P1.059. Calcium-Channel Blocker Use and Survival After Neoadjuvant Therapy for Locally Advanced ESCC

Abstract

Abstract Topic Esophageal Cancer: Adjuvant and Neo-Adjuvant Therapies Background Calcium-channel blockers (CCBs) are commonly prescribed for cardiovascular disease. Beyond hemodynamic effects, experimental studies suggest that CCBs may modulate tumor biology through interference with apoptosis and alterations in proliferative signaling, however, clinical evidence remains inconsistent and may depend on tumor histology and treatment modality.Whether CCB exposure influences outcomes in esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant therapy followed by radical esophagectomy is unclear. We investigated the association between CCB use and survival outcomes in this study. Methods We retrospectively analyzed a prospectively maintained cohort of patients with locally advanced ESCC treated with neoadjuvant chemotherapy (nCT) or chemoradiotherapy (nCRT) followed by curative-intent esophagectomy. Primary endpoints were overall survival (OS) and disease-free survival (DFS). Survival was estimated using Kaplan–Meier curves and evaluated using multivariable Cox proportional hazards models, with prespecified subgroup analyses by neoadjuvant regimen A causal mediation analysis decomposed the association between CCB use and OS into direct effects and indirect effects. Results Among 580 patients, 56 (9.6%) used CCBs, 275 (47.4%) received nCT and 305 (52.6%) received nCRT. Neoadjuvant regimen type was not associated with OS (p=0.745) or DFS (p=0.358). Baseline characteristics were reported as well balanced between CCB users and non-users. Overall, CCB use was associated with worse OS (HR=1.50; p=0.084) and DFS (HR=1.49; p=0.057). In subgroup analysis, CCB use was linked to inferior outcomes after nCRT (OS: HR=1.90; p=0.024; DFS: HR=1.80; p=0.026), with no clear association after nCT. Mediation analysis suggested predominantly indirect effects via DFS in the overall cohort (HR=1.50; p<0.001) and nCRT subgroup (HR=1.90; p<0.001). Conclusion CCB use was associated with inferior survival in ESCC patients receiving neoadjuvant chemoradiotherapy, with mediation analyses suggesting this association operates largely through higher recurrence risk. No consistent association was observed after neoadjuvant chemotherapy. These findings are hypothesis-generating and support prospective validation, treatment-interaction assessment, and mechanistic studies, including evaluation of perioperative factors and complications that could confound or modify the observed associations.