Prevalence and Characteristics of Occult Cancer in Patients with Venous Thromboembolism.
Authors: Beckers Marielle M.J. , Schutgens Roger E.G. , Prins Martin H. , Biesma Douwe H. 
Published: April 2020

Abstract
Background: Venous thromboembolism (VTE) can be the first sign of occult cancer. It is still a matter of debate if screening programs for cancer should be encouraged. No one would advocate extensive screening in an at random VTE-population. It is, however, possible that a subgroup of VTE-patients has a relatively high risk for developing cancer.
Objective: To identify a group of patients with a high prevalence of cancer during follow-up (occult cancer).
Results: We retrospectively reviewed the prevalence and type of cancer in 610 consecutive VTE-patients (267 men and 343 women). Mean age of the patients was 51.9 years and the mean follow-up was 50 months. There were 73 cancer cases (overall prevalence 12%): 32 patients were known with active cancer and 14 patients were diagnosed with cancer at presentation with VTE. A total of 27 patients (4.8%; 27/564) had cancer during follow-up. Among patients with VTE secondary to immobilisation, increased estrogens levels or thrombophilia (n=382) the prevalence of cancer was significantly lower compared to the 228 patients with idiopathic VTE (1.5% versus 10%; p&lt;0.001). In the idiopathic VTE group, patients older than 60 years had a relatively high prevalence of occult cancer (OR=2.7; 95% CI 1.0–7.3; as compared to patients &lt; 60). Gender, location of VTE (PE or DVT) and recurrent VTE were not associated with an increased risk for occult cancer. Laboratory tests of erythrocyte sedimentation rate, blood count, liver and renal function did not predict the occurrence of occult cancer. In 142 patients with idiopathic VTE, the D-dimer concentration was measured at presentation using the Tinaquant® quantitative assay (the DD-group). Eleven patients in the DD-group developed cancer within 24 months of follow-up; 9 (82%) had high D-dimer concentration (&gt;4000 μg/L FEU) at VTE-presentation. The two patients younger than 60 years and occult cancer within 24 months both had a D-dimer concentration &gt;4000 μg/L FEU. In patients older than 60 years and cancer within 24 months after idiopathic VTE, 77.8% (7/9) had initial high D-dimer concentration compared to 22.2% (2/9) with low D-dimer concentration (&lt;4000 μg/L FEU). Five patients diagnosed with cancer after 36 months had all low D-dimer concentrations (&lt;4000 μg/L FEU). The relative risk (RR) of cancer during follow-up was determined by calculating the expected number of cancer using the age and sex specific incidence rates of cancer among the general Dutch population (Netherlands Cancer Registry). At 6 months the RR of being diagnosed with cancer was 5.9 (95% CI= 1.6–15.1), at 12 months the RR was 9.1 (95% CI= 3.34–19.8), at 24 months the RR was 3.3 (95% CI= 0.9–8.3) and at 36 months the RR was 1 (95 % CI= 0.03–5.7).
Conclusion: Screening for cancer in patients with VTE may be limited to patients older than 60 years with idiopathic VTE and to patients with high D-dimer concentration (&gt;4000 μg/L FEU). Within 2 years of follow-up patients with idiopathic VTE have the highest risk for being diagnosed with cancer when compared to the general population.