Long-term Cardiovascular Mortality Risk in Patients with Bladder Cancer: a Real-world Retrospective Study of 129,765 Cases Based on the SEER Database

Introduction: Among 28 cancer types, bladder cancer (BC) patients have the highest risk of dying from cardiovascular disease (CVD). We aimed to identify the independent risk factors and develop a novel nomogram for predicting long-term cardiovascular mortality in patients with BC.

Methods: We extracted data from the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed with bladder cancer (BC) between 2000 and 2017. The cumulative incidence function (CIF) was computed for both CVD-related death and other causes of death. Then we performed univariate and multivariate analyses to explore the independent risk factors and further develop a novel nomogram to predict cardiovascular mortality at 5- and 10-year for patients with BC by using the Fine-Gray competing risk model. The efficacy of the developed nomogram was assessed by the concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA).

Results: A total of 12,9765 patients were randomly divided into training ( = 90,835, 70%), and validation ( = 38,930, 30%) cohorts. During the follow-up period, 31,862 (46.4%) patients died from BC, and 36793 (53.6%) patients died from non-BC, of which CVD-related death accounted for 17,165 (46.7%), being the major cause of non-cancer deaths. The multivariate analysis showed that age, sex, race, marital status, histologic type, tumor grade, summary stage, and chemotherapy were independent risk factors of CVD-related death in BC patients. The nomogram based on the above eight factors showed good discrimination power, excellent consistency, and clinical practicability: (1) the areas under the curve of the ROC for 5- and 10-year CVD-related death of 0.725 and 0.732 in the training cohort and 0.726 and 0.734 in the validation cohort; (2) the calibration curves showed that the prediction probabilities were basically consistent with the observed probabilities; (3) the DCA curves revealed that the nomogram had high positive net benefits.

Discussion: To our knowledge, this was the first study to identify the independent risk factors and develop a novel nomogram for predicting long-term cardiovascular mortality in patients with BC based on the competing risk model. Our results could help clinicians comprehensively and effectively manage the co-patient of BC and CVD, thereby reducing the risk of cardiovascular mortality in BC survivors.