Esophageal cancer is a malignant tumour arising from the epithelial lining of the oesophagus, the muscular tube that transports food from the pharynx to the stomach. It is an aggressive malignancy associated with late presentation, rapid progression, and poor overall survival.

Histologically, esophageal cancer is classified mainly into two major types:

1. Squamous cell carcinoma (SCC)

   • Arises from the squamous epithelium of the oesophagus.

   • Historically the most common type worldwide.

   • Strongly associated with tobacco and alcohol exposure.

2. Adenocarcinoma

   • Arises from glandular epithelial cells, usually in the distal oesophagus.

   • Associated with chronic gastroesophageal reflux disease (GERD), Barrett’s oesophagus, and obesity.

Most patients present at advanced stages because early disease is often asymptomatic. Dysphagia is the most common presenting symptom and is frequently associated with weight loss, malnutrition, and poor performance status.

Treatment depends on tumour stage, location, histological type, and patient fitness. Management includes surgery, radiotherapy, chemotherapy, nutritional support, and palliative interventions for advanced disease.

Epidemiology

Esophageal cancer is among the leading causes of cancer-related mortality worldwide due to its aggressive nature and late diagnosis.

• It occurs more commonly in males than females.

• Incidence varies geographically depending on risk factors.

• Squamous cell carcinoma predominates in many African and Asian countries.

• Adenocarcinoma is more common in Western countries.

In Tanzania and other East African countries, esophageal cancer represents an important cancer burden and commonly presents with advanced disease requiring multidisciplinary oncological management.

Risk factors

Risk factors differ according to histological subtype.

Risk factors for squamous cell carcinoma

Tobacco use

• Cigarette smoking.

• Other forms of tobacco exposure.

Alcohol consumption

• Chronic heavy alcohol intake significantly increases risk.

Dietary factors

• Low intake of fruits and vegetables.

• Consumption of very hot beverages.

• Nutritional deficiencies.

Medical conditions

• Achalasia.

• Esophageal strictures.

• Caustic ingestion injury.

• Plummer–Vinson syndrome.

Other factors

• Increasing age.

• Male sex.

• Family history of esophageal cancer.

Risk factors for adenocarcinoma

Gastroesophageal reflux disease (GERD)

Chronic acid reflux causes repeated injury to the lower oesophageal mucosa.

Barrett’s oesophagus

• Metaplastic transformation of normal squamous epithelium into columnar epithelium.

• Considered a premalignant condition for adenocarcinoma.

Obesity

• Particularly central obesity, which increases reflux risk.

Other factors

• Increasing age.

• Male sex.

• Smoking.

• Family history.

Pathophysiology

Esophageal cancer develops through progressive genetic and cellular changes leading to uncontrolled cellular proliferation, invasion, and metastasis.

Squamous cell carcinoma

Chronic mucosal irritation from tobacco, alcohol, and other environmental factors causes:

1. Inflammation and epithelial injury.

2. Dysplastic changes.

3. Carcinoma development.

Tumours commonly arise in the middle and upper thirds of the oesophagus.

Adenocarcinoma

The pathway usually involves:

1. Chronic gastroesophageal reflux.

2. Development of Barrett’s oesophagus.

3. Intestinal metaplasia.

4. Dysplasia.

5. Adenocarcinoma.

Adenocarcinomas commonly arise in the distal oesophagus and gastroesophageal junction.

Spread of disease

Esophageal cancer spreads through:

• Direct local invasion into surrounding structures.

• Lymphatic spread to regional lymph nodes.

• Hematogenous spread to:

  • Liver.

  • Lungs.

  • Bone.

Clinical presentation

Clinical manifestations depend on tumour size, location, stage, and presence of metastases.

Early disease may be asymptomatic or present with mild swallowing difficulty. Progressive obstruction occurs as the tumour enlarges.

Most patients present with advanced disease associated with nutritional decline and reduced functional status.

Symptoms

Common symptoms

Dysphagia

• The most common presenting symptom.

• Initially affects solid foods.

• Progresses to difficulty swallowing liquids as obstruction worsens.

Weight loss

• Due to reduced oral intake and cancer-related metabolic changes.

• Often associated with poor prognosis.

Retrosternal chest discomfort

• Pain or discomfort behind the sternum.

• May worsen during swallowing.

Odynophagia

• Painful swallowing due to mucosal ulceration.

Regurgitation

• Backflow of food due to obstruction.

Gastrointestinal symptoms

• Nausea.

• Vomiting.

• Early satiety.

Symptoms due to advanced disease

• Persistent cough.

• Hoarseness of voice due to recurrent laryngeal nerve involvement.

• Shortness of breath.

• Bone pain due to skeletal metastases.

• Abdominal pain due to liver metastases.

Clinical signs

Clinical findings may include:

General signs

• Weight loss.

• Cachexia.

• Poor nutritional status.

• Dehydration.

Signs of local disease

• Difficulty swallowing.

• Cervical lymphadenopathy.

• Hoarse voice.

• Signs of aspiration.

Signs of metastatic disease

• Hepatomegaly due to liver metastases.

• Respiratory findings due to lung involvement.

• Bone tenderness or pathological fractures.

Differential diagnosis

Differential diagnoses of esophageal cancer include:

• Benign esophageal stricture.

• Gastroesophageal reflux disease.

• Achalasia.

• Esophageal motility disorders.

• Esophageal candidiasis.

• Esophageal tuberculosis.

• Esophageal lymphoma.

• External compression of the oesophagus.

• Esophageal webs or rings.

Diagnostic criteria

Diagnosis is suspected in patients presenting with:

• Progressive dysphagia.

• Dysphagia associated with weight loss.

• Poor nutritional status.

• Persistent upper gastrointestinal symptoms.

• Risk factors for esophageal malignancy.

Definitive diagnosis requires:

• Endoscopic visualization of the lesion.

• Biopsy demonstrating malignant histology.

Investigations

Laboratory investigations

Baseline investigations include:

Full blood count (FBC)

To assess:

• Anaemia.

• Infection.

• General health status.

Liver function tests (LFTs)

To assess:

• Liver involvement.

• Baseline chemotherapy suitability.

Renal function tests

• Urea.

• Creatinine.

Important before chemotherapy, especially cisplatin-based regimens.

Imaging investigations

Barium swallow and meal

Useful for:

• Identifying oesophageal obstruction.

• Assessing tumour location and length.

• Evaluating swallowing difficulty.

CT scan of chest and abdomen

Used for staging:

• Primary tumour assessment.

• Regional lymph node involvement.

• Distant metastases.

Abdominal ultrasound scan

Used mainly for:

• Detection of liver metastases.

• Assessment of abdominal disease.

Endoscopic investigations

Oesophagogastroduodenoscopy (OGD)

or

Rigid oesophagoscopy

Allows:

• Direct visualization of tumour.

• Assessment of lesion characteristics.

• Biopsy collection.

Histopathology

Confirms:

• Squamous cell carcinoma.

• Adenocarcinoma.

• Tumour differentiation and characteristics.

Staging

Esophageal cancer is staged using the TNM staging system:

T – Primary tumour

Determined by:

• Depth of invasion into oesophageal wall.

• Extension into adjacent structures.

N – Regional lymph nodes

Determined by:

• Number and location of involved lymph nodes.

M – Distant metastases

Assessment of spread to:

• Liver.

• Lung.

• Bone.

• Other distant organs.

Staging guides treatment selection and prognosis.

Management

Management should be individualized according to:

• Tumour stage.

• Histological subtype.

• Tumour location.

• Patient performance status.

• Nutritional status.

Management involves:

1. Initial assessment and nutritional optimization.

2. Staging and multidisciplinary treatment planning.

3. Definitive treatment where possible.

4. Palliative care for advanced disease.

Non-pharmacological treatment

Nutritional support

Malnutrition is common due to dysphagia.

Management includes:

Oral nutritional support

• Dietary modification.

• High-calorie nutritional supplements where tolerated.

Enteral feeding

Indicated when oral intake is inadequate.

Options include:

• Feeding gastrostomy tube.

• Esophageal stenting for obstruction relief.

Parenteral nutrition

Used when:

• Severe obstruction prevents enteral feeding.

• Adequate nutrition cannot be achieved through gastrointestinal feeding.

Surgery

Surgery is the main curative treatment for resectable disease.

Common procedures include:

• Esophagectomy with reconstruction.

• Regional lymph node dissection.

Surgery is considered in:

• Early-stage disease.

• Selected locally advanced disease following neoadjuvant therapy.

Pharmacological treatment

Chemotherapy

Chemotherapy is used in:

• Neoadjuvant setting.

• Adjuvant setting.

• Palliative treatment.

Neoadjuvant chemotherapy

Used before surgery to reduce tumour burden and improve surgical outcomes.

Regimen 1

Paclitaxel – 175 mg/m² – intravenous infusion over 3 hours – day 1ANDCisplatin – 75 mg/m² – intravenous infusion over 1 hour – day 1

Frequency:

• Every 21 days.

Duration:

• Up to 6 cycles.

Alternative regimen

Paclitaxel – 175 mg/m² – intravenous infusion over 3 hours – day 1ANDCarboplatin – AUC 5 – intravenous infusion over 1 hour – day 1

Frequency:

• Every 21 days.

Duration:

• Up to 6 cycles.

Alternative regimen

Docetaxel – 75 mg/m² – intravenous infusion over 3 hours – day 1ANDCisplatin – 75 mg/m² – intravenous infusion over 1 hour – day 1

Frequency:

• Every 21 days.

Duration:

• Up to 6 cycles.

Adjuvant chemotherapy

Recommended regimen:

5-Fluorouracil (5-FU) – 1000 mg/m² – intravenous bolus – day 1 to day 5ANDCisplatin – 75 mg/m² – intravenous infusion over 1 hour – day 1

Frequency:

• Every 21 days.

Duration:

• Up to 6 cycles.

Palliative chemotherapy

Used for unresectable disease or metastatic disease.

Recommended regimen:

Capecitabine – 1000 mg/m² – oral – every 12 hours – day 1 to day 14

Frequency:

• Every 21-day cycle.

Duration:

• Up to 6 cycles or until:

  • Disease progression.

  • Unacceptable toxicity.

Radiotherapy

Radiotherapy may be used as:

Definitive therapy

• For selected early-stage patients unable to undergo surgery.

• Often combined with chemotherapy.

Neoadjuvant therapy

• Before surgery to improve tumour control.

Adjuvant therapy

• After surgery in selected patients.

Palliative therapy

Used for:

• Relief of dysphagia.

• Pain control.

• Bleeding control.

Management according to underlying cause

Squamous cell carcinoma

Management depends on stage:

• Early disease:

  • Surgical resection.

  • Definitive chemoradiotherapy when appropriate.

• Advanced disease:

  • Systemic chemotherapy.

  • Palliative radiotherapy.

  • Symptom control.

Adenocarcinoma

Management includes:

• Surgical resection for resectable disease.

• Neoadjuvant chemotherapy/chemoradiotherapy for locally advanced disease.

• Systemic therapy for metastatic disease.

Obstructive disease with complete dysphagia

Management includes:

• Esophageal stenting.

• Gastrostomy tube placement.

• Nutritional support.

• Palliative radiotherapy where appropriate.

Referral

All patients with suspected or confirmed esophageal cancer should be referred to specialized cancer centres for multidisciplinary management.

Referral should involve:

• Surgical oncology.

• Medical oncology.

• Radiation oncology.

• Gastroenterology.

• Nutrition specialists.

Urgent referral indications

• Progressive dysphagia.

• Complete inability to swallow.

• Airway compromise.

• Significant weight loss.

• Suspected metastatic disease.

• Severe malnutrition.

Complications

Disease-related complications

• Complete esophageal obstruction.

• Severe malnutrition.

• Dehydration.

• Aspiration pneumonia.

• Tracheoesophageal fistula.

• Gastrointestinal bleeding.

• Metastatic disease.

Treatment-related complications

Surgery

• Anastomotic leakage.

• Infection.

• Respiratory complications.

• Nutritional problems.

Chemotherapy

• Neutropenia.

• Anaemia.

• Nausea and vomiting.

• Renal toxicity (cisplatin).

• Peripheral neuropathy.

Radiotherapy

• Esophagitis.

• Fatigue.

• Tissue fibrosis.

Prognosis

Esophageal cancer generally has a poor prognosis because most patients present with advanced disease.

Prognosis depends on:

• Stage at diagnosis.

• Tumour histology.

• Response to treatment.

• Nutritional status.

• Performance status.

Patients diagnosed at early stages who undergo curative treatment have better outcomes compared with those presenting with metastatic disease.

Prevention

Preventive strategies include:

• Avoid tobacco use.

• Reduce harmful alcohol consumption.

• Maintain healthy body weight.

• Early diagnosis and treatment of GERD.

• Surveillance of high-risk patients with Barrett’s oesophagus.

• Healthy diet rich in fruits and vegetables.

• Early evaluation of persistent dysphagia.