Direct oral anticoagulants-associated bleeding complications in patients with genitourinary cancer and venous thromboembolism: from the COMMAND VTE Registry-2

Background/Introduction Direct oral anticoagulants (DOACs) are widely used to treat cancer-associated venous thromboembolism (VTE). However, bleeding complications associated with DOACs remain a major concern, particularly in patients with genitourinary (GU) cancer or those with gastrointestinal (GI) cancer. Current guidelines recommend low-molecular-weight heparin as the first-line anticoagulation therapy for these patients rather than DOACs. Although several studies have reported on the clinical outcomes of patients with GI cancer, data on those with GU cancer is limited. Purpose This study aimed to evaluate DOAC-associated bleeding complications in patients with GU cancer, using a large-scale observational database of patients with VTE. Methods We analyzed data from the COMMAND VTE Registry-2, which was a multicenter registry enrolling 5,197 consecutive patients with acute symptomatic VTE at 31 centers in Japan between January 2015 and August 2020. Of these patients, 1149 with cancer-associated VTE who received DOACs were identified. After excluding 202 patients with GI cancer, the study population consisted of 947 patients with active non-GI cancer and VTE who were treated with DOACs. Patients were categorized into GU and non-GU cancer groups. The primary outcome measure was major bleeding during anticoagulation therapy based on International Society on Thrombosis and Haemostasis criteria. We used competing risk methods considering all-cause death as a competing risk. Results Of eligible 947 patients, 332 (35%) had GU cancer. Patients in the GU cancer group were more likely to be women and to have a history of major bleeding. Patients in the non-GI cancer group were older, more frequently underweight, and had a higher prevalence of comorbidities, including diabetes mellitus, chronic lung disease, and liver cirrhosis. They were also more likely to be receiving chemotherapy and to have terminal cancer. The cumulative 5-year incidence of major bleeding during anticoagulation therapy was higher in the GU cancer group than that in the non-GU cancer group (16% versus 9.3%, P<0.001) (Figure 1). Even after adjusting for the confounders, the risk of major bleeding showed consistent results with the unadjusted results (adjusted subhazard ratio, 1.79; 95%CI, 1.18-2.72, P=0.007). The most frequent major bleeding site in the GU cancer group was GI (43%), followed by GU (21%) which was 5 times higher in the non-GU group (4.4%). Conclusions In this large real-world VTE registry in the DOAC era, patients with GU cancer had a higher risk of major bleeding during anticoagulation therapy compared with those with non-GI and non-GU cancers. These findings highlight the need for individualized anticoagulation strategies that account for cancer type-specific bleeding risks.