Top Papers Of The Month

Unprovoked Clots and Cancer: It’s About Evidence, Cost Savings, and Patient Benefit

Gregory W. Rutecki, MD

Let’s set the stage: Unprovoked deep venous thromboemboli account for 40% of all bouts of thromboembolism.1 One study demonstrated that a standardized incidence ratio of 1.3 unprovoked clot events are seen 1 year before a cancer diagnosis. The next question is obvious: Should all folks with unprovoked events be screened from head to toe for cancer? This month’s Top Paper2 does a great job answering that question.

In the study, 854 patients were randomly assigned to 1 of 2 groups. The first group got limited screening for cancer in unprovoked thromboemboli—that is, basic blood tests, chest radiography, and screening for breast, cervical, and prostate cancers. The second group received the same screening measures, plus computed tomography (CT) of the abdomen and pelvis. The primary outcome measure in the study was a confirmed cancer that had been missed by the screening strategy and that had been detected by the end of a year of follow-up.

Overall, 33 patients (3.9% of the group) received a new diagnosis of cancer. The cancer diagnosis was made in 14 of 431 participants (3.2%) in the limited-screening group, and 19 of 423 participants (4.5%) who had a CT scan added to the limited screening. Another observation shows how close to the 2 groups were: 4 occult cancers (29%) were missed in the limited-screening group versus 5 occult cancers (26%) missed by limited screening plus CT scanning. The study results also showed no differences in the time to cancer diagnosis, overall mortality, or cancer-related mortality between the 2 randomized groups.

This is an important study. Prior to its publication, a Cochrane Database systematic review could find only 2 studies on the subject, with a combined enrollment of 396 participants.3 Despite the paucity of data, the bottom line was that the authors of the Cochrane review agreed that there was insufficient evidence of looking far and wide for cancer in these individuals.

This Top Paper does have some shortcomings. The participants in both groups were relatively young (average, 54 years); if they had been older, there might have been more cases of cancer. What’s more, chest CT was not used, only abdominal and pelvic CT. And only 6.7% of the participants who were 50 years of age or older had had a requisite colonoscopy.1 This is an abysmal number for a screening procedure that has been proven to prevent colon cancer deaths.

Board examination questions frequently ask, in myriad clinical scenarios, whether a search for cancer should be undertaken and, if the answer is yes, how extensive that search should be. Traditional teaching has been that recommended health maintenance screening only is indicated. Yes, that means colonoscopy! Some have strayed from that path.

The editorialist whose article accompanied this Top Paper is right: Less is more.1 When we do not go on a fishing expedition for cancer after a thromboembolic event, we are not harming our patients, and we are not wasting money! But if we ignore routine screening in everyone, we imperil our patients.


Gregory W. Rutecki, MD, is a physician at the National Consult Service at the Cleveland Clinic. He is also a member of the editorial board of Consultant. Dr Rutecki reports that he has no relevant financial relationships to disclose.


  1. Khorana AA. Cancer workup after unprovoked clot—less is more. N Engl J Med. 2015;373(8):768-769.
  2. Carrier M, Lazo-Langner A, Shivakumar S, et al; SOME Investigators. Screening for occult cancer in unprovoked venous thromboembolism. N Engl J Med. 2015;373(8):697-704.
  3. Robertson L, Yeoh SE, Stansby G, Agarwal R. Effect of testing for cancer on cancer- and venous thromboembolism (VTE)-related mortality and morbidity in patients with unprovoked VTE. Cochrane Database Syst Rev. 2015;3:CD010837.