Real-Life Incidence of Cancer Following a First Unprovoked Venous Thrombosis: Results from the Epigetbo Study

Background: Venous thromboembolism (VTE) can be the first manifestation of cancer. Whether screening for an occult malignancy should be systematically performed in patients with unprovoked VTE is a daily challenge for clinicians. Recently, two randomized trials demonstrated that limited cancer screening in patients with a first unprovoked VTE could be the standard of care. However, the one-year incidence of occult malignancy found in these trials was unexpectedly low (4.5%) raising the hypothesis of an inclusion bias. We aimed at estimating the real-life one-year incidence of cancer following a first unprovoked VTE to inform physicians and policy makers in establishing recommendations for cancer screening in VTE patients.

Methods: The EPIGETBO study is an epidemiologic study that aimed to measure the incidence of VTE in the Brest District, France¹. All symptomatic VTE cases (deep vein thrombosis of the lower limb and pulmonary embolism) diagnosed between March 1^st, 2013 and February 28^th, 2014 among the 367,911 inhabitants of the district were recorded and validated by an adjudication committee. A systematic follow-up was planned in order to study patients' outcome. Unprovoked VTE was defined as the absence of surgical procedure, pregnancy, delivery, immobilization, admission to hospital for an acute medical illness in the 3 months preceding VTE or known active cancer. The 1-year cumulative incidence of cancer was estimated using the Kaplan-Meier method. Then, the hazard for occult cancer diagnosis associated with age>60, male sex, and current smoking was assessed by Cox regression.

Results: During the study period, 576 symptomatic validated VTE events were diagnosed in 562 inhabitants of the Brest District. Five patients did not undergo follow-up (4 refusals, 1 aged<18). The VTE event at study entry was unprovoked in 310 patients (55.6%) and this was a first unprovoked VTE event in 257. Patients' mean age was 67.9 ± 2.2 years, 114 (44.3%) were men, 38 (14.8%) had a prior unprovoked VTE event. In the year following VTE, 9 of the 257 patients with a first unprovoked VTE event were diagnosed with cancer, corresponding to an overall 1-year cumulative incidence of occult cancer of 3.68% (95% CI 1.93-6.96). This incidence was 3.78% (95% CI 1.91-7.43) in the 219 patients with a first unprovoked VTE event and no prior history of provoked VTE (8 cancers). In non-smokers, the 1-year incidence rate of occult cancer was 0.81% (95% CI 0.11-5.59) as compared with 8.05% (95% CI 3.92-16.14) in smokers (p=0.004 by log-rank test). In multivariate analysis, age>60 and male sex were associated with a non significant increased risk for occult cancer diagnosis (HR 4.92; 95% CI 0.60-40.30 and 1.42; 95% CI 0.25-8.13 respectively). Conversely, current smoking was independently associated with a significant 11.8-fold increased risk for occult cancer diagnosis (HR 11.80; 95% CI 1.19-116.52). No cancer was diagnosed in patients aged≤50 years.

Conclusion: In this comprehensive real-life epidemiological study, we confirmed that the one-year incidence of occult malignancy following a first episode of unprovoked VTE is low, especially in non-smokers. Current smoking was associated with a higher risk for occult cancer diagnosis; however, even in this patient subgroup, the absolute frequency was no higher than 8%.

¹ Thromb Haemost 2016; Epub ahead of print DOI: 10.1160/TH16-03-0205