Prognostic impact of cancer therapy–related cardiotoxicity on oncologic outcomes.

e24023 Background: Cancer therapy-related cardiotoxicity is a common complication of modern anticancer treatments and may adversely affect oncologic outcomes by limiting treatment delivery. While cardiotoxicity is well studied as a cardiovascular safety endpoint, its prognostic impact on cancer outcomes remains incompletely defined and appears to vary across cancer types and treatment settings. Methods: We conducted a systematic review (PROSPERO: CRD420261294684) of observational studies evaluating the association between cardiotoxicity and oncologic outcomes. Eligible studies included adults (≥18 years) with solid tumors or hematologic malignancies receiving systemic anticancer therapy, including anthracyclines, HER2-targeted therapies, immune checkpoint inhibitors, cellular therapies, or other agents. Studies were required to report oncologic outcomes stratified by cardiotoxicity status. Cardiotoxicity was defined using study-specific criteria and included left ventricular ejection fraction decline (typically ≥10% to < 50%), clinical heart failure, myocarditis, clinically significant arrhythmias, biomarker elevation, or cardiotoxicity leading to treatment interruption or discontinuation. Primary outcomes were overall survival (OS) and progression-free or disease-free survival (PFS/DFS). Results were synthesized narratively due to heterogeneity. Results: Eight observational studies met inclusion criteria (3,620 patients). Study designs included retrospective cohorts and prospective registries, with sample sizes ranging from 60 to 1,399 patients and median follow-up of 6-72 months. Associations between cardiotoxicity and oncologic outcomes were heterogeneous. Cardiotoxicity was independently associated with worse OS in patients receiving CAR-T therapy (HR 1.85, 95% CI 1.17-2.92; p = 0.009) and in the cohorts experiencing severe cardiotoxicity (HR 10.2, 95% CI 5.5-19.2; p < 0.001). In contrast, adjuvant trastuzumab-treated breast cancer cohorts showed no consistent association between cardiotoxicity and OS (HR 1.68, 95% CI 0.83–3.41; p = 0.148). For DFS or recurrence-free survival, cardiotoxicity leading to treatment interruption was associated with inferior outcomes (HR 1.6, 95% CI 1.1-2.3), while other cohorts showed non-significant trends. Across studies, cardiotoxicity was consistently linked to treatment interruption, dose reduction, or early discontinuation. Conclusions: Cardiotoxicity is associated with adverse oncologic outcomes primarily in patients with severe or clinically overt cardiac events and in intensive treatment settings. Mild or asymptomatic cardiotoxicity, particularly in adjuvant HER2-positive breast cancer, was not consistently associated with worse survival but frequently resulted in treatment modification. Prospective studies using standardized cardiotoxicity definitions are needed to better define prognostic risk.