Effect of testing for cancer on cancer‐ and venous thromboembolism (VTE)‐related mortality and morbidity in patients with unprovoked VTE

Robertson L, Yeoh SE, Stansby G, Agarwal R, Robertson, Lindsay, Yeoh, Su Ern, Stansby, Gerard, Agarwal, Roshan

Venous thromboembolism (VTE) is a collective term for two conditions: deep vein thrombosis (DVT) and pulmonary embolism (PE). A proportion of patients with VTE have no underlying or immediately predisposing risk factors and the VTE is referred to as unprovoked. Unprovoked VTE can often be the first clinical manifestation of an underlying malignancy. This has raised the question of whether patients with an unprovoked VTE should be investigated for an underlying cancer. Treatment for VTE is different in cancer and non-cancer patients and a correct diagnosis would ensure that patients received the optimal treatment for VTE to prevent recurrence and further morbidity. Furthermore, an appropriate cancer diagnosis at an earlier, potentially curative stage could avoid the risk of cancer progression and thus lead to improvements in cancer-related mortality and morbidity. To determine whether testing for undiagnosed cancer in patients with a first episode of unprovoked VTE (DVT or PE) is effective in reducing cancer and VTE-related mortality and morbidity and to establish which tests for cancer are most useful. The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched January 2015) and the Cochrane Register of Studies (CRS) (2014, Issue 12). Clinical trials databases were searched. The reference lists of relevant articles were also checked. Randomised and quasi-randomised trials in which patients with an unprovoked VTE were allocated to receive specific tests for cancer or clinically indicated tests only were eligible for inclusion in this review. Primary outcomes included all-cause mortality, cancer-related mortality and VTE-related mortality. Selection of the studies, quality assessment and data extraction were completed independently by two review authors. Any disagreements were resolved by discussion. Two studies with a combined total of 396 patients met the inclusion criteria for this review. Both studies assessed the effect of testing for cancer versus clinically indicated tests only in patients with an unprovoked VTE. The quality of the evidence was moderate because although the studies were judged to be at low or unclear risk of bias, there was concern that the studies were small as reflected in the wide confidence intervals (CIs). Pooled analysis showed that testing for cancer was consistent with either a benefit or no benefit on cancer-related mortality (odds ratio (OR) 0.49, 95% CI 0.15 to 1.67, P = 0.26). One study showed that, overall, malignancies were less advanced in patients belonging to the extensive screening group than in patients of the control group (64% versus 20%, P = 0.047) and that tested patients were diagnosed earlier than untested patients (mean 1 month versus 11.6 months to cancer diagnosis from the time of diagnosis of VTE). Standard deviations were not provided for time to diagnosis, so it was not possible to perform an independent statistical analysis on this association. Neither study measured all-cause mortality, VTE-related morbidity and mortality, side effects of anticoagulation, side effects of cancer tests or patient satisfaction. Testing for cancer in patients with idiopathic VTE leads to earlier diagnosis of cancer at an earlier stage of the disease. However, there is currently insufficient evidence to draw definitive conclusions concerning the effectiveness of testing for undiagnosed cancer in patients with a first episode of unprovoked VTE (DVT or PE) in reducing cancer and VTE-related morbidity and mortality. The results are imprecise and could be consistent with either harm or benefit. Further good-quality large-scale randomised controlled trials are required before firm conclusions can be made.