Screening for Occult Cancer in Unprovoked Venous Thromboembolism

Mychal Outlaw, Mercer University College of Pharmacy

According to the American Society of Hematology (ASH), unprovoked deep-vein thrombosis and pulmonary embolism may be an early sign of undiagnosed cancer. Additionally, ASH states that individuals with venous thromboembolism (VTE) are two to four times more likely to be diagnosed with cancer. (1)

According to the American Heart Association (AHA), acute VTE can be the initial sign of an occult malignancy, and patients presenting with idiopathic VTE are more likely to have underlying cancer than those where a secondary cause of thrombosis is obvious. AHA also states that extensive screening for cancer in patients with idiopathic VTE is not routinely warranted. (2)

Design Randomized, controlled trial; N= 862
Objective To assess the efficacy and safety of adding computed tomography (CT) of the abdomen and pelvis to a limited screening strategy for occult cancer
Study Groups Limited occult cancer screening plus CT; n= 423

Limited occult cancer screening; n= 431

Methods Patients were randomly assigned to a screening strategy within 21 days after receiving a diagnosis of venous thromboembolism (VTE). Patients assigned to the limited screening strategy underwent a complete history taking and physical examination, measurement of complete blood counts and serum electrolyte and creatinine levels, liver-function testing, and chest radiography. Patients assigned to limited screening plus CT also underwent comprehensive CT of the abdomen and pelvis. Before CT, patients underwent a bowel preparation with the use of PicoSalax. CT included a virtual colonoscopy and gastroscopy, biphasic enhanced CT of the liver, parenchymal pancreatography, and uniphasic enhanced CT of the distended bladder. CT imaging was standardized. Any abnormal findings detected with the use of either strategy were further investigated as directed by the local treating physician, to confirm or rule out suspected cancer. Patients were followed for 1 year and assessed at fixed intervals with the use of a checklist to elicit information about a new cancer diagnosis, recurrent venous thromboembolism, or other adverse events.
Duration One year
Primary Outcome Measure Confirmed cancer that was missed by the screening strategy and detected by the end of the one-year follow-up period
Baseline Characteristics
Characteristic Limited Occult Cancer Screening         (n= 431) Limited Occult Cancer Screening plus CT (n= 423)
Mean age (years) 53.7 53.4
Male sex, n (%) 277 (64.3) 299 (70.7)
White race, n (%) 395 (91.6) 397 (93.9)
Prior provoked VTE, n (%) 29 (6.7) 18 (4.3)
VTE: Deep vein thrombosis, n (%) 289 (67.1) 287 (67.8)
Medications: Antiplatelet agent, n (%) 21 (4.9) 19 (4.5)
Results Thirty-three (3.9%) patients received a new diagnosis of cancer in the interval between randomization and the one-year follow-up. A total of 14 patients (3.2%) in the limited-screening group and 19 patients (4.5%) in the limited-screening-plus CT group received a diagnosis of occult cancer (P=0.28).
Adverse Events Common Adverse Events: N/A
Serious Adverse Events: N/A
Percentage that Discontinued due to Adverse Events: N/A
Study Author Conclusions This study found that the prevalence of occult cancer was low among patients who had a first unprovoked venous thromboembolism. Routine screening with CT of the abdomen and pelvis did not provide a clinically significant benefit.

The rate of detection and overall prevalence of occult cancer in this study was lower than expected. A potential limitation was that CT of the chest was not included in the screening strategy of limited plus CT because CT pulmonary angiography had been performed in many patients for the diagnosis of pulmonary embolism. The inclusion of this diagnostic test in the limited screening plus CT may have detected more occult cancers than what was reported.

These results suggest that a limited screening strategy for occult cancer may be adequate for patients who have a primary, unprovoked VTE. The study concluded that routine screening with CT of the abdomen and pelvis did not provide a clinically significant benefit. (3)

References

  1. George, Tracy. Computed Tomography Provides No Benefit over Routine Screening for Occult Cancer. American Society of Hematology. 2015. Available at: http://www.hematology.org/Thehematologist/Diffusion/4305.aspx. Accessed August 31,2015.
  2. Lee AY, Levine MN. Venous thromboembolism and cancer: risks and outcomes. Circulation. 2003;107(23 Suppl 1):I17-21.
  3. Carrier M, Lazo-langner A, Shivakumar S, et al. Screening for Occult Cancer in Unprovoked Venous Thromboembolism. N Engl J Med. 2015;
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