Esophageal and Esophagogastric Junction Cancer

Background

• The most common histological subtypes of esophageal and esophagogastric junction cancer are squamous cell carcinoma and adenocarcinoma.
• Esophageal and esophagogastric junction cancer is the seventh most common cancer worldwide, with annual age-standardized incidence 9.3 per 100,000 male persons per year, and 3.6 per 100,000 female persons per year in 2020.
• Adults > 50 years old and male persons are most commonly affected.
• Squamous cell carcinoma is more common in Asia, Eastern Europe, and sub-Saharan Africa, while adenocarcinoma is more common in North America and Western Europe.
• Most important risk factors for squamous cell carcinoma are tobacco smoking, and alcohol use, while the most important risk factors for adenocarcinoma are obesity, Barrett esophagus, gastroesophageal reflux disease (GERD), and high fat intake.
• Esophageal and esophagogastric gastric cancer is generally associated with poor prognosis, and represents the sixth leading cause of cancer mortality in the world, with annual age-standardized mortality 5.6 per 100,000 persons per year in 2020.

Evaluation

• Symptoms typically include new dysphagia, weight loss, appetite loss, symptoms suggestive of gastrointestinal bleeding, recurrent aspiration, emesis, and persistent heartburn.
• Consider all evaluations with multidisciplinary involvement (Weak recommendation)
• Consider diagnostic confirmation with histopathological analysis of upper gastrointestinal endoscopy-guided biopsy with immunohistochemical testing in poorly or undifferentiated cancers if distinguishing squamous cell carcinoma and adenocarcinoma is challenging (Weak recommendation)
• Consider initial staging evaluation and risk assessment with chest plus abdominal (with or without pelvic) oral and IV contrast-enhanced computed tomography (CT) (Weak recommendation), and blood tests
• For patients planning definitive resection, consider additional staging evaluations to rule out distant metastases otherwise undetected, including positron emission tomography/CT (PET/CT), endoscopic ultrasound, and/or bronchoscopy (for disease at or above carina) (Weak recommendation)
• For patients with suspected metastatic disease, consider molecular and biomarker testing, including microsatellite testing, PD-L1 testing, HER2 testing (for adenocarcinoma), and next-generation sequencing (Weak recommendation).

Management

Management of Locoregional Disease

• Consider preoperative nutritional support with enteric feeding tube (Weak recommendation).
• For patients with pTis or pT1a disease, or pT1b, N0 squamous cell carcinoma or superficial adenocarcinoma only, consider endoscopic management as the preferred management option (Weak recommendation).
• For patients with pTis-pT1b disease, cT1b-cT4a, any cN disease:
  • If surgical management is tolerable, consider esophagectomy (Weak recommendation).
    • For patients with cT2, N0 disease that is poorly differentiated or ≥ 3 cm, or involves lymphovascular invasion, cT1b-cT2, cN+ disease, or cT3-cT4a disease, consider either neoadjuvant chemoradiation (regardless of histology), or neoadjuvant plus adjuvant chemotherapy (perioperative chemotherapy) (for adenocarcinoma only), in conjunction with esophagectomy (Weak recommendation).
    • Adjuvant therapy considerations:
      • For patients with R1-R2 resection who have not received neoadjuvant chemoradiation, consider adjuvant fluoropyrimidine-based chemoradiation (Weak recommendation).
      • For patients with adenocarcinoma and high-risk pT2 after R0 resection who have not received neoadjuvant chemoradiation or neoadjuvant chemotherapy, consider adjuvant fluoropyrimidine-based chemoradiation (Weak recommendation).
      • For patients with adenocarcinoma and pT3-pT4a, or pN1 disease after R0 resection who have not received neoadjuvant chemoradiation or neoadjuvant chemotherapy, consider either adjuvant fluoropyrimidine-based chemoradiation or adjuvant systemic therapy (Weak recommendation).
      • For patients with R0 resection, and ypT1-4 and/or ypN1-3 disease after neoadjuvant chemoradiation, offer adjuvant nivolumab (Strong recommendation).
      • For patients with adenocarcinoma and R0 resection after neoadjuvant chemotherapy, continue adjuvant chemotherapy after esophagectomy as part of perioperative chemotherapy (Strong recommendation).
  • If surgical management is not tolerable or patient refusal, perform definitive chemoradiation (Strong recommendation).
  • If neither surgical management or chemoradiation is tolerable or feasible, consider palliative radiation therapy or best supportive care (Weak recommendation)
• For patients with cT4b disease:
  • Consider endoluminal stenting when appropriate.
  • Consider definitive chemoradiation, if it is tolerable (Weak recommendation).
  • If chemoradiation is not tolerable, consider either palliative radiation therapy or best supportive care (Weak recommendation).
  • If there is disease invasion of trachea, great vessels, vertebral body, or heart, consider systemic therapy alone (Weak recommendation).
• For patients with Siewert type III esophagogastric junction adenocarcinoma, consider management according to gastric adenocarcinoma.

Management of Unresectable Locally Advanced or Metastatic Disease

• Offer early referral to palliative care and nutritional support (Strong recommendation).
• For patients with good performance status and health, consider palliative management with systemic therapy and/or best supportive care (Weak recommendation).
  • Systemic therapy for patients with HER2-negative squamous cell carcinoma or adenocarcinoma:
    • Especially if PD-L1 expression is positive, first-line therapy generally involves nivolumab or pembrolizumab in combination with chemotherapy with fluoropyrimidine plus platinum (Strong recommendation).
    • For patients with squamous cell carcinoma, especially if PD-L1 expression is positive, nivolumab plus ipilimumab is an additional option (Weak recommendation).
    • If PD-L1 expression is low or negative, first-line therapy generally involves chemotherapy with fluoropyrimidine plus platinum (Weak recommendation).
  • For patients HER2-positive adenocarcinoma, first-line therapy generally involves trastuzumab in combination with chemotherapy with fluoropyrimidine plus platinum, with or without pembrolizumab (Strong recommendation).
• For patients with poor performance status and health, consider best supportive care only (Weak recommendation).