Reporting Bias Leading to Discordant Venous Thromboembolism Rates in the United States Versus Non-US Countries Following Radical Cystectomy: A Systematic Review and Meta-analysis

Abstract

Context: Postcystectomy bladder cancer (BCa) patients are at high risk for developing venous thromboembolism (VTE). The literature varies widely in the reporting of VTE in this population.

Objective: To determine the VTE rate in subjects undergoing radical cystectomy (RC) and highlight specific factors affecting this rate.

Evidence acquisition: This meta-analysis was registered with the International Prospective Register of Systematic Reviews (PROSPERO) database, registration number: CRD42015016776. We queried MEDLINE, the Cochrane Library, Embase, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science. Search terms captured BCa, RC, and VTE. Per the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, abstracts were reviewed for inclusion/exclusion criteria by two reviewers, and disagreements were resolved by a third reviewer. A search of the gray literature and references of pertinent articles was also performed. The date of our last search was December 15, 2014. For unreported data, authors were contacted. Data were abstracted in duplicate and pooled using a random effects (RE) model. Subgroup analyses and meta-regression were performed to determine risk factors for VTE.

Evidence synthesis: We identified 2927 publications, of which 223 met inclusion criteria for this review. A total of 1 115 634 surgeries were performed on patient population (80% men) with a total of 51 908 VTEs. The VTE rate estimated by the RE model was 3.7%. Due to significant heterogeneity, subgroup and meta-regression analyses were undertaken. These revealed a higher rate of VTE in US studies at 4.49% compared with "westernized" non-US studies at 3.43% and "nonwesternized" non-US based studies at 2.50%. Other important modifiers included minimally invasive surgery at 5.54% versus open surgery at 3.55%, and age. The case-fatality rate of pulmonary emboli was 44%.

Conclusions: VTE is common in patients undergoing RC. Reporting of VTE is heterogeneous and the rate varies according to study-level factors, including surgery type and country of origin. Limitations of this study include the preponderance of observational studies in the final analysis and lack of complete reporting of all variables of interest within each study.

Patient summary: In this review, we determined the venous thromboembolism (VTE) rate in postsurgical bladder cancer patients. VTE events did vary significantly among certain subgroups.

Keywords: Bladder cancer; Cystectomy; Deep venous thrombosis; Pulmonary embolism; Venous thromboembolism.

Fig. 1

– Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) flow chart [25].

Fig. 2

– Forest plot of 223 studies showing the pooled VTE event rate using both the fixed and random effects models. CI = confidence interval; VTE = venous thromboembolism.

Fig. 3

– (a) Standard and (b) Duval-Tweedie trim-and-fill funnel plots suggesting studies with higher rates of venous thromboembolism were more likely to be published. RE = random effects.