Testing for cancer in patients with unprovoked venous thromboembolism

There is insufficient evidence as to whether testing for undiagnosed cancer in patients with a first episode of unprovoked venous thromboembolism (VTE) is effective in reducing cancer- and VTE-related mortality and morbidity, and which tests for cancer are most useful.

The quality of evidence is downgraded by study limitations (unclear allocation concealment), and by imprecise results (few patients and outcome events).

Summary

A Cochrane review included 4 studies with a total of 1644 subjects. Four studies with 1644 participants met the inclusion criteria (two studies in the original review and two in this update). Two studies assessed the effect of extensive tests versus tests at the physician's discretion) while the other two studies assessed the effect of standard testing plus positron emission tomography (PET)/computed tomography (CT) scanning versus standard testing alone. For extensive tests versus tests at the physician's discretion, the quality of the evidence was low due to risk of bias (early termination of the studies). When comparing standard testing plus PET/CT scanning versus standard testing alone, the quality of evidence was moderate due to a risk of detection bias. The quality of the evidence was downgraded further when detection bias was present in one study with a low number of events. When comparing extensive tests versus tests at the physician's discretion, pooled analysis on two studies showed that testing for cancer was consistent with either a benefit or no benefit on cancer-related mortality (odds ratio (OR) 0.49, 95% confidence interval (CI) 0.15 to 1.67; 396 participants; 2 studies; P = 0.26; low quality evidence). One study (201 participants) showed that, overall, malignancies were less advanced in extensively tested participants than in participants in the control group. In total, 9/13 participants diagnosed with cancer in the extensively tested group had a T1 or T2 stage malignancy compared to 2/10 participants diagnosed with cancer in the control group (OR 5.00, 95% CI 1.05 to 23.76; P = 0.04; low quality evidence). There was no clear difference in detection of advanced stages between extensive tests versus tests at the physician's discretion: one participant in the extensively tested group had stage T3 compared with four participants in the control group (OR 0.25, 95% CI 0.03 to 2.28; P = 0.22; low quality evidence). In addition, extensively tested participants were diagnosed earlier than control group (mean: 1 month with extensive tests versus 11.6 months with tests at physician's discretion to cancer diagnosis from the time of diagnosis of VTE). Extensive testing did not increase the frequency of an underlying cancer diagnosis (OR 1.32, 95% CI 0.59 to 2.93; 396 participants; 2 studies; P = 0.50; low quality evidence). Neither study measured all-cause mortality, VTE-related morbidity and mortality, complications of anticoagulation, adverse effects of cancer tests, participant satisfaction or quality of life. When comparing standard testing plus PET/CT screening versus standard testing alone, standard testing plus PET/CT screening was consistent with either a benefit or no benefit on all-cause mortality (OR 1.22, 95% CI 0.49 to 3.04; 1248 participants; 2 studies; P = 0.66; moderate quality evidence), cancer-related mortality (OR 0.55, 95% CI 0.20 to 1.52; 1248 participants; 2 studies; P = 0.25; moderate quality evidence) or VTE-related morbidity (OR 1.02, 95% CI 0.48 to 2.17; 854 participants; 1 study; P = 0.96; moderate quality evidence). With regards to stage of cancer, there was no clear difference for detection of early (OR 1.78, 95% 0.51 to 6.17; 394 participants; 1 study; P = 0.37; low quality evidence) or advanced (OR 1.00, 95% CI 0.14 to 7.17; 394 participants; 1 study; P = 1.00; low quality evidence) stages of cancer. There was also no clear difference in the frequency of an underlying cancer diagnosis (OR 1.71, 95% CI 0.91 to 3.20; 1248 participants; 2 studies; P = 0.09; moderate quality evidence). Time to cancer diagnosis was 4.2 months in the standard testing group and 4.0 months in the standard testing plus PET/CT group (P = 0.88). Neither study measured VTE-related mortality, complications of anticoagulation, adverse effects of cancer tests, participant satisfaction or quality of life.

Clinical comments

Date of latest search:

Ədəbiyyat

1. Robertson L, Yeoh SE, Stansby G et al. Effect of testing for cancer on cancer- and venous thromboembolism (VTE)-related mortality and morbidity in people with unprovoked VTE. Cochrane Database Syst Rev 2017;(8):CD010837.