Blood Clots and Buried Cancers

Published - Written by Rena Xu

Insight post 8-19-15An unprovoked blood clot presents a dilemma. Deep vein thrombosis or pulmonary embolism may be the presenting sign of occult cancer, which makes it tempting to search high and low for a source. Early detection could enable prompt treatment and perhaps a better prognosis, in addition to changing the type of anticoagulation a patient receives. On the other hand, exhaustive screening is expensive and, when imaging is involved, exposes patients to radiation that can actually induce cancer. What’s more, there hasn’t been strong evidence historically to suggest that more comprehensive screening translates to fewer missed malignancies.

The NEJM recently reported the results of a large multicenter study that makes a case against more aggressive screening. The Screening for Occult Malignancy in Patients with Idiopathic Venous Thromboembolism (SOME) trial randomized over 850 patients with an unprovoked clotting event to undergo either limited cancer screening – basic labs, a chest x-ray, mammography and Pap smears for women, PSA testing for men – or those tests plus a comprehensive CT scan of the abdomen and pelvis. This scan included virtual colonoscopy and gastroscopy, as well as multi-phased imaging of the liver and pancreas. The primary study endpoint was the number of missed cancers after one year (most occult malignancies get diagnosed within that time frame after a clotting event).

In the two study arms, similar percentages of patients were diagnosed with cancer in the first year (3.2% in the limited screening arm, versus 4.5% in the limited-screening-plus-CT arm). In the limited screening arm, 4 out of 14 cancers, or 29%, were missed by the initial screening. In the limited-screening-plus-CT arm, a similar proportion of diagnoses were missed – 5 out of 19 cancers, or 26%. There was also no difference between the two groups in the average time to diagnosis, which for both groups was around four months.

“In our trial, a screening strategy for occult cancer that included comprehensive CT of the abdomen and pelvis did not lead to fewer missed cancers than the number missed with a limited screening strategy,” the authors write. For patients with a negative result at the time of limited screening, the incidence of a cancer diagnosis later in the first year was less than 1% — similar to the reported incidence among patients without clot.

Previous studies have suggested that in the year after an unprovoked clot, up to 10% of patients are diagnosed with cancer. In this study, across the two groups, the proportion of patients diagnosed was just under 4%. In an accompanying editorial, Dr. Alok Khorana of the Cleveland Clinic suggests that a relatively younger study patient population could have contributed to this discrepancy. The average age of participants in the SOME trial was 54 years; in contrast, in a prior study of over 500,000 patients, the average patient was more than a decade older. The authors, in turn, suggest that the actual prevalence of occult cancer could be decreasing due to better cancer screening.

“Routine screening with CT of the abdomen and pelvis did not provide a clinically significant benefit,” the authors conclude. It’s possible that adding other forms of imaging would have changed these findings, although a third of study participants also got a CT chest as part of their workup for pulmonary embolism. And among the occult cancers most frequently missed were gynecologic tumors and colorectal tumors; if a comprehensive CT scan of the abdomen and pelvis was unable to make the diagnosis in these patients, it seems unlikely that routine imaging of other regions of the body would have helped.

How do you screen patients for malignancy after an unprovoked clot? When would you perform a CT scan as part of your work-up? What other studies, if any, would you consider?