Abstract
The treatment of esophageal cancer has evolved significantly over the past decade with the emergence of immunotherapy, particularly through the use of immune checkpoint inhibitors (ICIs) such as nivolumab and pembrolizumab. Although gastrointestinal cancers initially showed limited response, recent studies have demonstrated efficacy in selected subgroups, particularly in tumors with high PD-L1 expression or microsatellite instability (MSI-H).
Esophageal cancer consists of two main subtypes: squamous cell carcinoma (SCC) and adenocarcinoma (AC), each with distinct molecular, anatomical and epidemiological characteristic requiring tailored therapeutic approaches. Despite advances in multimodal therapy, overall survival remains low, especially in metastatic disease.
In localized disease, studies such as CROSS and CheckMate-577 have established the role of neoadjuvant chemoradiotherapy followed by surgery, with adjuvant nivolumab now considered standard of care for patients with residual disease. In advanced disease, trials such as KEYNOTE-590 and CHECKMATE-648 have shown survival benefits with the addition of immunotherapy to standard chemotherapy as first-line treatment.
PD-L1 remains a key biomarker for patient selection, although its clinical interpretation is influenced by biological and technical challenges. Furthermore, novel immunotherapeutic strategies involving an�bodies targeing TIGIT, LAG-3, and CTLA-4 are currently under investigation.
In conclusion, immunotherapy has redefined the standard of care in esophageal cancer, offering improved outcomes in specific clinical contexts. However, standardization of biomarker evaluation and direct comparison trials are still needed to optimize therapy selection and patient benefit.