Esophageal Cancer

For further information, see CMDT Part 39-09: Esophageal Cancer

Essentials of Diagnosis

• Progressive dysphagia to solid food

• Weight loss

• Endoscopy with biopsy establishes diagnosis

General Considerations

• Two histologic types

  • Squamous cell carcinoma: occurs throughout esophagus; half occur in distal third

  • Adenocarcinoma: most arise near the gastroesophageal junction

• Squamous cell cancer risk factors

  • Chronic alcohol and tobacco use

  • Tylosis

  • Achalasia

  • Caustic-induced esophageal stricture

  • Other head and neck cancers

• Adenocarcinoma risk factors

  • Barrett metaplasia due to chronic gastroesophageal reflux

  • Obesity

Demographics

• Occurs usually in persons between 50 and 70 years of age

• Ratio of men to women is 3:1

• About 17,920 new cases of esophageal cancer were diagnosed in 2018

• Squamous cell carcinoma is common in Eastern Europe and Asia

• Adenocarcinoma is more common in North America and most Western European countries

Symptoms and Signs

• Solid food dysphagia (> 90%)

• Odynophagia

• Significant weight loss

• Coughing on swallowing or recurrent pneumonia suggests tracheoesophageal fistula from local tumor extension

• Chest or back pain suggest mediastinal extension

• Hoarseness suggests recurrent laryngeal nerve involvement

• Physical examination often unrevealing

• Supraclavicular or cervical lymphadenopathy or hepatomegaly suggests metastatic disease

Differential Diagnosis

• Peptic stricture

• Achalasia

• Adenocarcinoma of gastric cardia with esophageal involvement

• Esophageal web, ring (eg, Schatzki), or diverticulum

Laboratory Tests

• Anemia related to chronic disease or occult blood loss

• Elevated aminotransferase or alkaline phosphatase suggest hepatic or bony metastases

• Hypoalbuminemia

Imaging Studies

• Chest radiographs may show adenopathy

• Barium esophagogram

• Contrast CT of the chest and abdomen to look for evidence of pulmonary or hepatic metastases, lymphadenopathy, and local tumor extension

• Positron emission tomography with fluorodeoxyglucose (FDG-PET) or integrated PET-CT imaging is indicated to look for regional or distant spread in patients thought to have localized disease after other diagnostic studies

Diagnostic Procedures

• Upper endoscopy with biopsy

• Endoscopic ultrasonography with guided fine-needle aspiration (FNA) of lymph nodes is superior to CT for evaluating local extension and lymph node involvement

• Bronchoscopy may be required to exclude tracheobronchial extension

• Laparoscopy to exclude occult peritoneal carcinomatosis should be considered in tumors at gastroesophageal junction

Medications

• Chemotherapy (cisplatin and fluorouracil) plus radiation therapy for patients with “curable” disease who are poor surgical candidates

• Combination chemotherapy may be considered in those patients with metastatic disease who still have good functional status and expected survival of at least several months

  • For patients with poor functional status, single-agent therapy with a fluoropyrimidine, a taxane, or irinotecan may be used

  • Trastuzumab may be added to standard regimens when patients have metastatic distal esophageal and gastroesophageal junction adenocarcinomas positive for amplification of the HER2 gene (approximately 15% of cases)

  • Ramucirumab demonstrated a survival advantage in patients with adenocarcinoma of the gastroesophageal junction after progression on first-line therapy when used both as monotherapy or in combination with paclitaxel

• As with all metastatic solid tumors, immunotherapy with pembrolizumab should be considered if the tumor is either microsatellite instability-high or has deficient mismatch repair protein expression (dMMR)

• For the remainder of metastatic esophageal cancers, a PD-1 or PD-L1 targeted agent should be considered in second-line or later setting

Surgery

• Accepted surgical techniques for stage Ib, II, IIIA, or IIIB include

  • En bloc transthoracic excision of the esophagus with extended lymph node dissection

  • Transhiatal esophagogastrectomy (entailing laparotomy with cervical anastomosis)

  • Minimally invasive esophagectomy techniques

• There is general consensus that at least a D1 lymphadenectomy should be performed

• However, whether the D2 lymphadenectomy typically performed in higher-incidence countries (eg, Japan and South Korea) is superior to the D1 lymphadenectomy more commonly performed in the lower-incidence countries (eg, United States) is debated

• The optimal number of lymph nodes to be removed after neoadjuvant therapy is not known although a similar lymphadenectomy is recommended by expert guidelines

• The preferred neoadjuvant chemotherapy regimen used with radiation is weekly carboplatin plus paclitaxel

• As an alternative, cisplatin plus 5-fluorouracil may be used along with radiation

• Perioperative chemotherapy without radiation may also be considered for tumors of the gastroesophageal junction based on the randomized, multicenter, phase III MAGIC trial

Therapeutic Procedures

• Palliative therapy for patients with extensive local tumor spread (T4b) or distant metastases (M1), ie, most patients with stage IIIC and stage IV tumors

  • Radiation therapy

  • Peroral placement of expandable permanent wire stents

• Complications of stents occur in 20–40% and include perforation, migration, and tumor ingrowth

Complications

• Invasion of mediastinal structures

• Tracheoesophageal fistula

Prognosis

• Overall 5-year survival rate is < 20%

• Apart from distant metastasis (M1b), the two most important predictors of poor survival are adjacent mediastinal spread (T4) and lymph node involvement

• Whereas cure may be achieved in patients with regional lymph node involvement (stages IIB and III), involvement of nodes outside the chest (M1a) is indicative of metastatic disease (stage IV) that is incurable

• Palliative care is essential for patients whose disease progresses despite chemotherapy

Prevention

• Adenocarcinoma

  • Endoscopic surveillance every 3–5 years in patients with Barrett esophagus to detect dysplasia, carcinoma

• Squamous cell carcinoma

  • Eliminate cigarette smoking

  • In endemic regions, endoscopic screening may be warranted

When to Refer

• Patients should be referred to a gastroenterologist for evaluation and staging (endoscopy with biopsy, endoscopic ultrasound) and palliative endoscopic antitumor therapy (stent)

• Patients with curable and resectable disease for whom neoadjuvant therapy may be appropriate (stage IIB or IIIA) should be referred to medical, radiation, and surgical oncologists for consideration of neoadjuvant chemotherapy, chemoradiotherapy, or surgical resection

• Patients with metastatic disease should be referred to medical and radiation oncologists for consideration of palliative chemotherapy or chemoradiation

• Patients with metastatic disease and obstructive tumors not amenable to or refractory to palliative radiation or stenting may require referral to an interventional radiologist, gastroenterologist, or surgeon for gastric or jejunal tube placement for liquid artificial nutrition

• Early referral to palliative care services may improve symptom management in patients with advanced or metastatic disease

When to Admit

• Patients with high-grade esophageal obstruction with inability to manage oral secretions

• Patients with acute complications, such as perforation, bleeding, aspiration, or fistula, also require admission