Cancer and clots: All cases of venous thromboembolism are not treated the same
ABSTRACTIdiopathic venous thromboembolism (VTE) can be the first sign of cancer, although how extensively one should search for cancer in a patient with idiopathic VTE is not clear. Treating VTE is more complex in cancer patients than in those without cancer. The authors discuss their approach to searching for undiagnosed cancer in patients with idiopathic VTE and to managing VTE in patients with cancer.
KEY POINTS
- We recommend judiciously screening for cancer with age- and sex-specific tests in patients with idiopathic VTE.
- Patients with VTE and cancer have a higher risk of both VTE recurrence and bleeding complications of anticoagulant therapy than do VTE patients without cancer.
- Either unfractionated heparin or a low-molecular-weight heparin (LMWH) should be started as soon as VTE is confirmed or even strongly suspected, while still awaiting confirmation.
- The current (grade 1A) recommendations for treating VTE in cancer patients are to use LMWH monotherapy for at least 3 to 6 months. Anticoagulation is necessary indefinitely when there is ongoing cancer treatment or persistent risk of VTE.
Venous thromboembolism (VTE) has various differing causes, so its treatment is not necessarily the same in all cases. Most cases of VTE are related to an easily identified risk factor. In patients with an apparently idiopathic event, identifying an underlying cause may alter therapy. In particular, identification of a malignancy may affect the choice of therapy and the duration of treatment.
In this review, we explore the role of cancer screening in patients with idiopathic VTE, then highlight the treatment for VTE in patients with cancer.
‘IDIOPATHIC’ VTE CAN BE DUE TO CANCER
Most patients with venous thrombosis have one of the components of Virchow’s triad: a hypercoagulable state, venous injury, or venous stasis. Those without identifiable risk factors for VTE are considered to have idiopathic VTE. In these patients, a search for a contributing factor may be indicated.
In 1861, the astute clinician Dr. Armand Trousseau noted a link between deep venous thrombosis and pancreatic cancer, stating that if cancer of an internal organ is suspected but the diagnosis cannot be verified, the diagnosis may be confirmed by the sudden, spontaneous appearance of thrombophlebitis in a large vein.1
Today, from 2% to 25% of patients with idiopathic VTE are found to have cancer within 24 months of the diagnosis of VTE.2–11 The goals of cancer screening in idiopathic VTE are to detect cancer at an early, treatable stage and to optimize the VTE therapy to decrease the risks of recurrence and anticoagulation-associated complications in patients who are found to have cancer. However, several questions must be considered first:
- What are the risks and costs of the screening?
- Will discovering the cancer sooner benefit the patient in terms of survival?
- If cancer is found, what are the possible complications or risks of the additional procedures, interventions, or treatments required?
- What is the psychological impact of the screening?
EVIDENCE SUPPORTING CANCER SCREENING AFTER IDIOPATHIC VTE
Piccioli et al12 recently performed a randomized, controlled trial comparing cancer-related death rates in 99 patients with idiopathic VTE screened for malignancy vs 102 patients with idiopathic VTE who were not screened.
The screened group underwent:
- Abdominal and pelvic ultrasonography and computed tomography (CT)
- Gastroscopy or double-contrast barium-swallow evaluation
- Colonoscopy or sigmoidoscopy followed by barium enema
- Testing for fecal occult blood
- Sputum cytology
- Measurement of carcinoembryonic antigen, alpha-fetoprotein, and cancer antigen 125.
- Mammography and Papanicolaou smears (women)
- Ultrasonography of the prostate and prostate-specific antigen testing (men).
Patients were followed for 2 years. The screening uncovered cancer in 13 patients. Cancer developed in one other patient in the screening group during follow-up; in the control group, 10 patients developed symptomatic cancer during follow-up. Overall, the time to cancer diagnosis was 11.6 months in the unscreened group vs 1 month in the screened group (P < .001). Nine of the 14 patients with cancer in the screened group had T1 or T2 disease without local or distant metastasis vs 2 of the 10 control patients with cancer (P = .047). Unfortunately, this study did not have adequate power to detect the effect of screening on survival.
Di Nisio et al13 used data from this trial to perform a decision analysis for cancer screening. They calculated that abdominal and pelvic CT, with or without mammography and with or without sputum cytologic testing, would cost the least per life-year gained and would harm the fewest number of patients. They also suggested that substituting CT of the chest for sputum cytology may provide additional diagnostic benefit.
However, this strategy has not been clinically tested. Given the limited number of patients and the short follow-up in this initial trial, larger trials are needed to look at the cost-effectiveness of this screening model and whether it increases survival.
Our recommendations
Because the data are limited, our approach to looking for an early, treatable malignancy in patients with idiopathic VTE follows the current consensus:
- A thorough history and physical, including an extensive review of systems
- Basic laboratory testing with a complete blood cell count, comprehensive metabolic profile, and urinalysis
- Chest radiography
- Other age- and sex-specific cancer screening tests.
Adding CT of the abdomen, pelvis, or chest to this evaluation may be considered. However, tumor marker testing, which typically has high false-positive rates, is not routinely warranted.13 Additional investigation should be considered if abnormalities are detected during the initial evaluation or in patients with recurrent VTE during therapy.
While this strategy may be most cost-effective, Monreal et al14 suggest that it may miss up to half of cancers ultimately discovered.
