Screening for Occult Cancer in Unprovoked Venous Thromboembolism

Shayne Kreutzer, PharmD Candidate 2016, Mercer University College of Pharmacy

According to the National Comprehensive Cancer Network (NCCN) occult primary tumors, or cancer of unknown primary (CUPs), are defined as histologically proven metastatic malignant tumors whose primary site cannot be identified during pretreatment evaluation. NCCN suggests these heterogeneous tumors have a wide variety of clinical presentation and a poor prognosis in most patients, with an average age of diagnosis of 60 years.1 It is suggested by the NCCN that a baseline computed tomography (CT) scan of the chest, abdomen and pelvis with the use of intravenous contrast material is the standard of care.1, 2 According to Venous Thromboembolism and Cancer: Risks and Outcomes, a diagnosis of cancer is more likely to arise in patients without identified risk factors for thrombosis who present with apparently spontaneous Deep-vein thrombosis (DVT) than in those in whom secondary DVT occurs postoperatively or in another high risk situation, or patients with signs and symptoms of DVT in whom thrombosis is subsequently excluded.3

Title: Screening for Occult Cancer in Unprovoked Venous Thromboembolism
Design Multicenter, open-label, randomized, controlled trial
Objective To determine if extensive screening strategies, (using a screening strategy (e.g., incorporating ultrasonography or computed tomography [CT] of the abdomen and pelvis, measurement of tumor markers, or a combination of these) can substantially increase the rate of detection of occult cancer.
Study Groups Limited occult-cancer screening + CT [423]

Limited occult-cancer screening [431]

Methods Patients with a new diagnosis of first unprovoked symptomatic venous thromboembolism, who were referred to a thrombosis clinic, were potentially eligible to participate.   Patients were randomized using random-number tables. Patients assigned to the limited screening group underwent a complete history taking, physical examination, measurement of complete blood counts, serum electrolyte, creatinine levels, liver-function testing and chest radiography.   Patients assigned to limited screening plus CT underwent comprehensive CT of the abdomen and pelvis. CT imaging was standardized throughout the group.
Duration October 2008 – April 2014; one year of follow-up
Primary Outcome Measure Number of patients with new diagnosis of occult-cancer between the interval between randomization and at one-year follow-up, with a negative screening result for occult cancer
Baseline Characteristics Limited occult-screening Limited occult-screening + CT
Age 53.7 +/- 13.8 53.4 +/- 14.2
Male sex 64.3% 70.7%
White Race 91.6% 93.9%
Deep-vein thrombosis 67.1% 67.8%
Pulmonary embolism 32.9% 32.2%
Deep-vein thrombosis and pulmonary embolism 12.1% 12.5%
Results 33 patients [3.9%; 95% CI] had a new diagnosis of cancer

Limited occult-screening: 14 patients [3.2%; 95% CI]; 4 occult-cancers (29%) were missed

Limited occult-screening + CT: 19 patients [4.5%; 95% CI]; 5 (26%) occult-cancers were missed

A Kaplan-Meier analysis examining the time to detection of a missed occult-cancer over the 1-year follow-up period indicated no significant difference between-group difference [p = 0.87].

No significant difference between the two study groups in the mean time to a cancer diagnosis or in cancer-related mortality.

Adverse Events Common Adverse Events: 0%
Serious Adverse Events: 0%
Percentage that Discontinued due to Adverse Events: 0%
Study Author Conclusions 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 use of a comprehensive CT of the abdomen and pelvis did not lead to fewer missed cancer than those in limited screening without CT. Furthermore, the screening strategy using the CT did not significantly detect more occult-cancers (including early cancers), shorten the time to cancer diagnosis or reduce cancer-related mortality. This study suggests that a limited screening strategy may be adequate for patients who have had their first unprovoked VTE. These results are consistent with two previous trials, showing no statistical difference in either screening groups the patients were a part of.4


  1. Ettinger, David S., M.D. “National Comprehensive Cancer Network.” NCCN. N.p., 15 Sept. 2014. Web. 24 June 2015. <;.
  2. Varadhachary, Gauri R., M.D. “Cancer of Unknown Primary Site.” The New England Journal of Medicine. N.p., 21 Aug. 2014. Web. 24 June 2015. <>.
  3. Lee, Agnes Y., M.D. “Venous Thromboembolism and Cancer: Risks and Outcomes.” Venous Thromboembolism and Cancer: Risks and Outcomes. American Heart Association, 17 July 2003. Web. 24 June 2015. <;.
  4. Carrier, Marc, M.D. “Screening for Occult Cancer in Unprovoked Venous Thromboembolism — NEJM.” New England Journal of Medicine. The New England Journal of Medicine, 22 June 2015. Web. 24 June 2015. <;.

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