Key Facts

Oesophageal cancer has a poor prognosis overall due to late presentation, but outcomes for operable disease have improved with modern neoadjuvant regimens.

Epidemiology

• ~9,300 new cases/year in the UK; ~7,900 deaths/year
• Male:female ratio 3:1 (adenocarcinoma); SCC more equal
• Adenocarcinoma incidence rising rapidly (now >50% of oesophageal cancers in the UK)
• Squamous cell carcinoma incidence declining (linked to reduced smoking)

Aetiology

• Adenocarcinoma: Barrett's oesophagus (10× risk), GORD, obesity, smoking
• SCC: smoking, alcohol (synergistic), hot drinks, caustic injury, Plummer-Vinson syndrome, achalasia, tylosis

Pathophysiology

• Barrett's → dysplasia → adenocarcinoma: GORD causes chronic oesophagitis → columnar metaplasia (Barrett's) → low-grade dysplasia → high-grade dysplasia → invasive adenocarcinoma
• SCC: squamous epithelium → dysplasia → carcinoma in situ → invasive carcinoma
• Oesophagus lacks serosa → early transmural spread and lymph node involvement
• Lymphatic drainage is longitudinal → skip metastases common

Typical Symptoms

• Progressive dysphagia: initially solids, then liquids (by the time dysphagia occurs, >50% of lumen is occluded)
• Weight loss (often >10%)
• Odynophagia (painful swallowing)
• Regurgitation
• Chest pain or epigastric pain
• Iron deficiency anaemia

Advanced Disease

• Hoarseness (recurrent laryngeal nerve involvement)
• Persistent cough or aspiration pneumonia (tracheo-oesophageal fistula)
• Hepatomegaly (liver metastases)
• Supraclavicular lymphadenopathy (Virchow's node — left)

Red Flags

• Progressive dysphagia (any age — urgent OGD)
• Unintentional weight loss >3kg
• Iron deficiency anaemia without obvious cause
• Dysphagia + weight loss + age ≥55
• New dyspepsia in patients ≥55 with alarm symptoms

Bedside

• BMI, nutritional assessment
• Abdominal examination (hepatomegaly, ascites)
• Cervical lymph node palpation (Virchow's)

Bloods

• FBC (anaemia), U&Es, LFTs, albumin (nutritional status)
• CEA (monitoring, not diagnostic)

Imaging

• OGD with biopsy: gold standard diagnostic investigation
• CT chest/abdomen/pelvis: TNM staging
• EUS (endoscopic ultrasound): T and N staging (depth of invasion)
• PET-CT: detects distant metastases, guides treatment decisions
• Staging laparoscopy: for GOJ tumours (peritoneal disease)

Special Tests

• Histopathology: SCC vs adenocarcinoma, differentiation grade
• HER2 testing: for GOJ adenocarcinoma (trastuzumab if HER2+, ToGA trial)
• PD-L1 CPS: guides immunotherapy use
• Nutritional assessment and dietitian review
• Swallowing assessment

Non-pharmacological

• MDT discussion mandatory (upper GI surgeon, oncologist, CNS, dietitian, SALT)
• Nutritional optimisation (supplementary feeds, consider feeding jejunostomy)
• Smoking and alcohol cessation
• Psychological support

Pharmacological

• Operable adenocarcinoma: perioperative FLOT (5-FU, leucovorin, oxaliplatin, docetaxel) × 4 pre-op + 4 post-op (FLOT4 trial)
• Operable SCC: neoadjuvant CROSS regimen (carboplatin + paclitaxel + 41.4Gy RT) then surgery (CROSS trial)
• Inoperable locally advanced: definitive chemoradiotherapy (cisplatin + 5-FU + 50Gy)
• Metastatic adenocarcinoma: platinum + fluoropyrimidine ± trastuzumab if HER2+ (ToGA); nivolumab + chemo if PD-L1 CPS ≥5 (CheckMate-649)
• Metastatic SCC: platinum + 5-FU + pembrolizumab if PD-L1 CPS ≥10 (KEYNOTE-590)
• Adjuvant: nivolumab after neoadjuvant chemoRT if residual disease (CheckMate-577)

Surgical/Interventional

• Ivor Lewis oesophagectomy: right thoracotomy + laparotomy (mid/lower oesophagus)
• McKeown (3-stage) oesophagectomy: includes cervical anastomosis (upper oesophagus)
• Minimally invasive oesophagectomy: laparoscopic/thoracoscopic (reducing morbidity)
• Endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD): for T1a (intramucosal) adenocarcinoma or high-grade dysplasia in Barrett's
• Radiofrequency ablation (RFA): for Barrett's with dysplasia (after EMR of visible lesions)
• Palliative stenting: for dysphagia in inoperable disease (self-expanding metal stent)
• Palliative RT: for dysphagia, bleeding

Referral Criteria

• Dysphagia at any age: urgent 2-week wait OGD
• Age ≥55 with unexplained weight loss and upper GI symptoms: 2-week wait
• All confirmed oesophageal cancers: upper GI cancer MDT

• Stage I: 5-year survival 60-80%
• Stage II-III (operable): 5-year survival 35-45% with neoadjuvant + surgery
• Stage IV (metastatic): median survival 8-12 months
• Overall 5-year survival: approximately 15-20%
• FLOT4 (adenocarcinoma): median OS 50 months with perioperative FLOT
• CROSS (SCC): 5-year OS 47% with neoadjuvant chemoRT + surgery
• Barrett's surveillance: early detection of dysplasia/cancer improves outcomes
• Operative mortality for oesophagectomy: 2-5% in high-volume centres

Barrett's Oesophagus Surveillance (BSG 2014)

Key Trials in Oesophageal Cancer