Anticoagulation management and outcomes in cancer-associated ovarian and renal vein thrombosis: A multicenter retrospective cohort study

Abstract Background: Ovarian and renal vein thromboses (OVT, RVT) are rare in the general population but occur more frequently in patients with cancer. Their optimal management and outcomes remain undefined. Aim: To investigate anticoagulation (AC) management and clinical outcomes in patients with active cancer and OVT or RVT. Methods: We conducted a retrospective cohort study at two tertiary centers (Ottawa, Canada; Rome, Italy), including adult patients (≥ 18 years) with a diagnosis of OVT or RVT and active cancer between June 2019 and December 2023. Patients with tumor thrombus were excluded. All patients were followed for 12 months or until death, whichever occurred earlier. The primary outcome was the 6-month cumulative incidence of recurrent venous thromboembolism (VTE). The primary safety outcome was 6-month cumulative incidence of major bleeding events (defined by ISTH criteria). Secondary outcomes included incidences of clinically relevant non-major bleeding (CRNMB) at 6 months, and recurrent VTE, major bleeding, CRNMB, and mortality at 12 months. Descriptive analyses were performed for the overall cohort and stratified by AC use. Continuous variables were summarized using mean (standard deviation, SD) or median (interquartile range, IQR) as appropriate, and categorical variables as counts and percentages. The 6-and 12-month cumulative incidences were analyzed using the Kaplan-Meier method with 95% confidence intervals (CI), considering death as a competing risk. Results: We included 82 patients with cancer-associated OVT (n=67) and/or RVT (n=25, 10 had concurrent OVT and RVT). The mean (SD) age was 63.4 (11.8), with the majority (n=78, 95%) being female. The most common cancer type was gynecological (n=44, 53.7%), with the majority having advanced stage (III or IV) (n=68, 82.9%). Over 84% of patients received anticancer therapy within 3 months and 83% continued cancer therapy following the index VTE. Most VTE (n=80, 97.6%) were incidental. AC was initiated in 82% of patients (n=67), among whom 80% were given therapeutic doses. The most common type of AC was low-molecular-weight heparin (LMWH, 64.2%), followed by direct oral anticoagulant (31.3%). The median (IQR) time to start AC after diagnosis was 1 (0-11) day, with the median (IQR) duration of AC of 10.8 (5.9-12) months. Three patients had recurrent VTE (two new proximal lower extremity deep vein thromboses and one extension to the inferior vena cava), all occurring within 6 months, resulting in the same overall 6- and 12-month cumulative incidences of recurrent VTE of 3.8% (95% CI, 1.0–9.7). The incidences of recurrent VTE in patients started on AC and no AC were 1.5% (95% CI, 0.1–7.2) (n=1) and 14.3% (95% CI, 2.1–37.7) (n=2), respectively. Similarly, all major bleeding events (n=2) occurred within the first 6 months, with the same overall 6- and 12-month cumulative incidences of major bleeding of 2.5% (95% CI, 0.5-7.9). All major bleeding occurred in anticoagulated patients and on therapeutic doses of LMWH. The 6-month incidence of CRNMB was 3.8% (95% CI, 1.0–9.8) and that of 12 month was 6.6% (95% CI, 2.4-13.7). The 12-month incidence of mortality was 25.2% (95% CI, 16.2–35.2). Interpretation: In this cohort of cancer-associated OVT or RVT, 97.6% were incidental VTE. Most patients were treated with therapeutic AC. The overall incidences of recurrent VTE and major bleeding events were relatively low, and all occurred within the first 6 months. Anticoagulation appeared to be effective but was associated with a modest risk of bleeding complications. Although this study was limited by its retrospective cohort design, small sample size, and wide CIs, it provided valuable data to the limited literature on managing these types of unusual site VTE.