Review of radiotherapy combined with systemic therapy for advanced esophageal cancer: from chemotherapy to immunotherapy era

Advanced esophageal cancer is characterized by poor prognosis and high recurrence rates, even after receiving standard radical treatments. Current treatment guidelines primarily recommend systemic therapy combined with palliative and supportive care for advanced esophageal cancer, particularly in patients with limited functional status. Despite the recent advances, including the introduction of immunotherapy, overall survival of these patients remains limited. Radiotherapy, traditionally used for palliative purposes, is increasingly being explored as an adjunct to systemic therapies, including chemotherapy and immunotherapy, to improve clinical outcomes. This review aims to examine the current literature on the role of radiotherapy combined with systemic therapies for advanced esophageal cancer. The impact of these combined approaches on overall survival (OS), progression-free survival (PFS), and quality of life was analyzed, focusing on patient selection criteria, optimal treatment strategies, and the timing of radiotherapy administration. Studies have shown that radiotherapy combined with systemic therapy may offer survival benefits, particularly in patients with oligometastasis or limited metastatic disease. Furthermore, the synergistic effects of radiotherapy combined with immunotherapy are promising. However, the impact of such a combination need to be further investigated. Nonetheless, various challenges, including lack of consensus on optimal radiotherapy protocols, appropriate sequencing with systemic treatments, and identification of patient populations most likely to benefit, limit the application of this combination therapy. Therefore, large-scale prospective clinical trials are needed to validate these approaches and refine treatment guidelines for improved prognosis and management of patients with advanced esophageal cancer.