7. Oesophageal Cancer

 

 

Incidence and Epidemiology

  • Prevalence: 7th most common cancer globally with 604,000 new cases in 2020.
  • Mortality: 6th leading cause of cancer-related deaths (~544,000 in 2020).
  • Demographics: Higher incidence in men (70% of diagnoses).
  • Geographic Variation: Higher rates in Eastern Asia, Southern Africa, and Northern Europe.
  • Subtypes:
    • Squamous Cell Carcinoma (SCC): ~90% of global cases.
    • Adenocarcinoma (AC): Increasing in North America and Europe due to lifestyle and dietary changes.

Risk Factors

  • Adenocarcinoma (AC):
    • Obesity, GERD, Barrett’s esophagus, positive family history, smoking, radiation therapy (RT), male gender, advanced age.
    • Lower esophageal sphincter (LOS) relaxers: nitrates, anticholinergics, beta-agonists, aminophylline, benzodiazepines.
  • Squamous Cell Carcinoma (SCC):
    • Alcohol, smoking (synergistic effect), poor oral hygiene, socioeconomic deprivation.
    • Nutritional deficiencies (zinc, selenium), palmoplantar keratoderma, and potentially HPV.
    • Geographic-specific factors: betel quid chewing (India), hot beverage consumption (Iran, Tanzania).

Pathophysiology

  • SCC: Arises from squamous epithelium.
  • AC: Develops in the context of Barrett’s esophagus or GERD, often involving intestinal metaplasia.

Classification of Tumors

T-Stage Definitions

  • T1a:
    • M1: Carcinoma in situ.
    • M2 (LPM): Invasion into the lamina propria.
    • M3 (MM): Invasion into the muscularis mucosa.
    • Management: Endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) if >2cm.
  • T1b:
    • SM1: Invasion into the upper third of the submucosa.
    • SM2: Invasion into the middle third of the submucosa.
    • SM3: Invasion into the lower third of the submucosa.
    • Management: Involvement of submucosa increases lymphatic spread risk; radical surgery required if M0.
  • T2-T3: Tumor invades the muscularis propria (T2) or adventitia (T3).
  • T4a: Involvement of pleura, pericardium, azygous vein, or diaphragm.
  • T4b: Involves trachea/bronchi, vertebral body, or major vessels (e.g., aorta).

Diagnostic Approach

Key Investigations

Procedure

Purpose

Upper GI endoscopy

Detect lesions, confirm previous findings, and obtain biopsy (≥6 samples).

Histopathology

Differentiate SCC vs. AC; assess for neuroendocrine/melanocytic tumors.

Immunohistochemistry (IHC)

PD-L1 testing for checkpoint inhibitor eligibility (e.g., TPS ≥1%, CPS ≥10).

Endoscopic ultrasound (EUS)

T/N staging, lymph node biopsies, and tumor layer invasion assessment.

Bronchoscopy (with EUS)

Check posterior tracheal involvement (upper two-thirds tumors).

CT (thorax, abdomen, pelvis)

Evaluate local invasion, nodal status, and distant metastasis.

PET-CT

Detect distant metastases if CT is negative.

Laparoscopy

Identify peritoneal metastases (OGJ tumors crossing diaphragm).

Guidelines for Diagnosis:

  • Initial Staging:
    • CT Scan: Essential to evaluate for distant metastases.
    • PET-CT: Used if CT is negative to confirm no metastases.
    • EUS: Performed after CT for loco-regional staging.
      • Less accurate for early mucosal disease staging.
      • Recommended to stage T1 tumors or high-grade dysplasia via endoscopic resection for precise depth assessment.
    • Special Considerations:
      • Dilating tumors is not recommended unless necessary (e.g., coeliac lymph node FNA).
      • Coordination with surgical teams is crucial to avoid complications.

Staging and Risk Assessment

  • System Used: AJCC/UICC TNM 8th edition.
  • Essential Components:
    • Physical examination.
    • FDG-PET: Preferred for detecting distant metastases.
    • EUS: Recommended for evaluating T4b status and lymph node involvement.
    • Laparoscopy: Used for peritoneal spread assessment in locally advanced OGJ tumors.

Nutritional and Functional Evaluation

  • 50% of patients experience >5% body weight loss pre-surgery.
  • Follow ESPEN guidelines for early nutritional support [II, A].
  • Prehabilitation improves physical fitness and QoL [III, A].
  • Geriatric assessment improves chemotherapy tolerance predictions [III, B].

Management of Localized and Locoregional Disease

Multidisciplinary Team (MDT) Assessment

  • Treatment tailored to:
    • Histology (SCC vs. AC).
    • Clinical TNM stage.
    • Tumor location.
    • Performance status.

Early Disease (T1 N0 M0)

  • Endoscopic Resection (preferred for T1 tumors):
    • Techniques: EMR or ESD.
    • Indications: High-grade dysplasia or T1a tumors without lymph node metastasis.
    • Factors for Additional Treatment: Submucosal invasion (T1b+), poor differentiation, lymphovascular invasion.

Locally Advanced Disease (T2-T4, N+ M0)

  • Surgery:
    • Radical transthoracic esophagectomy with two-field lymphadenectomy.
    • Minimally Invasive Esophagectomy (MIO): Shown to reduce morbidity and improve QoL.

Neoadjuvant/Perioperative Therapy

Histology

Recommended Regimen

Evidence Level

SCC

Preoperative CRT (CROSS regimen)

I, A

AC

Perioperative FLOT chemotherapy

I, A

SCC (cervical)

Definitive CRT (organ preservation)

III, B

Adjuvant Nivolumab:

  • Indicated for residual disease after neoadjuvant CRT (CheckMate 577).

Definitive Chemoradiotherapy (CRT)

  • Standard Regimen: Cisplatin + 5-FU or carboplatin-paclitaxel with 50.4 Gy radiation.
  • Considerations:
    • RT dose escalation >50.4 Gy not recommended due to increased toxicity.
    • Salvage Esophagectomy: Performed for persistent disease [II, B].

Management of Advanced/Metastatic Disease

First-Line Therapy

  • Standard Chemotherapy: Platinum-fluoropyrimidine doublet [II, A].
  • Combination with ICIs (Checkpoint Inhibitors):
    • Pembrolizumab + Chemotherapy (KEYNOTE-590).
    • Nivolumab + Chemotherapy (CheckMate 648).

PD-L1 Subgroup Recommendations:

PD-L1 CPS

Treatment

Grade

≥10

Pembrolizumab-Cisplatin/5-FU

I, A

≥1% (TPS)

Nivolumab-Cisplatin/5-FU

I, A

Second-Line Therapy

  • Nivolumab monotherapy (ATTRACTION-3 trial).
  • Pembrolizumab for CPS ≥10 if ICI-naïve.
  • Chemotherapy: Taxane or irinotecan for fit patients [II, B].

Supportive Care

  • Early referral to palliative care.
  • Nutritional intervention following ESPEN guidelines.
  • Endoscopic stenting for palliation (in advanced disease).

Follow-Up and Survivorship

Surveillance

  • Majority (~90%) of relapses occur within 2 years.
  • Endoscopy, biopsies, and CT scans recommended every 3 months post-CRT for early recurrence.

Long-Term Care

  • Address nutrition, psychosocial needs, and rehabilitation.
  • Monitor for metachronous malignancies.

References

  1. ESMO Clinical Practice Guidelines
  2. Annals of Oncology (Obermannová et al., 2022)
  3. KEYNOTE and CheckMate studies for immunotherapy efficacy.

 

 

Images examples:

Figure 1. Oesophageal Stricture


Figure 3. Oesophageal Pappiloma