outcomes were collected. Study appraisal and synthesis methods: Two reviewers independently screened studies for eligibility, assessed papers for risk of bias and extracted data. Narrative synthesis was performed as high heterogeneity between studies precluded meta-analysis. Results: 631 studies were identified, of which 14 were included. All were at high or unclear risk of bias in at least one domain. Six studies reported a survival benefit associated with intra-pleural bacterial products, whilst 8 reported no difference. Non-randomised studies and studies published prior to 2000 were more likely to report survival benefits. Limitations: There was high heterogeneity between studies, which limited the generalisability of findings. Publication bias may have affected the review as five full-text papers were unobtainable, and survival outcomes were missing in a further five. Conclusions: There is a lack of high quality evidence regarding the relationship between intra-pleural bacterial products and survival. Implications of key findings: Well-designed, prospective randomised trials are needed, to determine whether intra-pleural bacterial products can improve survival in pleural malignancy. PROSPERO registration number: CRD42017058067.