The incidence and risk factors of newly-diagnosed cancer after diagnosis of venous thromboembolism: from the COMMAND VTE Registry-2

Background/Introduction Venous thromboembolism (VTE) may be the earliest sign of cancer, although there are no established screening strategies for occult cancer. This could be partly due to lack of the real-world incidence and risk factors of occult cancer after diagnosis of VTE in the current era. Purpose The current study aimed to evaluate clinical characteristics and outcomes between patients who were newly diagnosed with cancer after diagnosis of VTE and those who were not, and investigate incidence and risk factors of newly-diagnosed cancer after diagnosis of VTE, using a large-scale multicenter observational database of patients with VTE. Methods The COMMAND VTE Registry-2 is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020. The current study population was consisted of 3706 patients without known active cancer at diagnosis of VTE, who were divided into patients with newly-diagnosed cancer after diagnosis of VTE (N=250, 6.7%) and those without (N=3456, 93.3%). To explore risk factors of newly-diagnosed cancer, we constructed the multivariable Cox proportional hazard model which consisted of variables with P values <0.05 in univariate analysis. Results The cumulative incidences of newly-diagnosed cancer were 1.5% at 30-day, 3.7% at 1-year, 7.0% at 3-year, 11.1% at 5-year, and 16.0% at 7-year. The most common types of newly-diagnosed cancer was colon (17.2%), followed by lung (14.8%) and blood (8.0%). Patients with newly-diagnosed cancer were older (71.6 vs. 67.2 years, P<0.001) and had lower body mass index (22.9 vs. 23.8 kg/m2, P=0.004) than those without. Patients with newly-diagnosed cancer more frequently had several comorbidities such as history of cancer (35% vs. 11%, P<0.001), hypertension (51% vs. 44%, P=0.04), diabetes mellitus (21% vs. 16%, P=0.03), and autoimmune disorder (20% vs. 13%, P=0.004), whereas they less frequently had transient provoking risk factors for VTE (29% vs. 39%, P<0.001). The cumulative incidence of all-cause death was significantly higher in patients with newly-diagnosed cancer than those without (59.3% vs. 21.0% at 7-year). The multivariable Cox proportional hazard model revealed that old age (hazard ratio [HR]: 1.02 per 1 year [1.01-1.03], P<0.001), history of cancer (HR: 3.60 [2.75-4.67], P<0.001), autoimmune disorder (HR: 1.51 [1.09-2.05], P=0.01), and absence of transient provoking risk factors for VTE (HR: 1.36 [1.03-1.80], P=0.03) were independently associated with newly-diagnosed cancer after diagnosis of VTE. Conclusions In the current era, the incidence of newly-diagnosed cancer was 3.7% at 1-year with initial acute increase followed by continuous increase, and several independent risk factors were identified, which might be useful for consideration of optimal screening strategies for occult cancer based on individual risk.Newly-diagnosed cancer