Esophageal Cancer

The esophagus is a muscular tube that carries food and liquids from the throat to the stomach. Esophageal cancer usually begins in the inner lining of the esophagus and can grow outward through deeper layers and into surrounding tissues.

The two main types are squamous cell carcinoma and adenocarcinoma. Squamous cell carcinoma arises from the flat cells lining the esophagus and can occur anywhere along the organ. Adenocarcinoma develops from glandular cells and most commonly occurs in the lower esophagus near the gastroesophageal junction.

These two types differ in their risk factors and, in some settings, in their perioperative and systemic treatment strategies. Histology is therefore an important part of treatment planning.

Esophageal cancer usually develops through the interaction of multiple factors over time, and risk factors differ between squamous cell carcinoma and adenocarcinoma.

Important risk factors for esophageal squamous cell carcinoma include smoking, heavy alcohol use, repeated consumption of very hot beverages or foods, certain dietary factors, achalasia, and some other conditions involving chronic injury to the esophagus.

For esophageal adenocarcinoma, important risk factors include gastroesophageal reflux disease, Barrett’s esophagus, obesity, smoking, and increasing age.

Barrett’s esophagus occurs when the normal lining of the lower esophagus changes after long-term exposure to reflux. It increases the risk of adenocarcinoma, although most people with Barrett’s esophagus never develop cancer.

Early esophageal cancer may cause no noticeable symptoms. Some early tumors are found during endoscopy or screening of people at increased risk.

As the tumor begins to narrow the esophagus, possible symptoms include:

• A sensation that food is getting stuck

• Progressively worsening difficulty swallowing

• Pain with swallowing

• Discomfort or pain behind the breastbone

• Loss of appetite

• Unexplained weight loss

• Hoarseness

• Persistent cough

Progressive dysphagia often begins with difficulty swallowing solid foods and may later affect softer foods and liquids, although symptoms do not always follow the same pattern in every patient.

Advanced local disease may also cause persistent chest or back pain, hoarseness, or communication between the esophagus and airway, which can lead to coughing while eating or drinking and recurrent respiratory infections.

Endoscopy with biopsy is central to the diagnosis of esophageal cancer.

Endoscopy allows direct visualization of the tumor and collection of tissue for pathologic examination. Pathology confirms the diagnosis and determines whether the tumor is squamous cell carcinoma, adenocarcinoma, or another type.

After diagnosis, staging commonly includes contrast-enhanced CT of the chest and abdomen, PET/CT in appropriate patients, and endoscopic ultrasound for selected localized tumors. NCI identifies endoscopic ultrasound, CT, and PET/CT as major staging tools for esophageal cancer.

A barium swallow may still be useful in selected situations but is no longer the central test for diagnosing early esophageal cancer.

Staging

Esophageal cancer is primarily staged using the AJCC TNM system.

T describes how deeply the primary tumor has grown into the esophageal wall or nearby tissues. N describes regional lymph node involvement. M indicates whether the cancer has spread to distant parts of the body.

For treatment planning, it is also important to know whether the tumor is confined to the superficial layers, whether regional lymph nodes are involved, whether complete surgical resection is feasible, and whether distant metastases are present.

Early Esophageal Cancer

Selected very early esophageal cancers that are limited to the superficial layers and have a low risk of lymph node spread may be removed endoscopically rather than by removing the esophagus.

Techniques include endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR).

After endoscopic removal, pathology is used to assess depth of invasion, differentiation, surgical margins, and lymphovascular invasion. Additional surgery or chemoradiation may be recommended if higher-risk features are found.

Resectable Locally Advanced Esophageal Cancer

For resectable cancers that extend beyond the earliest stages, treatment often involves therapy before or around the time of surgery rather than surgery alone.

For locally advanced resectable esophageal squamous cell carcinoma, neoadjuvant chemoradiation followed by esophagectomy remains an important standard strategy.

For locally advanced resectable adenocarcinoma of the lower esophagus or gastroesophageal junction, perioperative chemotherapy has become a preferred strategy for many patients according to the 2025 ESMO guideline update.

Definitive Concurrent Chemoradiotherapy

Surgery is not required for every patient with localized esophageal cancer.

Definitive concurrent chemoradiation can be used for selected squamous cell carcinomas, particularly cervical esophageal cancers, unresectable tumors, patients who are not suitable for surgery, or situations in which organ preservation is preferred.

Close surveillance is needed afterward, and salvage surgery may be considered for selected patients with resectable persistent or recurrent disease.

Surgery

Esophagectomy is an important component of multimodality treatment for many patients with resectable esophageal cancer.

Surgery generally involves removing the affected portion of the esophagus and regional lymph nodes, followed by reconstruction of the digestive tract, often using the stomach.

Open, minimally invasive, and robot-assisted approaches may be considered depending on tumor location, the patient’s condition, and surgical expertise.

Postoperative Adjuvant Immunotherapy

Adjuvant immunotherapy is now an important treatment consideration for selected patients.

Patients with esophageal or gastroesophageal junction cancer who receive neoadjuvant chemoradiation followed by complete surgical resection but still have residual pathologic disease may be candidates for adjuvant nivolumab.

This approach was established by the CheckMate 577 trial and is now incorporated into modern treatment pathways.

Advanced or Metastatic Esophageal Cancer

Treatment for advanced esophageal cancer is no longer limited to chemotherapy alone.

Systemic therapy is the main treatment for unresectable metastatic disease.

For esophageal squamous cell carcinoma, immune checkpoint inhibitors combined with chemotherapy have improved outcomes and are now widely incorporated into first-line treatment. The specific regimen depends on factors such as PD-L1 expression, previous treatment, overall health, and local drug approvals.

For advanced esophageal adenocarcinoma, biomarker testing may include HER2, PD-L1, and MSI/MMR. These results can help identify patients who may benefit from HER2-targeted therapy or immunotherapy.

Esophageal Stents and Nutritional Support

Esophageal stents are mainly used to relieve severe dysphagia caused by tumor-related narrowing of the esophagus. Self-expanding metal stents are an established palliative option for dysphagia in advanced esophageal cancer.

However, a stent is not automatically the first choice for every patient with swallowing difficulty, particularly when curative chemoradiation or surgery is planned.

Nutritional support is important throughout treatment and may include dietary modification, oral nutritional supplements, tube feeding, or other approaches depending on the patient’s needs.