Oesophageal cancer

Introduction
Oesophageal cancer is a malignant tumour arising from the epithelial lining of the oesophagus. It is a highly aggressive cancer with a poor overall prognosis due to late-stage presentation in most patients. Two main histological types exist:

• Squamous cell carcinoma (SCC) – Originates from squamous epithelium; more common in the upper and middle thirds of the oesophagus.

• Adenocarcinoma – Originates from glandular epithelium, typically in the lower third of the oesophagus, often arising from Barrett’s oesophagus.

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Epidemiology

• Eighth most common cancer worldwide and sixth leading cause of cancer-related death.

• SCC predominates in Asia and Africa; adenocarcinoma is more common in Western countries.

• More common in men (male-to-female ratio approximately 3:1).

• Peak incidence: 50–70 years of age.

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Risk Factors

For Squamous Cell Carcinoma:

• Tobacco smoking.

• Alcohol consumption.

• Dietary deficiencies (low intake of fruits and vegetables).

• Consumption of very hot beverages.

• History of head and neck cancers.

• Achalasia.

• Plummer–Vinson syndrome.

For Adenocarcinoma:

• Chronic gastro-oesophageal reflux disease (GERD).

• Barrett’s oesophagus.

• Obesity.

• Smoking.

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Pathophysiology

• Chronic irritation or inflammation leads to dysplasia, followed by carcinoma in situ, and eventually invasive carcinoma.

• In adenocarcinoma, prolonged acid exposure induces metaplasia (Barrett’s oesophagus), transforming squamous epithelium into columnar epithelium, which is prone to malignant change.

• Tumours infiltrate locally and often spread early to regional lymph nodes due to rich lymphatic drainage in the oesophagus.

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Clinical Features

Early stages: Often asymptomatic.

Progressive disease:

• Dysphagia (initially to solids, later to liquids).

• Odynophagia (painful swallowing).

• Unintentional weight loss.

• Retro-sternal discomfort or pain.

• Hoarseness (recurrent laryngeal nerve involvement).

• Cough, aspiration, or pneumonia (tracheo-oesophageal fistula).

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Diagnosis

1. History and examination – Focus on progressive dysphagia, weight loss, risk factors.

2. Investigations:

• Upper gastrointestinal endoscopy: Direct visualization and biopsy for histological confirmation.

• Endoscopic ultrasound (EUS): Staging of tumour depth and local lymph node involvement.

• CT scan (chest and abdomen): Assess local invasion, nodal involvement, and metastases.

• PET-CT: Detects distant metastases.

• Barium swallow: May show irregular narrowing or “apple-core” lesion.

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Staging (TNM classification)

• T: Depth of tumour invasion.

• N: Regional lymph node involvement.

• M: Presence of distant metastases.

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Management

Goals:

• Cure in localized disease.

• Palliation in advanced disease to improve swallowing and quality of life.

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1. Surgical Management – Mainstay for localized resectable disease:

• Oesophagectomy (transhiatal or transthoracic approach) with gastric pull-up or colonic interposition.

• Requires adequate cardiopulmonary reserve.

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2. Neoadjuvant and Adjuvant Therapy:

• Neoadjuvant chemoradiotherapy before surgery for locally advanced disease improves survival (e.g., combination of cisplatin and 5-fluorouracil with radiotherapy).

• Adjuvant therapy in selected cases after surgery.

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3. Definitive Chemoradiotherapy – For non-surgical candidates or unresectable tumours:

• Cisplatin + 5-fluorouracil (5-FU) regimen with concurrent radiotherapy.

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4. Palliative Management – For advanced or metastatic disease:

a. Symptom relief:

• Endoscopic stenting (self-expanding metal stents) to relieve dysphagia.

• Palliative radiotherapy or brachytherapy.

• Nutritional support via feeding gastrostomy or jejunostomy if needed.

b. Palliative chemotherapy:

• Cisplatin + 5-FU.

• Carboplatin + paclitaxel.

• FOLFOX regimen (oxaliplatin, leucovorin, 5-FU).

c. Targeted therapy:

• Trastuzumab for HER2-positive adenocarcinoma: loading dose 8 mg/kg IV, then 6 mg/kg every 3 weeks.

• Nivolumab or pembrolizumab (immune checkpoint inhibitors) for PD-L1-positive or refractory cases.

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Common Chemotherapy Doses (adult standard):

• Cisplatin: 75 mg/m² IV on day 1 of a 3–4 week cycle.

• 5-FU: 1000 mg/m²/day IV continuous infusion for 4–5 days.

• Paclitaxel: 175 mg/m² IV over 3 hours every 3 weeks.

• Carboplatin: AUC 5–6 IV every 3 weeks.

• Oxaliplatin: 85 mg/m² IV every 2 weeks in FOLFOX regimen.

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Prognosis

• Five-year survival rate is <20% overall due to late-stage diagnosis.

• Prognosis is best in early-stage tumours treated surgically.

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Complications

• Local invasion to trachea, lungs, or aorta.

• Metastases to liver, lungs, bones.

• Malnutrition.

• Tracheo-oesophageal fistula.