Oesophageal cancer

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Oesophageal cancer most commonly comprises squamous-cell carcinoma and adenocarcinoma. Progressive mechanical dysphagia typically evolves from solids to liquids, but early disease may cause only odynophagia, retrosternal discomfort or iron-deficiency anaemia. Rapid weight loss reflects obstruction and systemic catabolism. Hoarseness suggests recurrent-laryngeal involvement; cough with swallowing raises fistula or aspiration. New dysphagia is an investigation trigger even when reflux is longstanding.

Endoscopy visualises level, length and tightness and obtains multiple biopsies. CT maps tumour, nodes and distant disease. PET-CT detects otherwise occult metastasis and guides radical fields, while EUS gives high-resolution wall-layer and regional-node assessment when the lumen can be traversed and curative staging remains relevant. No single scan is perfectly specific: a solitary metastasis or decisive node may need tissue before abandoning curative intent.

Curative treatment is histology and level specific. Very early mucosal adenocarcinoma or squamous neoplasia can be removed endoscopically. Locally advanced operable adenocarcinoma may receive perioperative combination chemotherapy or neoadjuvant chemoradiation followed by oesophagectomy. Definitive chemoradiotherapy is central for cervical and many thoracic squamous cancers and for patients unfit for surgery. Prehabilitation, cardiopulmonary testing and nutrition are essential because oesophagectomy has major respiratory, anastomotic and functional burden.

Metastatic or unresectable treatment combines biomarker-directed systemic therapy with dysphagia control. HER2, PD-L1 and mismatch-repair status influence adenocarcinoma treatment, while PD-L1 and histology guide squamous options. Stents restore swallowing within days but can cause pain, reflux, migration and fistula; radiation works more slowly. Feeding access should support the agreed treatment without compromising the gastric conduit or increasing aspiration.

Key points

Progressive dysphagia and weight loss is oesophageal cancer until promptly investigated; urgent upper-GI endoscopy with multiple biopsies is the first diagnostic route.
Adenocarcinoma usually affects distal oesophagus or gastro-oesophageal junction and is associated with Barrett reflux and obesity; squamous cancer more often affects upper or mid oesophagus and tobacco–alcohol exposure.
The diagnostic reference standard is histology from endoscopic biopsy; repeat with deeper or image-guided sampling when visible or radiological suspicion remains despite non-diagnostic tissue.
After diagnosis, contrast CT chest and abdomen is the first staging overview, followed by PET-CT and endoscopic ultrasound when curative treatment remains plausible and each test will change management.
Use bronchoscopy for an upper or mid-oesophageal tumour abutting the tracheobronchial tree and staging laparoscopy for selected junctional or gastric-side adenocarcinoma at peritoneal risk.
Early mucosal neoplasia may be treated by endoscopic resection with eradication of remaining Barrett dysplasia, preserving the oesophagus.
Resectable adenocarcinoma commonly receives perioperative chemotherapy or neoadjuvant chemoradiation before oesophagectomy; anatomy, fitness and current MDT protocol determine the sequence.
Squamous cancer is often treated with definitive chemoradiotherapy, particularly cervically or when surgery would be highly morbid, with salvage surgery reserved for selected persistent or recurrent disease.
Advanced systemic treatment depends on squamous versus adenocarcinoma histology and HER2, PD-L1 and mismatch-repair or microsatellite status where relevant.
Nutrition is assessed at diagnosis. Use oral adaptation, dietetic supplements, enteral access or parenteral support according to obstruction, aspiration, treatment intent and anatomy.
For non-curative dysphagia, self-expanding metal stent gives rapid relief, whereas radiotherapy or brachytherapy may provide slower but more durable relief in a patient likely to live longer.
Do not place a stent reflexively before curative surgery or chemoradiation; migration, perforation and interference with later treatment can outweigh short-term benefit.
Palliative care addresses dysphagia, pain, saliva, aspiration, bleeding and family distress alongside active systemic or radiation treatment.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Reflux and Barrett metaplasia

Chronic gastro-oesophageal reflux, central obesity and Barrett intestinal metaplasia increase distal oesophageal and junctional adenocarcinoma risk through inflammation and dysplasia.

Tobacco and alcohol

Smoking increases both principal histologies, while heavy alcohol acts strongly with tobacco to drive squamous-cell carcinoma, particularly in upper and middle oesophagus.

Chronic mucosal injury

Achalasia, previous caustic injury, head-and-neck squamous cancer and certain nutritional or thermal exposures increase squamous-cancer risk after prolonged stasis or inflammation.

Inherited and treatment-related factors

Rare tylosis and DNA-repair syndromes, prior thoracic radiotherapy and longstanding immune or inflammatory conditions can confer additional risk in selected patients.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Histology follows anatomical exposure
Adenocarcinoma usually arises in distal Barrett mucosa, whereas squamous dysplasia can develop throughout the oesophagus and remains common in upper and mid segments.
2
Submucosal spread occurs early
Longitudinal lymphatic channels allow tumour and nodal dissemination beyond the visible mucosal margin, complicating local staging and resection planning.
3
Luminal narrowing causes dysphagia
Progressive circumferential growth reduces distensibility, first obstructing solids and eventually liquids, while proximal stasis promotes regurgitation and aspiration.
4
Local invasion creates fistula and pain
Extension into tracheobronchial tree, aorta, pleura, pericardium, recurrent-laryngeal nerve or vertebrae causes cough, bleeding, hoarseness and unresectability.
5
Distant spread follows lymph and blood
Cervical, mediastinal and coeliac nodes and liver, lung, bone, adrenal and peritoneal metastases determine prognosis and shift treatment toward systemic control.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Mechanical dysphagia

Progression from solid-food sticking to difficulty with soft food and liquids suggests a narrowing lesion rather than simple reflux.

Proximal or squamous pattern

Higher dysphagia, aspiration, hoarseness and strong tobacco or alcohol exposure support upper or mid squamous disease but do not establish histology.

Distal adenocarcinoma pattern

Long reflux, Barrett history, central obesity and lower retrosternal food hold-up increase probability of distal or junctional adenocarcinoma.

Advanced local invasionRed flag

Chest or back pain, hoarseness, stridor, cough on swallowing or haemoptysis suggests neural, airway or mediastinal extension.

Metastatic presentation

Supraclavicular node, hepatomegaly, jaundice, pleural fluid, bone pain, ascites or cachexia indicates possible systemic spread.

Complete obstructionRed flag

Inability to swallow saliva, pooling secretions, dehydration and aspiration requires urgent airway, fluid, nutrition and endoscopic assessment.

Red flags requiring action

Progressive dysphagia, especially solids followed by liquids, requires urgent upper-GI endoscopy and biopsy rather than empirical reflux treatment.
Inability to swallow saliva, dehydration, aspiration or rapid nutritional decline requires same-day assessment and a safe route for fluids and nutrition.
Cough on swallowing, recurrent pneumonia, haemoptysis or air seen within tumour raises tracheo-oesophageal fistula.
Haematemesis, melaena, syncope or falling haemoglobin indicates tumour bleeding or another upper-GI haemorrhage.
Hoarseness, Horner syndrome, vertebral pain or airway stridor suggests recurrent-laryngeal, sympathetic, spinal or tracheobronchial invasion.
Severe chest pain, fever, subcutaneous emphysema or shock after endoscopy or stenting suggests perforation and mediastinal sepsis.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
First-line upper-GI endoscopy with biopsyFirst stepFirst line
Why
Locate and characterise tumour, assess obstruction and obtain multiple tissue samples for definitive histology.
Interpretation and limitations
Record distance from incisors and junction, length and circumferential extent; repeat or use image-guided sampling if biopsies are superficial or necrotic and suspicion remains.
02
First-line contrast CT chest and abdomenFirst line
Why
Assess local mediastinal relationships, regional nodes, liver, lung, adrenal and other distant disease and identify biopsy targets.
Interpretation and limitations
CT cannot reliably distinguish all wall layers or reactive nodes; a potentially curable case proceeds to PET-CT and selective EUS.
03
PET-CT for radical-intent staging
Why
Detect metabolically active nodal or distant metastasis not apparent on CT and define radiotherapy or biopsy targets.
Interpretation and limitations
Inflammation can be avid and small or mucinous metastases can be occult; confirm a solitary high-consequence lesion where feasible.
04
Endoscopic ultrasound with selected FNA
Why
Resolve T wall depth and regional-node status when the result will change endoscopic, surgical or radiation treatment.
Interpretation and limitations
Severe stenosis may prevent passage and post-biopsy inflammation can alter appearances; sample a node only when it changes management and does not traverse tumour unnecessarily.
05
Bronchoscopy or staging laparoscopy
Why
Assess airway invasion in upper or middle lesions and occult peritoneal disease in selected junctional adenocarcinoma.
Interpretation and limitations
Use by anatomical risk rather than routinely; cytology or biopsy of suspicious findings can prevent non-beneficial radical surgery.
06
Predictive biomarkers in advanced disease
Why
Select targeted and immune treatment from HER2, PD-L1 and mismatch-repair or microsatellite findings.
Interpretation and limitations
Test the histology and line-specific markers with validated scoring, recognising intratumour heterogeneity and retesting when earlier tissue is inadequate.
07
Nutrition and operative fitness
Why
Identify sarcopenia, aspiration, micronutrient and cardiopulmonary limitations before intensive multimodality treatment.
Interpretation and limitations
Include dietitian assessment, weight trajectory, swallowing safety, FBC and organ function and exercise or cardiopulmonary testing for oesophagectomy candidates.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Benign stricture or ring

Peptic narrowing, Schatzki ring and postoperative or radiation strictures cause structural dysphagia but still require endoscopic exclusion of malignancy when new or progressive.

Motility disorder

Achalasia, spasm and scleroderma can affect solids and liquids early; pseudoachalasia from junctional cancer must be excluded in older patients or rapid weight loss.

Inflammatory oesophagitis

Reflux, eosinophilic, pill, infective and caustic injury can cause odynophagia and narrowing; endoscopic biopsy distinguishes inflammatory and malignant mucosa.

Extrinsic compression

Mediastinal nodes, lung cancer, aortic enlargement, left atrial enlargement and thyroid or cervical masses can narrow the oesophagus from outside.

Oropharyngeal dysphagia

Difficulty initiating swallow, nasal regurgitation, choking and neurological signs localise above the oesophagus and require swallowing and neurological assessment.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01DysphagiaObtain tissue before symptom-only treatmentFirst stepAn adult develops progressive dysphagia, food sticking, weight loss or another alarm upper-GI symptom.

1Assess hydration, aspiration, ability to swallow saliva, bleeding and nutrition and arrange urgent endoscopy rather than a prolonged empirical acid-suppression trial.
2Biopsy the lesion adequately and use targeted CT or ultrasound-guided sampling if endoscopic tissue is non-diagnostic or a metastatic site is safer.
3Communicate histology promptly, obtain CT staging and refer to the specialist oesophago-gastric MDT with dietetic support from diagnosis.

02Curative stagingExclude occult spread before major treatmentHistology confirms cancer and CT shows no definite unresectable or distant disease.

1Obtain PET-CT and selective EUS, bronchoscopy or staging laparoscopy according to level, histology and the decisions that remain unresolved.
2Confirm a solitary distant or unresectable finding with tissue when feasible and high consequence, and assess cardiopulmonary, frailty, nutrition and patient preference.
3DefinitiveSelect endoscopic resection, perioperative chemotherapy and surgery, neoadjuvant chemoradiation and surgery or definitive chemoradiation in the specialist MDT.

03Early mucosalPreserve the oesophagus when invasion is superficialStaging suggests a small mucosal neoplasm without nodal or distant disease.

1Perform expert endoscopic mucosal resection or submucosal dissection to obtain an en-bloc or complete specimen that defines depth, grade, lymphovascular invasion and margins.
2DefinitiveUse definitive histology to decide whether endoscopic treatment is curative or whether submucosal invasion or adverse features require oesophagectomy or chemoradiation discussion.
3For Barrett-associated neoplasia, eradicate residual dysplastic Barrett mucosa and enter structured endoscopic surveillance after healing.

04Advanced diseaseSequence systemic and swallowing treatmentDisease is metastatic, unresectable or the patient is not suitable for radical therapy.

1Test histology-appropriate biomarkers, assess performance, organ function, dysphagia speed and goals and choose the current funded systemic regimen with predefined review.
2Use stent for rapid relief when appropriate, radiation or brachytherapy for a slower durable effect and feeding access when oral intake cannot safely meet need, avoiding procedures that conflict with future treatment.
3Integrate analgesia, secretion and reflux control, aspiration prevention, bleeding planning, nutrition and palliative care and stop ineffective toxic therapy promptly.

05Fistula or obstructionProtect airway and establish a safe routeThe patient cannot swallow saliva or has aspiration, pneumonia or suspected airway communication.

1Keep nil by mouth, sit upright, give suction, oxygen, fluids and antibiotics as indicated and obtain urgent CT and joint respiratory and upper-GI assessment.
2Define oesophageal and airway anatomy with controlled endoscopy or bronchoscopy and select oesophageal, airway or dual stenting, radiotherapy, drainage or surgery according to level and perforation risk.
3Establish safe enteral or parenteral nutrition and provide explicit aspiration and emergency instructions before discharge.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

Treats micrometastatic disease around resection of suitable locally advanced distal oesophageal or gastro-oesophageal-junction adenocarcinoma.

Perioperative FLOT for eligible adenocarcinoma

A common 14-day specialist cycle gives docetaxel 50 mg/m², oxaliplatin 85 mg/m² and leucovorin 200 mg/m² intravenously on day 1 followed by fluorouracil 2,600 mg/m² over 24 hours, usually four cycles before and four after surgery.

Use the exact NHS protocol with DPD status, marrow, renal, liver, neuropathy, infection, mucositis, diarrhoea, thrombotic and nutritional monitoring and reassess postoperative fitness before resuming.

Radiosensitises resectable oesophageal or junctional cancer before surgery and can inform related definitive protocols when surgery is not planned.

Weekly carboplatin and paclitaxel with radiotherapy

A common neoadjuvant chemoradiation protocol gives carboplatin AUC 2 and paclitaxel 50 mg/m² intravenously once weekly for 5 weeks during 41.4 Gy radiotherapy, with exact dates and fields set by the specialist protocol.

Monitor marrow, infection, neuropathy, hypersensitivity, swallowing, dehydration and radiation oesophagitis and avoid applying a neoadjuvant dose or field unchanged to a definitive-intent regimen.

Provides PD-1 blockade for selected advanced oesophageal squamous carcinoma or adenocarcinoma and mismatch-repair-deficient disease.

Pembrolizumab in eligible advanced disease

Give pembrolizumab 200 mg intravenously every 3 weeks or 400 mg every 6 weeks, alone or with protocol chemotherapy only within the licensed histology, PD-L1 or mismatch-repair and current NICE-funded indication.

Assess autoimmune and transplant history and monitor for lung, bowel, liver, endocrine, renal, cardiac, skin and neurological immune toxicity; investigate infection and progression concurrently with suspected immune events.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Malnutrition and sarcopenia

Reduced intake, catabolism and treatment toxicity cause weight and muscle loss, impairing surgical recovery, chemotherapy tolerance and independence.

Aspiration and fistulation

Proximal stasis or tumour communication with airway causes recurrent pneumonia, sepsis, respiratory failure and distressing cough with eating.

Bleeding and perforation

Friable tumour, treatment necrosis or intervention can cause occult anaemia, major haemorrhage, mediastinitis or communication with adjacent structures.

Metastatic organ disease

Liver, lung, bone, brain, adrenal and peritoneal spread causes pain, jaundice, effusions, fracture, neurological symptoms and progressive cachexia.

Post-treatment functional morbidity

Anastomotic leak or stricture, reflux, dumping, delayed gastric emptying, pulmonary complications and radiation injury can persist after curative therapy.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Track swallowing by food texture, aspiration, weight, muscle mass, hydration and intake at every stage rather than relying on body weight alone.
During chemoradiation, review blood count, organ function, pain, mucositis, candidiasis, reflux, dehydration, skin and respiratory symptoms at least weekly.
After oesophagectomy, monitor leak, conduit perfusion, pneumonia, atrial fibrillation, chyle leak and nutrition early and stricture, reflux, dumping and weight loss later.
After endoscopic resection and Barrett eradication, use the pathology-defined endoscopic surveillance schedule and biopsy recurrent visible or dysplastic mucosa.
During advanced treatment, assess symptoms and organ function with interval CT and biomarker-specific toxicity; avoid continuing solely because tumour diameter is stable while function worsens.
After stenting, review pain, reflux, migration, food bolus, aspiration, bleeding and fistula and provide written food-texture and emergency advice.
Maintain smoking and alcohol support, dental and nutritional care and rapid access for recurrent dysphagia, bleeding, chest pain or respiratory symptoms.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Dysphagia level can mislead

Patients may perceive obstruction above the true lesion, so symptom location should not determine which segment is examined.

Pseudoachalasia must be excluded

New achalasia-like findings in an older patient with rapid weight loss can reflect junctional tumour infiltrating the myenteric plexus.

EUS is a decision tool

It adds wall and nodal detail only after distant disease is excluded and when the answer could change endoscopic, surgical or radiation intent.

A stent is not neutral

Rapid swallowing relief comes with migration, pain, reflux, perforation and later-treatment consequences, so expected survival and intent shape selection.

Nutrition route affects surgery

A feeding procedure can injure a future gastric conduit or increase aspiration, requiring upper-GI and dietetic planning rather than reflex tube placement.

Squamous and adenocarcinoma are distinct

They differ in exposure, location, biomarker, radiation sensitivity and systemic sequences, so the word oesophageal does not define one treatment plan.

11Common pitfallsFrequent interpretation and management errors.

01
Treating progressive dysphagia as reflux without urgent endoscopy.
02
Accepting superficial negative biopsies from a visible suspicious stricture without repeat or alternative tissue.
03
Using EUS as the first staging test before identifying distant disease on CT or PET-CT.
04
Abandoning curative treatment for one unconfirmed PET-avid distant focus.
05
Applying the same systemic regimen to squamous and adenocarcinoma without biomarker and junction review.
06
Placing a stent reflexively before a potentially curative operation or chemoradiation course.
07
Starting intensive therapy before nutrition, aspiration and cardiopulmonary fitness are addressed.
08
Choosing feeding access without considering the future gastric conduit.
09
Equating radiological stability with benefit despite worsening dysphagia and performance.