Level 2 (mid-level) evidence

Unprovoked venous thromboembolism (VTE), a VTE occurring in the absence of triggering events or risk factors, has been associated with the presence of occult malignancies. The prevalence of undiagnosed cancer 1 year after VTE may be as high as 10%; a systematic review found that, at the time of VTE event, the rate of missed diagnosis was approximately 4%. In those with unprovoked VTE, routine evaluation should include basic cancer workup comprised of history and physical examination, complete blood count, erythrocyte sedimentation rate, renal and liver function tests, urinalysis, and chest x-ray.

The addition of imaging tests (such as computed tomography [CT] or ultrasound) and molecular biomarkers have been proposed to reduce the rate of missed cancer diagnoses at the time of VTE. However, in previous studies that compared the use of limited screening with the use of extensive screening procedures, no significant differences were found in overall cancer detection or in cancer-related mortality. To look at the specific role CT might play in cancer detection, a recent randomized trial compared limited cancer screening plus pelvic and abdominal CT versus limited cancer screening alone in 852 adults (mean age 53 years, 67% male) with first unprovoked symptomatic VTE.

Limited cancer screening included a complete history and physical examination, basic blood tests (complete blood count, serum electrolyte level, creatinine level, and liver function testing), chest x-ray, and sex-specific cancer screening if not performed in the prior year (breast, cervical, and prostate). Pelvic and abdominal CT screening included a virtual colonoscopy and gastroscopy, biphasic enhanced liver CT, parenchymal pancreatography, and uniphasic enhanced distended bladder CT. Of the total patients, 95% completed the 1-year follow-up. Rates of cancer detection at screening were 3.3% with limited screening plus CT versus 2.3% with limited screening alone (not significant).

At 1-year follow-up, 4.5% of patients who had limited cancer screening plus CT and 3.2% of patients who had limited screening alone were diagnosed with cancer, resulting in rates of missed diagnosis at screening of 1.18% and 0.93%, respectively (not significant). These results correspond to 5 of 19 cancers (26%) missed with the more extensive protocol and 4 of 14 cancers (29%) missed with limited screening alone. There were also no significant differences in mean time to cancer diagnosis, recurrent VTE, overall mortality (1.4% vs 1.2%, P=1), or cancer-related mortality (1.4% vs 0.9%, P=.75).

The results of this randomized trial suggest that, after initial cancer screening in those with VTE, the rate of cancers detected during the subsequent year is not enhanced by the use of extensive abdominal and pelvic CT scanning. The key issue is whether extensive screening at initial workup results in a slight increase in the rate of detected cancers. Although not statistically significant, the 1% higher detection rate using extensive screening at initial workup is consistent with results of previous systematic reviews, randomized trials, and other studies that have shown 1% to 2% additional yield for cancer detection when extensive screening was used.

There are, however, significant limitations to the interpretation of these results, including low event rates and wide confidence intervals, which make it impossible to rule out a small benefit associated with CT imaging for cancer detection. Regardless, whether a small increase in cancer detection rate translates to meaningful clinical outcome remains unproven, and the use of multiphasic CT of the abdomen and pelvis includes a risk for subsequent radiation-induced malignancy. This risk has been estimated at 1 in 460 to 500 persons for a 40-year-old person (Arch Intern Med. 2009;169[22]:2078-2086). For now, the use of limited screening, including routine screening for cancer based on age- and sex-based recommendations for the general population, seems appropriate for most patients.

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(8):697-704. doi: 10.1056/NEJMoa1506623

Alan Ehrlich, MD, is a deputy editor for DynaMed, Ipswich, Mass., and assistant clinical professor in Family Medicine, University of Massachusetts Medical School in Worcester. 

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