The Incidence and Risk of Venous Thromboembolism in Patients with Active Malignancy and Isolated Superficial Venous Thrombosis: A Systematic Review and Meta-Analysis. (The IROVAM-iSVT review)

Introduction:

The management of cancer-associated isolated superficial venous thrombosis (iSVT) remains a challenge. Some studies have demonstrated up to 25% of patients with active malignancy develop either deep vein thrombosis (DVT) or pulmonary embolism (PE) one year post iSVT. However, guidelines do not provide specific recommendation for patients with active malignancy and iSVT. Thus, we performed a systematic review and meta-analysis to determine the incidence and risk of subsequent VTE in patients with iSVT and active malignancy, with the aim to support clinical decision-making.

Methods:

PRISMA reporting guidelines were followed, and this study’s protocol was pre-registered on PROSPERO (CRD42024550983). Medline and Embase were searched from inception to April 22nd, 2024, without language or geographic restrictions, using keywords “superficial venous thrombosis” and “superficial vein thrombosis”. All studies investigating the prevalence, incidence, odds, or risk of subsequent DVT or PE in adult (>18 years) patients with active malignancy diagnosed with iSVT were included. This study’s primary outcome was to determine the incidence of VTE (PE or proximal DVT) in patients with active malignancy and iSVT and compare this incidence to patients with iSVT without active malignancy. Our secondary outcomes were to determine the incidence of major bleeding, clinically relevant non major bleeding (CRNMB), hospitalization, and death. Using R software (version 4.4.0), incidence rates, odds ratios, and risk ratios were pooled, separately, using random effects model. Incidence was expressed as events per 100 patient years with associated 95% confidence interval (CI). If necessary, the incidence of VTE was calculated and was defined as the combined number of proximal DVTs and PEs in each study divided by the number of patient years in that study.

Results:

Of 1172 records, 8 full-text studies were included totalling 5998 patients, 448 with active malignancy and iSVT. Follow-up across studies was most reported at 3 months post iSVT, with some studies reporting follow-up at up to 1 year. The overall incidence of VTE in patients with active malignancy was 18.2 events per 100 patient years (95% CI 5.2 to 31.2, I²=76%). Across studies, patients with active malignancy and SVT had a higher rate of VTE compared to patients with SVT without active malignancy (RR 2.57, 95% CI 1.78-3.71, I²=0%, P<0.001). Four studies reported the incidence of major bleeding in patients with active malignancy and iSVT. Of these patients, there were 2 major bleeding events per 100 patient years (95% CI 0 to 6.7, I²=59%). Only one study reported CRNMB, with an incidence of 2.6 events per 100 patient years (2 of 77 patients). Only one study reported hospitalization rates. Patients with active malignancy and iSVT had a higher risk of hospitalization due to VTE compared to patients with iSVT without active malignancy (HR 8.87, 95% CI 2.12–37.12, P=0.003), with 3.9% of patients requiring hospitalisation. One study also found patients with iSVT with active malignancy had 10-fold higher risk of death compared to patients with iSVT without active malignancy (RR 10, 95% CI 3.45 to 25, p<0.001). Compared to patients with iSVT without active malignancy, across studies, there were no significant difference in the number of patients treated with anticoagulation or the duration of anticoagulation.

Conclusion:

The rate of VTE is high post iSVT in patients with active malignancy despite treatment. Thus, future studies should investigate the role of extended duration anticoagulation on rates of VTE in this population.