Baseline D-Dimer Predicts Subsequent Venous Thromboembolism in 23,505 Patients with One of 11 Solid Malignancies: An 11-Year Retrospective Cohort Study

Background/Objectives: Venous thromboembolism (VTE) is a major complication of cancer. The predictive performance of baseline D-dimer and factors influencing its levels among patients with cancer remain unclear. We aimed to identify predictors of subsequent VTE development and evaluate the cancer-specific predictive performance of baseline D-dimer. Methods: This retrospective study included 23,505 patients with any of 11 malignancies who underwent baseline D-dimer measurement at initial diagnosis at Gifu University Hospital between January 2015 and December 2025. Patients with pre-existing VTE were excluded. Predictors were identified using logistic regression analyses. Cancer-specific predictive performance was evaluated using receiver operating characteristic analyses, with optimal cutoff values determined by the Youden index. Factors associated with baseline D-dimer were also assessed. Results: The median follow-up was 45.3 months (30.4–59.1 months), during which VTE occurred in 784 (3.3%) patients. Higher baseline D-dimer levels and distant metastasis were independent predictors of subsequent VTE. Cancer type was significantly associated with VTE overall, and breast cancer was associated with lower odds than esophageal cancer. D-dimer performance varied among cancer types, with optimal cutoff values of 0.55–2.35 μg/mL. Older age and higher platelet counts were independently associated with elevated baseline D-dimer levels, whereas a higher cholesterol level was inversely associated. Conclusions: Baseline D-dimer level is an independent predictor of subsequent VTE in patients with cancer. Its predictive performance and exploratory thresholds vary among cancers, suggesting that cancer type should be considered when interpreting baseline D-dimer levels. External validation is required before these cancer-specific thresholds can be applied clinically.