Risk of recurrent venous thromboembolism according to malignancy characteristics in patients with cancer-associated thrombosis: a systematic review of observational and intervention studies

Abstract

Patients with cancer-associated venous thromboembolism (VTE) should be treated with low molecular weight heparin. The ideal duration of anticoagulation in this population is unknown. It is important to evaluate whether there is variation in susceptibility for recurrent VTE according to malignancy characteristics. In this systematic review we sought to evaluate cancer characteristics that may influence the risk for VTE recurrence and the success of anticoagulation in patients with cancer-associated VTE. A systematic literature search strategy identified potential studies on MEDLINE, Embase, the Cochrane Register of Controlled Trials, MEDLINE In-Process and other nonindexed citations using the Ovid interface. There was no restriction to study design or language. No randomized controlled trials fulfilled our inclusion criteria. We included four retrospective and six prospective studies. VTE recurrence rate according to tumour stage suggested an increased risk for patients with metastatic malignancy compared with patients with localized disease (relative risk 1.36; 95% confidence interval 1.06-1.74, P = 0.01). We were unable to pool data to evaluate VTE recurrence according to tumour site and histology. The isolated evaluation of the included studies suggested that younger patients with adenocarcinoma, lung or gastrointestinal malignancy have the highest risk. There is paucity of data regarding detailed malignancy characteristics in patients with cancer-associated VTE. It appears that metastatic malignancy, or adenocarcinoma, or lung malignancy confers a higher risk of VTE recurrence than patients with localized malignancy, nonadenocarcinoma or breast cancer.

Development of a Clinical Prediction Rule for Risk Stratification of Recurrent Venous Thromboembolism in Patients With Cancer-Associated Venous Thromboembolism

“…Our systematic review also suggested that patients with cancer-associated thrombosis do indeed have varying VTE recurrence risk influenced by malignancy characteristics, with metastasis (relative risk, 1.36; 95% CI, 1.06 -1.74; Pϭ0.01) and lung or gastrointestinal malignancies increasing the risk of recurrence and with patients with breast cancer and hematologic malignancies presenting with a lower risk. 13 The present study has potential limitations. The first derived model could not be fully tested in the data from the randomized trials used for external validation, and the scoring system that groups stages I and II as a single variable appears to be less discriminatory than our original model, which suggests an advantage to classifying patients' tumor stage as TNM stage I versus stage II, III, and IV.…”

“…We recently reported a systematic review that suggested that patients of younger age (Ͻ65 years old) or with metastatic malignancy or lung malignancies sustain the greatest risk for recurrent VTE during the anticoagulation period, whereas patients with breast or hematologic malignancies have the lowest risk. 13 These data suggest the potential for the development of a clinical prediction rule for stratification of a patient's risk for the development of a recurrent VTE during the anticoagulation period. Clinical prediction rules are appealing because they offer several potential benefits for practitioners, patients, and the healthcare system, such as a reduction in clinical uncertainty at the bedside and improvement of quality of care for patients.…”

Predictors of venous thromboembolism recurrence and bleeding among active cancer patients: a population-based cohort study

“…This finding is supported by a post hoc analysis of a clinical trial and a systematic review that found an increased recurrence risk among cancer patients with metastatic cancer compared with localized disease. 15,39 A systematic review that included 2 evaluable studies found a 1.4-fold increased risk for recurrence for metastasis compared with no metastasis, but available data were insufficient to control for cancer site or stage. 15 Although most of our patients with stage IV cancer had metastatic disease, we also categorized acute leukemias and brain cancer as "stage IV" cancer for the purposes of analyses (see supplemental Appendix), which likely accounts for our identification of stage IV cancer rather than "metastases" or "metastases location" as independent predictors of recurrence.…”

“…15,39 A systematic review that included 2 evaluable studies found a 1.4-fold increased risk for recurrence for metastasis compared with no metastasis, but available data were insufficient to control for cancer site or stage. 15 Although most of our patients with stage IV cancer had metastatic disease, we also categorized acute leukemias and brain cancer as "stage IV" cancer for the purposes of analyses (see supplemental Appendix), which likely accounts for our identification of stage IV cancer rather than "metastases" or "metastases location" as independent predictors of recurrence. To our knowledge, we are the first to identify cancer stage progression and neurological disease with leg paresis as independent predictors of VTE recurrence among patients with active cancer; leg paresis is a known risk factor for incident VTE.…”

“…9,10 However, patients with cancer also have a high risk for anticoagulant-associated major bleeding, 2,5,[11][12][13][14] such that secondary prophylaxis for all patients with active cancer and incident VTE may be inappropriate. Independent predictors of VTE recurrence among patients with cancer are uncertain 15 ; patient sex; brain cancer among women; lung, gastrointestinal, and genitourinary cancer; myeloproliferative disorders; tumor stage; adenocarcinoma; metastasis; and chemotherapy all have been suggested as predictors of VTE recurrence, 1,5,7,9,[15][16][17][18] but no studies have comprehensively tested all of these characteristics. To address this important gap in knowledge, we conducted a population-based historical cohort study of patients with active cancer and incident VTE to estimate VTE recurrence, estimate bleeding while receiving anticoagulation therapy, estimate survival after VTE recurrence and bleeding, and test baseline cancer and noncancer characteristics and secondary prophylaxis as potential predictors of VTE recurrence and bleeding.…”