Esophageal Cancer Overview

Esophageal Cancer

• Anatomy: Esophagus extends from the Upper Esophageal Sphincter (UES) to the Esophagogastric Junction (GEJ).
• Average resting lumen size: 2cm (AP) x 3cm (laterally).
• UES is approximately 15cm from incisors, and GEJ is approximately 40cm from incisors.
• Esophagus divided into cervical, thoracic (upper, middle, lower), and abdominal sections.
• No serosa.
• Blood supply from segmental end-arteries.
• Lymphatic system abundant in submucosal plane.
• Regional nodal basins: cervical, thoracic, and abdominal.
• Cervical nodes include recurrent laryngeal, jugular, and supraclavicular.
• Thoracic nodes include thoracic duct and subcarinal.
• Abdominal nodes include celiac, left gastric, splenic, common hepatic, lesser curve, retroperitoneal, and diaphragmatic.

Epidemiology of Esophageal Cancer

• Males are affected more than females (3:1 ratio).
• Typically diagnosed between 60-70 years.
• 6th leading cause of cancer death globally.
• Incidence varies geographically with highest rates in Central Asia and Northern China.
• Adenocarcinoma more common in USA, increasing in prevalence.
• Squamous cell carcinoma (SCC) most prevalent globally.
• Overall 5-year survival rate approximately 18%.

Definition of Esophageal Cancer

• Esophageal Cancer: Tumor epicenter within the esophagus, lower extent >2cm from EGJ.
• GE Junction Cancer: Tumor lower extent within 2cm of GEJ, involving any portion of esophagus.
• Gastric Cancer: Tumor epicenter >2cm below GEJ.
• Siewert Classification: Categorizes esophagogastric cancers based on tumor location (I, II, and III) regarding treatment approach.

Risk Factors

• Adenocarcinoma:*

• Barrett's esophagus: Significant risk factor (30-60x).

• Gastroesophageal Reflux Disease (GERD): Increased risk with increased symptom duration.

• Smoking: Double the risk.

• Obesity: Triple the risk.

• Male sex: Triple the risk.

• Radiation therapy history: 5x higher risk.

• Genetic mutations (e.g., TP53, ARID1A, SMAD4): Associated with esophageal adenocarcinoma.

• Squamous Cell Carcinoma (SCC):*

• Smoking: Quadruple the risk.

• Alcohol: Pentaple the risk.

• Smoking and Alcohol: Synergistic effect, significantly increasing risk (44x).

• Male sex: Double the risk.

• Age: Risk increases with age.

• Plummer-Vinson syndrome: Associated with risk.

• Achalasia, Zenker's Diverticula: Elevated risk due to stasis and inflammation.

• Tylosis, HPV 16: Increased risk.

• Genetic mutations (e.g., TP53, CCND1, MDM2): Associated with SCC.

Biomarker Screening

• HER2: Protein linked to potential aggressive cancer behavior with variations in prevalence across cancer types. Screening with IHC/ISH is recommended for diagnosis.
  • Poorer prognosis, more aggressive tumor invasion, lymph node spread are associated with HER2 positivity.
• MSI/MMR: Mutation detection is particularly considered for recurrent, locally advanced, or metastatic cases. It's helpful for determining the role of PD-1 inhibitors in treatment.
• PD-L1: Useful in advanced stages, evaluated with IHC, to determine the potential use of PD-1 inhibitors.

Genetic Syndromes

• Tylosis (Howell-Evans syndrome): Rare, autosomal dominant condition with elevated risk of esophageal SCC, requiring screening from 20 years.
• Familial Barrett's Esophagus: Clustering of cases within families, predisposes to esophageal adenocarcinoma. Screening starting at 40 years recommended for high risk groups.
• Bloom's Syndrome and Fanconi Anemia: Rare, inherited conditions increasing risk for various cancers, including esophageal SCC, warranting regular endoscopic screening.

Barrett's Esophagus

• Epidemiology: 5% of US population, 1% globally.
• Risk Factors: Age, obesity, GERD duration, male sex, white race, tobacco, familial history, and hiatal hernias.
• Pathology: Substitution of squamous epithelium with intestinal-type epithelium.
• Natural History: Progression to dysplasia and cancer. Risk of progression depends on grade.
• Presentation: Reflux symptoms, sometimes asymptomatic.
• Diagnosis: Endoscopy, biopsies, potentially WATS3D, other advanced endoscopy options for diagnosis.
• Management: PPI, NSAIDs, aspirin, endoscopic removal/ablation for dysplasia, surveillance.
• Surveillance: Different frequency/biopsy approaches according to Barrett's dysplasia grade.