BACKGROUND: Patients with cancer undergoing systemic therapies have a high risk for venous thromboembolism (VTE). Risk assessment models were developed to select high-risk subgroups that might benefit from primary thromboprophylaxis, yet currently available models reportedly underperform in contemporary cancer treatment populations and risk models across multiple time points throughout therapy are not available. PATIENTS AND METHODS: We, therefore, aimed to validate the Vienna CATScore, a nomogram-based model including tumor type and continuous D-dimer levels, in a prospective cohort study of patients initiating contemporary systemic anticancer therapies. The validity of the model was tested at study inclusion, 3 weeks, and 3 months after start of therapy. RESULTS: Overall, 598 patients were included [49% women, median age 62 years (interquartile range 53-70 years)]. Most patients had stage IV disease (68.2%). The 6-month cumulative incidence of VTE was 9.2% [95% confidence interval (CI) 6.8% to 11.5%]. The Vienna CATScore demonstrated good discriminatory ability (c-statistics: 0.69, 95% CI 0.61-0.76) at study baseline and across all evaluated time points (c-statistics: 0.68, 95% CI 0.63-0.73). Applying a 6-month predicted VTE risk threshold of 8%, the CATScore effectively distinguished between low- and high-risk groups at study inclusion (7.1% versus 15.1% observed VTE risk, P = 0.004) and across all three time points (6.3% versus 13.6% observed VTE risk, P <
0.001). Assuming a 50% risk reduction with thromboprophylaxis, this threshold resulted in a number needed to treat (NNT) of 13 and 15, respectively, in the high-risk group, while the NNT was 28 and 32, respectively, in the low-risk group. CONCLUSIONS: This external validation of the Vienna CATScore confirms its effectiveness in predicting VTE risk in the initial months of state-of-the-art systemic anticancer therapies and across multiple time points.