Prognosis of Cancers Associated with Venous Thromboembolism
abstract & commentary
Synopsis: There was a higher mortality in patients diagnosed with cancer at the time of or within one year of the thromboembolic event. There was a higher association of distant metastasis at the time of diagnosis in this group as well.
Source: Sorensen HT, et al. N Engl J Med 2000;343:
1846-1850.
It has long been known that malignancy increases the risk of a venous thromboembolism (VTE). In fact, the incidence of cancer after such an event is higher than in the general population. Little is known, however, of the prognosis if the malignancy is discovered at the time of or after the event. This study tries to answer this question and evaluates the association between a history of thromboembolism and the extent of disease at the time of diagnosis.
Henrik and colleagues conducted a retrospective case-control study using data retrieved for the Danish National Registry of Patients from Jan. 1, 1977, to Dec. 31, 1992. Exclusion criteria included previous diagnosis of cancer, surgery within six months of the event, secondary diagnosis of venous thromboembolism, pregnancy, or childbirth within nine months. The remaining patients had demographic and clinical data collected including extent of disease at the time of diagnosis. Patients were divided into those diagnosed at the time of the initial event, within the first year of the initial event, or 1-17 years after the event. The 3135 patients were matched with approximately 10 times the number of controls.
Patients diagnosed with cancer at the time of the thromboembolism had a higher risk of distant metastasis (44%) when compared to controls (35%). For those diagnosed within one year, the risk was 39.6% compared to 32%. For those diagnosed after one year, the risk of distant metastasis was not significantly higher. A comparison of mortality showed similar results. In the first group, the one-year mortality was 78% in cases compared to 64% of controls. The mortality ratio was 2.46 in the first year and 2.2 over the entire period. For patients in the second group, the one-year mortality was 62% in cases compared to 53% of controls. The mortality ratio was 1.35 over the first year and 1.3 over the entire period. The mortality rates for the third group were 47% in cases compared to 45% of controls. The mortality ratio was 1.08 for the first year and 1.1 thereafter. All differences up to one year were statistically significant at the P less than 0.05 level.
Sorensen and colleagues conclude that patients diagnosed with cancer at the time of a thromboembolic event have a poorer prognosis and are more likely to have advanced disease. These risks are evident if cancer is diagnosed within one year of the event as well. These risks are not significant in those diagnosed after one year of the event. These findings may indicate that venous thromboembolism in a patient diagnosed with cancer suggests the presence of advanced and aggressive disease. Sorensen et al suggest that because there is evidence that the pathways of coagulation and tumor growth intersect, prolonged anticoagulation therapy may be of benefit in this population.
COMMENT BY DAVID OST, MD, & DHEERAJ KHANNA, MD
The increased risk of VTE in cancer patients is well known. There is growing evidence to support that patients with VTE are at higher risk for malignancy, especially within the first six months to two years.1-3 This risk is present whether the initial event is a primary deep vein thrombosis or pulmonary embolism.3 Whether VTE will be the first manifestation of malignancy depends on the type of cancer. In a study by Monreal et al, VTE on presentation was found more often in prostate and pancreatic cancer, while it was more often a terminal event in malignancies of the lung, breast, uterus, and brain.4
The present study suggests that venous thromboembolism in patients with cancer is associated with more aggressive disease and a poorer prognosis. Aggressive cancer screening of patients who have idiopathic VTE has not been shown to be cost effective. However, prolonged anticoagulation may be of benefit.2
References
1. Nordstrom M, et al. BMJ 1994;308:891-894.
2. Schulman S, Lindmarker P. N Engl J Med 2000;342: 1953-1958.
3. Sorensen HT, et al. N Engl J Med 1998;338:
1169-1173.
4. Monreal M, et al. Thromb Haemost 1997;78:
1316-1318.
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