In recent years, the treatment of esophageal cancer has witnessed revolutionary breakthroughs with targeted therapy and immunotherapy.
I. Targeted Therapy
Targeted therapy should be selected for appropriate patient populations based on genetic testing results.
Trastuzumab (Herceptin): An anti-HER2 monoclonal antibody indicated for HER2-positive patients. The ToGA trial demonstrated that chemotherapy combined with trastuzumab extended overall survival in HER2-positive patients from 11.8 months to 16.0 months.
Ramucirumab: A humanized monoclonal antibody that specifically blocks vascular endothelial growth factor receptor 2 (VEGFR2). It is used as monotherapy or in combination with paclitaxel for advanced gastric cancer or gastroesophageal junction adenocarcinoma that has progressed following prior fluoropyrimidine- or platinum-containing chemotherapy.
Nimotuzumab: A monoclonal antibody targeting the EGFR pathway, indicated for advanced esophageal squamous cell carcinoma with high EGFR expression.
II. Immunotherapy – The Greatest Breakthrough
Immunotherapy, represented by PD-1/PD-L1 inhibitors, has significantly improved survival benefits in patients with esophageal cancer.
Pembrolizumab (Keytruda): The KEYNOTE-181 study demonstrated that in PD-L1-positive patients (CPS ≥ 10), the 12-month overall survival rate was 43% in the pembrolizumab group versus only 20% in the chemotherapy group, representing a 31% reduction in the risk of death.
Nivolumab (Opdivo): The ATTRACTION-3 study confirmed that nivolumab demonstrated significantly superior overall survival compared with chemotherapy in PD-1 non-selective, unresectable advanced or recurrent esophageal cancer.
Tislelizumab: In March 2025, the U.S. FDA approved tislelizumab in combination with platinum-containing chemotherapy as first-line treatment for unresectable or metastatic esophageal squamous cell carcinoma with PD-L1 expression ≥ 1%. The NCCN Guidelines (2025 V3) have designated the tislelizumab regimen as a preferred first-line therapy.
Updates to domestic guidelines: The 2025 CSCO Guidelines for the Diagnosis and Treatment of Esophageal Cancer clearly recommend PD-1 inhibitors in combination with chemotherapy as a Grade I recommendation for patients with PD-L1-positive expression (CPS ≥ 1), while downgrading to Grade II recommendation for those with PD-L1 < 1. In the neoadjuvant setting, the addition of camrelizumab plus chemotherapy has been newly included as a Grade II recommendation.
Survival improvement in advanced-stage patients: Under conventional chemotherapy, the 5-year survival rate for advanced esophageal cancer is less than 5%, with a 3-year survival rate of only 12.8%. In contrast, immunotherapy enables approximately 25% of patients to survive beyond 3 years, effectively doubling the survival outcome.
III. Palliative Care for Malignant Dysphagia. For patients who are not amenable to curative treatment, relieving dysphagia and improving quality of life are of paramount importance:
Esophageal stents (SEMS): Placement is relatively straightforward, and relief of dysphagia is often immediate. However, attention should be paid to complications including pain (incidence up to 60%), bleeding, and migration (incidence up to 40%).
External beam radiotherapy (EBRT): Over 75% of patients experience symptomatic improvement, with relatively durable efficacy.
Endoscopic tissue ablation (laser, argon plasma coagulation, photodynamic therapy, etc.): Can improve swallowing symptoms but has relatively limited application.
Traditional Chinese Medicine (TCM): As an adjunctive therapy, it can regulate vital energy and blood circulation, enhance immune function, and alleviate discomfort from radiotherapy and chemotherapy. It is particularly beneficial for frail and elderly patients.