Predictors of recurrent venous thromboembolism and bleeding in patients with cancer: a meta-analysis

Background and Aims Patients with cancer and venous thromboembolism (VTE) have a high risk of recurrent VTE and anticoagulant-related bleeding. This study aimed to identify prognostic factors for these complications. Methods A systematic review was performed for randomized trials and cohort studies evaluating prognostic factors for recurrent VTE or anticoagulant-related bleeding in adult patients with cancer and VTE. Adjusted hazard ratios (aHRs) for factors were pooled using random-effects meta-analysis. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach. Results Thirty-three studies (n = 96 753) were included in the meta-analyses. Factors with high certainty of association with increased risk of recurrent VTE included a previous history of VTE [aHR 1.50 (95% CI 1.08–2.09)], Eastern Cooperative Oncology Group (ECOG) performance status >0 [1.81 (1.34–2.46)] or >1 [2.44 (1.55–3.84)], advanced cancer [1.38 (1.15–1.65)], and specific cancer sites including lung [1.78 (1.29–2.46)], hepatobiliary [2.37 (1.70–3.30)], pancreas [3.20 (2.06–4.96)], and genitourinary [1.38 (1.14–1.67)]. Conversely, recent surgery [aHR 0.56 (95% CI 0.40–0.76)] and breast cancer [0.43 (0.23–0.81)] had a high certainty of association with a decreased risk. Factors with a high certainty of association with an increased risk of anticoagulant-related bleeding included a history of bleeding [aHR 2.41 (95% CI 1.50–3.88)], ECOG performance status ≥2 [2.10 (1.48–2.99)], advanced cancer [1.60 (1.29–1.97)], and cancers of the brain [2.25 (1.64–3.09)], gastrointestinal system [1.74 (1.44–2.11)], genitourinary system [1.90 (1.48–2.45)], and prostate [1.72 (1.26–2.34)]. Conclusions The prognostic factors identified in this meta-analysis should be considered as part of risk stratification frameworks for anticoagulation management in patients with cancer and VTE.