ESOPHAGEAL CANCER

ESOPHAGEAL CANCER

AT A GLANCE

Major histologies	Squamous cell carcinoma (SCC) and adenocarcinoma (AC).
Classic presentation	Progressive dysphagia, usually solids → liquids, with weight loss.
Diagnosis	Upper GI endoscopy with multiple biopsies.
Staging	Contrast CT chest/abdomen ± pelvis; FDG PET-CT when potentially curable; EUS for locoregional T/N assessment when feasible.
Early disease	Selected superficial T1a lesions may be treated endoscopically.
Locally advanced AC	Perioperative FLOT is the current key ESMO approach for fit patients; neoadjuvant CRT is an alternative when FLOT is unsuitable.
Locally advanced SCC	Neoadjuvant CRT + surgery or definitive CRT in selected patients.
Advanced disease	Histology- and biomarker-directed systemic therapy + nutrition and symptom control.
MDT principle	All potentially curable patients should undergo specialist multidisciplinary assessment.

Table of Contents

1. DEFINITION

Esophageal cancer is a malignant epithelial neoplasm arising in the esophagus. The two dominant histologies are squamous cell carcinoma and adenocarcinoma.

2. EPIDEMIOLOGY & RISK FACTORS

Squamous cell carcinoma	Adenocarcinoma
Tobacco smoking	Chronic GERD
Alcohol; synergistic with tobacco	Barrett’s esophagus
Achalasia	Obesity, particularly central adiposity
Caustic/chronic mucosal injury	Smoking
Prior thoracic/mediastinal radiation	Hiatal hernia / reflux phenotype
Geographic, nutritional and environmental factors	Increasing age and male predominance

3. HISTOLOGY & ANATOMIC DISTRIBUTION

Feature	SCC	Adenocarcinoma
Typical location	Upper/middle thoracic	Distal esophagus/EGJ
Precursor	Squamous dysplasia	Barrett’s metaplasia → dysplasia
Major associations	Tobacco, alcohol, achalasia	GERD, Barrett’s, obesity
Treatment distinction	Definitive CRT is an established curative pathway in selected patients	Perioperative systemic therapy is central for resectable locally advanced disease

4. CLINICAL FEATURES

Progressive dysphagia—classically solids → semisolids → liquids as obstruction progresses.
Weight loss
Odynophagia, retrosternal pain/discomfort, regurgitation or vomiting.
GI bleeding or iron-deficiency anemia.
Hoarseness suggests recurrent laryngeal nerve involvement.
Cough/choking with swallowing suggests aspiration or tracheobronchial involvement.
Persistent cough, recurrent pneumonia, hemoptysis or severe chest/back pain may indicate advanced disease or fistulization.

CLINICAL PEARL: Progressive dysphagia with weight loss is an alarm presentation. Do not manage it as uncomplicated GERD without prompt evaluation.

5. DIFFERENTIAL DIAGNOSIS OF DYSPHAGIA

Differential	Clues
Peptic/benign esophageal stricture	Long GERD history; usually slower progression
Achalasia / pseudoachalasia	Dysphagia to solids and liquids; weight loss in pseudoachalasia
Eosinophilic esophagitis	Food impaction, atopy, younger patients
Extrinsic compression	Abnormal imaging; symptoms may be variable
Esophageal motility disorder	Dysphagia to solids and liquids without fixed obstruction
Inflammatory/infectious esophageal disease	Odynophagia often prominent

6. DIAGNOSIS — ENDOSCOPY FIRST

Upper GI endoscopy is the diagnostic test of choice.
Document distance from incisors, location, longitudinal length, circumferential extent, surface morphology and degree of luminal narrowing.
Take multiple targeted biopsies for histology.
If initial biopsies are nondiagnostic despite high suspicion, repeat targeted biopsy and continue appropriate imaging/MDT evaluation.
Do not assume a malignant-appearing stricture is benign.
Histology should distinguish SCC from adenocarcinoma and report differentiation/grade where appropriate.

7. ENDOSCOPIC DESCRIPTION

Document	Why it matters
Exact location + distance from incisors	Staging, surgical approach and radiation planning
Relation to GEJ	Critical for distal/GEJ tumors and adenocarcinoma classification
Length and circumference	Tumor burden and technical resectability
Ulceration/exophytic growth	Supports invasive disease and guides biopsy
Lumen traversable or not	Influences EUS and procedural strategy
Biopsy adequacy	Required for definitive diagnosis

8. PRE-TREATMENT STAGING

Investigation	Main role
Contrast CT chest + abdomen ± pelvis	Local extension, nodes and distant disease
FDG PET-CT	Detect occult distant metastases in potentially curable disease; complements CT
EUS	High-value T and regional N assessment when technically feasible
Bronchoscopy	Upper/mid tumors or suspected tracheobronchial invasion
Laryngoscopy/ENT assessment	Cervical/proximal tumors or hoarseness
CBC, renal/liver function, nutrition	Treatment readiness and fitness
Biomarker testing	Essential in advanced disease; panel depends on histology and treatment pathway

9. TNM — PRACTICAL STAGE FRAMEWORK

Category	High-yield meaning
Tis	High-grade dysplasia / carcinoma in situ
T1a	Tumor limited to lamina propria or muscularis mucosae
T1b	Tumor invades submucosa; nodal risk is higher than T1a
T2	Invades muscularis propria
T3	Invades adventitia
T4a	Invades resectable adjacent structures
T4b	Invades unresectable adjacent structures
N	Regional lymph-node involvement; formal N category should follow current AJCC/UICC edition
M1	Distant metastasis

Use the current AJCC/UICC TNM manual for formal stage grouping; histology and tumor location can influence stage grouping.

10. EARLY ESOPHAGEAL CANCER

Finding	Approach
Selected mucosal T1a lesion without high-risk features	Endoscopic resection (EMR/ESD) may be definitive
Superficial SCC requiring en-bloc histology	ESD is often preferred when technically appropriate
Visible Barrett’s-related neoplasia	Resect visible lesion and manage residual Barrett’s neoplasia according to specialist protocol
Deep submucosal invasion, LVI, poor differentiation or involved margins	MDT review for additional oncologic therapy/surgery; endoscopic resection alone may be non-curative

HIGH-YIELD: The endoscopic resection specimen is both therapeutic and a staging specimen. Depth, differentiation, margins and lymphovascular invasion determine whether additional treatment is required.

11. MANAGEMENT

Clinical setting	Management pathway
T1a, low-risk superficial disease	Endoscopic resection (EMR/ESD) → expert histology → surveillance or additional therapy if high-risk pathology
Resectable locally advanced AC	Perioperative FLOT → surgery. Neoadjuvant CRT may be considered when FLOT is unsuitable.
Resectable locally advanced SCC	Neoadjuvant CRT → esophagectomy OR definitive CRT in selected patients.
Cervical/proximal SCC	Definitive CRT is commonly favored when surgery would require major morbidity/laryngectomy.
Unresectable locally advanced disease	Definitive CRT when appropriate; reassess response and consider salvage strategies in selected patients.
Metastatic SCC	Systemic therapy based on current guideline, PD-L1 status where relevant, prior therapy and fitness + early supportive/palliative care.
Metastatic AC	Systemic therapy guided by HER2, PD-L1, MSI/MMR and other actionable biomarkers where relevant.
Any stage with severe dysphagia/malnutrition	Early nutrition assessment + individualized enteral/endoscopic/radiologic palliation.

ESMO 2025 update: perioperative FLOT is recommended for most fit patients with resectable locally advanced esophageal/OGJ adenocarcinoma; neoadjuvant CRT is an alternative when FLOT is unsuitable.

12. ADJUVANT NIVOLUMAB — CHECKMATE 577

After neoadjuvant CRT and R0 resection, patients with residual pathologic disease (≥ypT1 and/or ≥ypN1) may receive adjuvant nivolumab.
Do not apply this indication to patients with pathologic complete response under the same indication.
Verify current regulatory labeling and local oncology protocol before prescribing.

13. METASTATIC / UNRESECTABLE DISEASE

Histology	Key approach
ESCC	Platinum–fluoropyrimidine chemotherapy ± immune checkpoint inhibitor according to current biomarker/regulatory pathway.
Adenocarcinoma	Systemic therapy guided by HER2, PD-L1, MSI/MMR and other actionable biomarkers where relevant.
All patients	Assess performance status, organ function, nutrition, swallowing, symptoms and patient goals.

14. PALLIATION OF MALIGNANT DYSPHAGIA

Problem	Practical option
Need rapid swallowing relief	Self-expanding metal stent in appropriate patients
Longer expected survival / local control	Radiotherapy or selected endoscopic approaches
Severe nutritional compromise	Early nutrition-team assessment; enteral feeding when appropriate
Tracheoesophageal fistula	Urgent MDT assessment; esophageal ± airway stenting may be required
Pain / bleeding	Individualized analgesic, endoscopic, radiologic or oncologic palliation

Palliative stenting is primarily for symptom relief. Discuss migration, bleeding, perforation, tumor overgrowth and fistula-related risks.

15. IMPORTANT COMPLICATIONS

Complication	Clue	Immediate priority
Obstruction	Progressive dysphagia/regurgitation	Assess nutrition and palliate obstruction
Aspiration	Cough during/after swallowing, recurrent pneumonia	Aspiration precautions + swallowing/nutrition assessment
Tracheoesophageal fistula	Cough immediately after swallowing + recurrent infection	Urgent MDT; consider esophageal/airway stenting
Airway invasion	Dyspnea, hemoptysis, recurrent pneumonia	Airway assessment + MDT
Recurrent laryngeal nerve palsy	Hoarseness	ENT/laryngeal assessment
Bleeding	Hematemesis, melena or anemia	Stabilize + individualized hemostatic/palliative strategy
Malnutrition/cachexia	Weight loss, weakness, reduced intake	Early nutrition intervention
Metastatic disease	Liver, lung, bone or other distant involvement	Stage and initiate appropriate systemic/palliative pathway

16. WHAT HAS CHANGED / MODERN PRACTICE

Perioperative systemic therapy has become central for resectable locally advanced adenocarcinoma in appropriate patients.
Management is increasingly biomarker-driven in advanced disease.
Endoscopic resection is established for carefully selected superficial cancers.
Immune checkpoint inhibitors have moved into defined curative-intent and advanced-disease settings.
Nutrition, sarcopenia and functional status are important determinants of treatment tolerance and outcomes.

17. REFERENCES — CORE READING

Harrison’s Principles of Internal Medicine, 22nd ed. (2025): Chapter 85, Upper Gastrointestinal Tract Cancers; Chapter 334, Diseases of the Esophagus.
Sleisenger and Fordtran’s Gastrointestinal and Liver Disease, 12th ed. (Elsevier, 2026): Chapter 46, Tumors of the Esophagus.
Obermannová RL, Leong T; ESMO Guidelines Committee. ESMO Clinical Practice Guideline interim update on locally advanced oesophageal/oesophagogastric-junction adenocarcinoma and metastatic squamous-cell carcinoma. ESMO Open. 2025;10(2):104134.
ESMO Clinical Practice Guideline: Oesophageal cancer—diagnosis, treatment and follow-up. Annals of Oncology. 2022.
ESGE Guideline: Endoscopic submucosal dissection for superficial gastrointestinal lesions—Update 2022.
AJCC/UICC current TNM staging manual—use the current edition for formal stage assignment.
NCI PDQ: Esophageal Cancer—Health Professional Version.