Oesophageal Adenocarcinoma

Oesophageal adenocarcinoma arises from glandular epithelium, usually in the distal oesophagus, and is strongly associated with Barrett oesophagus, chronic gastroesophageal reflux, central obesity, smoking and male sex.

It spreads through the rich submucosal lymphatic network, so nodal disease may occur before the primary tumour becomes bulky. Management is determined by depth of invasion, nodal status, distant metastases, physiological fitness and whether an R0 resection is achievable.

Superficial mucosal disease can often be treated endoscopically. Locally advanced resectable disease requires multimodality treatment. Metastatic disease is managed primarily with systemic therapy.

Progressive dysphagia is typical, initially to solids and later liquids.

Other important features are:

• Progressive weight loss
• Regurgitation
• Odynophagia
• Retrosternal discomfort
• Iron deficiency anaemia
• Aspiration or recurrent respiratory infection

Hoarseness suggests recurrent laryngeal nerve involvement. Persistent cough associated with swallowing raises concern for airway invasion or fistulation.

Upper gastrointestinal endoscopy with multiple biopsies: establishes adenocarcinoma and defines tumour level.

CT chest, abdomen and pelvis plus FDG PET CT: establish metastatic burden and resectability.

Endoscopic ultrasound: refines local T stage and regional nodal disease when curative treatment remains possible.

Early tumours require careful pathological assessment of depth, differentiation, lymphovascular invasion and resection margins because these determine whether endoscopic treatment is adequate.

Early disease

Selected T1a intramucosal adenocarcinoma can undergo endoscopic mucosal resection or endoscopic submucosal dissection, followed by eradication of residual dysplastic Barrett mucosa where present.

Submucosal invasion substantially increases nodal metastasis risk. Fit patients with T1b disease, poor differentiation, lymphovascular invasion or other high risk features generally require oesophagectomy with regional lymphadenectomy.

Resectable locally advanced disease

For fit patients with resectable adenocarcinoma, particularly clinical T2 or greater or node positive disease, perioperative FLOT is now a major preferred approach. Contemporary randomized evidence demonstrated better survival than preoperative CROSS chemoradiotherapy in resectable oesophageal adenocarcinoma.

A standard FLOT cycle is given every 14 days:

• Docetaxel 50 mg/m² IV day 1
• Oxaliplatin 85 mg/m² IV day 1
• Leucovorin 200 mg/m² IV day 1
• Fluorouracil 2600 mg/m² continuous IV infusion over 24 hours

Give four cycles before surgery and four cycles after recovery when tolerated.

Preoperative chemoradiotherapy remains appropriate in selected patients, particularly where local tumour control or surgical considerations favour it.

A standard CROSS regimen is:

• Paclitaxel 50 mg/m² IV weekly
• Carboplatin AUC 2 IV weekly

for five weeks with radiotherapy 41.4 Gy in 23 fractions, followed by oesophagectomy.

For residual pathological disease after neoadjuvant chemoradiotherapy and complete resection, adjuvant immune checkpoint therapy may be appropriate according to tumour stage, previous treatment and oncology assessment.

Surgery

Distal oesophageal adenocarcinoma is commonly treated with Ivor Lewis oesophagectomy, combining abdominal gastric conduit formation with transthoracic oesophageal resection and intrathoracic anastomosis.

The oncological objectives are:

• R0 resection
• Adequate proximal and distal margins
• Regional lymphadenectomy
• Preservation of a well perfused gastric conduit

Major postoperative complications include anastomotic leak, conduit ischaemia, pneumonia, atrial arrhythmia, recurrent laryngeal nerve injury and chyle leak.

Persistent postoperative tachycardia, respiratory deterioration, fever or unexplained sepsis should trigger immediate assessment for anastomotic or conduit complications.

Metastatic disease

Test advanced adenocarcinoma for HER2, PD L1, MSI or mismatch repair deficiency and other actionable biomarkers because these directly alter systemic treatment.

Malignant dysphagia can be palliated rapidly with a self expanding metal stent. Radiotherapy provides slower but often more durable dysphagia control in patients with a longer expected survival.