When Effective Therapies Collide: Aorto-Esophageal Fistula After Thoracic Radiotherapy and Anti-VEGF TKI in a...

Advances in systemic therapies have improved survival in metastatic renal cell carcinoma (mRCC), leading to a growing population of long-term survivors who may receive both radiotherapy (RT) and tyrosine kinase inhibitors (TKIs) during their disease course. Both treatments induce vascular and mucosal toxicity, and their biological effects may overlap, increasing the risk of rare but life-threatening complications such as aorto-esophageal fistula (AEF). Herein, we present the case of a 47-year-old man with mRCC treated with nephrectomy and repeated pulmonary metastasectomies, followed by sunitinib, mediastinal stereotactic body radiotherapy (SBRT), and later cabozantinib for hepatic progression. Five years after thoracic RT and shortly after initiating cabozantinib, the patient developed massive hematemesis due to an AEF. Management included thoracic endovascular aortic repair (TEVAR), esophageal stenting, and prolonged antimicrobial therapy. Despite initial stabilization, recurrent fistulization and infections led to progressive deterioration and death 7 months later. This case underscores the catastrophic potential of RT-TKI interaction in long-term survivor patients. Sequential exposure can transform subclinical vascular injury into fatal outcomes. Risk stratification, nonconcurrent scheduling of RT and anti-VEGF therapy, and vigilant long-term monitoring are essential. Integration of multidisciplinary and palliative approaches is necessary to balance treatment efficacy with safety.