Risk of Venous Thromboembolism in Patients with Cancer: A Systematic Review and Meta-Analysis

Abstract

Venous thromboembolism in patients with cancer is common, but precise incidence rates in different cancers are not known, making it difficult to target prevention strategies. This study summarizes the existing literature to determine the risk of venous thromboembolism in high- and average-risk groups of patients with different cancers.

Abstract

Background

People with cancer are known to be at increased risk of venous thromboembolism (VTE), and this risk is believed to vary according to cancer type, stage of disease, and treatment modality. Our purpose was to summarise the existing literature to determine precisely and accurately the absolute risk of VTE in cancer patients, stratified by malignancy site and background risk of VTE.

Methods and Findings

We searched the Medline and Embase databases from 1 January 1966 to 14 July 2011 to identify cohort studies comprising people diagnosed with one of eight specified cancer types or where participants were judged to be representative of all people with cancer. For each included study, the number of patients who developed clinically apparent VTE, and the total person-years of follow-up were extracted. Incidence rates of VTE were pooled across studies using the generic inverse variance method. In total, data from 38 individual studies were included. Among average-risk patients, the overall risk of VTE was estimated to be 13 per 1,000 person-years (95% CI, 7 to 23), with the highest risk among patients with cancers of the pancreas, brain, and lung. Among patients judged to be at high risk (due to metastatic disease or receipt of high-risk treatments), the risk of VTE was 68 per 1,000 person-years (95% CI, 48 to 96), with the highest risk among patients with brain cancer (200 per 1,000 person-years; 95% CI, 162 to 247). Our results need to be considered in light of high levels of heterogeneity, which exist due to differences in study population, outcome definition, and average duration of follow-up between studies.

Conclusions

VTE occurs in greater than 1% of cancer patients each year, but this varies widely by cancer type and time since diagnosis. The absolute VTE risks obtained from this review can aid in clinical decision-making about which people with cancer should receive anticoagulant prophylaxis and at what times.

Please see later in the article for the Editors' Summary.

Editors' Summary

Background

A venous thrombosis is the medical term for a blood clot that forms in a vein, often completely blocking the vessel. The most common type is a deep vein thrombosis of the lower leg, which apart from causing pain and immobility, can break off (embolize), flow through the blood stream back to the heart, get caught in one of the blood vessels supplying the lungs, and cause a life-threatening pulmonary embolism. The term venous thromboembolism (VTE) refers to both a deep venous thrombosis and a pulmonary embolism and is a common cause of death, responsible for at least 300,000 deaths a year in the United States alone. There are many risk factors for developing a VTE, including age, immobility, certain medications, and some conditions, such as cancer: an estimated 20% of deaths from VTE occur among patients with cancer, and importantly, cancer patients with VTE have a much higher risk of death than those who do not have a VTE. The increased risk of developing a VTE is due to the treatments and surgery involved in the management of cancer, in addition to the risks associated with the condition itself.

Why Was This Study Done?

Previous studies have suggested that certain types of cancer, such as brain and pancreatic cancer, are associated with an increased risk of developing a VTE, but to date, clinical guidelines recommend preventative treatment of VTE only for cancer patients during hospital admissions for medical treatment and surgery, not for those patients receiving outpatient care. In this study, the researchers systematically reviewed the available published evidence to quantify the risks of developing a VTE in patients with cancer according to the type of cancer, and to determine whether certain patient groups are at particularly high risk of developing a VTE.

What Did the Researchers Do and Find?

The researchers used a comprehensive keyword search of two medical literature databases to identify relevant studies published between 1966 and 2011. Then they examined these studies according to certain criteria, such as the type of study and the type of cancer: the researchers were specifically looking for cohort studies of adult patients with one of eight cancer types—breast, lung, colorectal, prostate, brain, bone, pancreatic, and hematologic (including all leukemias, lymphomas, and multiple myeloma). The selected studies also had to include follow-up of more than 30 days and VTE outcomes. Then the researchers categorized selected studies according to the risk of developing a VTE—the researchers judged high-risk patients to be those with metastatic disease or receiving certain types of high-risk treatments, and judged average-risk patients to be representative of all patients with a cancer diagnosis. The researchers then pooled all the data from these studies and did a separate statistical analysis for high and average risk and for each cancer type.

Using these methods, the researchers identified 7,274 potentially relevant articles, of which 46 reports from 38 individual cohorts met the criteria to be included in their review. Of the 38 cohorts, the researchers categorized 31 as high risk and seven as average risk. In the pooled analysis the researchers found that among average-risk patients, the overall risk of VTE was 13 per 1,000 person-years, with the highest risk among patients with cancers of the pancreas, brain, and lung. Among patients judged to be at high risk, the researchers found that the risk of VTE was 68 per 1,000 person-years, with the highest risk among patients with brain cancer (200 per 1,000 person-years).

What Do These Findings Mean?

These findings suggest that the annual incidence rate of VTE in patients with cancer is between 0.5% and 20%, depending on the cancer type, background risk, and time since diagnosis. Cancers of the brain and pancreas have the highest risk of VTE for both high- and average-risk patient groups. Based on these more accurate data on the risks of VTE in different groups of cancer patients, future updates of clinical guidelines can now include more information about categories of risk to help guide clinicians when they make decisions about which patients should receive preventative treatment for VTE and when they should receive such treatment.

Additional Information

Please access these websites via the online version of this summary at http://dx.doi.org/10. 1371/journal.pmed.1001275.

• Wikipedia gives more information about VTE (note that Wikipedia is a free online encyclopedia that anyone can edit)

• Information about VTE for patients and health professionals is available from the American Cancer Society, the US National Cancer Institute, and the UK-based thrombosis charity Lifeblood