Cancer screening tests in unprovoked DVT

Deep vein thrombosis (DVT) is a frequent diagnosis and the treatment with anticoagulation is well established. It is also known that there are several factors that predispose to the development of DVT - pregnancy, oral contraception, immobility, recent surgery, trauma etc. Where one of these is present it is reasonable to assume that it is the cause. Where there is no obvious provoking factor, concern often surfaces about the possibility of occult malignancy. The extent to which this possibility should be pursued by imaging or other screening procedures gives rise to uncertainty and concern among patients and physicians alike.

This important clinical question was adressed recently by Carrier et al in the New England Journal of Medicine. Unprovoked cases make up more than 40% of all venous thromboembolisms. Epidemiologic studies have consistently shown that a portion of unprovoked events are associated with undiagnosed cancer, with rates of cancer diagnosis in the 12 months following DVT ranging from 5-10%.

Subjecting patients to an extensive diagnostic workup could alter their clinical course: an earlier cancer diagnosis might lead to earlier and more effective treatment and would aslo affect the choice of anticoagulant. Previous studies investigating the effect of extensive testing for cancer in this context have been inconclusive. A 2015 Cochrane systematic review identified only two studies with enough patients to reach statistical conclusions. The review concluded that there was insuffcient evidence about the effectiveness of testing for undiagnosed cancer in reducing cancer-related and VTE-related morbidity and mortality, and that the results could be consistenet with either harm or benefit. 

Carrier et al randomly assigned patients across nine Canadian centres to either a limited screening strategy involving standard age- and sex-specific screening or to an extensive strategy that added computed tomography (CT) of the abdomen and pelvis. This was a sophisticated CT scan that included a virtual colonoscopy and gastroscopy as well as parenchymal pancreatography. Among 854 patients, 3.2% of the patients in the limited-screening group and 4.5% of the patients in the extensive-screening group had a new diagnosis of cancer between randomisation and the one-year follow up. These rates were lower than anticipated. The primary outcome of the study was the number of cancers 'missed' at the initial screening but diagnosed by the end of the one-year follow-up period. Only four patients (0.93%) in the limited-screening group and five (1.18%) in the extensive-screening group had a cancer detected after the completion of the initial screening. Thus the risk of suvsequent cancer was also quite low, and more extensive investigation did not lead to earlier cancer detection. Further analysis found no significant between-group differences in the time to cancer diagnoiss, overall mortality, or cancer-related mortality. 

The conclusion is that patients with unprovoked DVT should have cancer screening tests that would normally be appropriate to their age and gender - mammography, rectal examination and faecal occult blood testing with or without screening colonoscopy. Additional testing is unlikely to provide benefit and may cause harm by exposing the patient to unnecessary radiation.

Reference

1. Carrier M, Lazo-Langner A, Shivakumar S et al. Screening for occult cancer in unprovoked venous thromboembolism. N Engl J Med 2015; 373: 697-704