What is the recommended management approach for a gastroesophageal (GE) junction tumor?

Management of Gastroesophageal Junction Tumors

For patients with gastroesophageal (GE) junction tumors, the recommended management approach is perioperative chemotherapy or neoadjuvant chemoradiotherapy followed by surgical resection for resectable advanced disease, with specific treatment tailored based on tumor characteristics and staging. 1

Initial Evaluation and Staging

• Endoscopic assessment with biopsy is essential for definitive diagnosis
• Staging workup should include:
  • Contrast-enhanced CT scan of thorax, abdomen, and pelvis
  • Endoscopic ultrasound (EUS) for T and N staging
  • PET-CT to improve detection of involved lymph nodes or metastatic disease
  • Laparoscopy with peritoneal washings to exclude metastatic disease in locally advanced cases
• Biomarker testing: For unresectable cases, evaluate HER2, PD-L1 CPS, MSI, and claudin 18.2 expression prior to first-line chemotherapy 1

Management Algorithm Based on Disease Stage

Early Stage Disease (T1a)

• Endoscopic resection is considered curative if:
  • Tumor is intramucosal or has submucosal invasion <500 μm
  • Tumor diameter <3 cm
  • Negative resection margins
  • No lymphovascular invasion or poorly differentiated components 1

Locally Advanced Resectable Disease

• Preferred approach: Perioperative chemotherapy or neoadjuvant chemoradiotherapy 1

  • Perioperative chemotherapy options:
    • ECF (epirubicin, cisplatin, and fluorouracil) (category 1)
    • ECF modifications: epirubicin with oxaliplatin and fluorouracil/capecitabine
    • Fluorouracil and cisplatin (category 1) 1
  • Neoadjuvant chemoradiotherapy followed by surgery

• Surgical approach based on tumor location:

  • Lymph node dissection: Lower mediastinal and suprapancreatic lymph node stations should be dissected for tumors with 2-4 cm esophageal invasion 1
  • Minimally invasive approach: Thoracoscopic (robotic) esophagectomy is recommended when a transthoracic approach is indicated 1

Metastatic or Locally Advanced Unresectable Disease

• First-line therapy:

  • For HER2-positive tumors: Add trastuzumab to chemotherapy 1
  • For HER2-negative tumors: Use same chemotherapy regimens as established for gastric adenocarcinoma 1

• Second-line therapy:

  • Ramucirumab as a single agent or in combination with paclitaxel for disease progression on or after prior fluoropyrimidine- or platinum-containing chemotherapy 2

Special Considerations

Oligo-metastatic Disease

• Surgical resection after chemotherapy may be considered in carefully selected patients with oligo-metastases 1

Treatment Selection Considerations

• Two-drug cytotoxic regimens are preferred for advanced disease due to lower toxicity
• Three-drug regimens should be reserved for medically fit patients with good performance status
• Infusional fluorouracil and capecitabine may be used interchangeably
• Cisplatin and oxaliplatin may be used interchangeably depending on toxicity profile 1

Monitoring and Follow-up

• After completion of chemotherapy or chemoradiotherapy, monitor for long-term treatment-related complications 1
• Regular follow-up is necessary to monitor for recurrence, nutritional status, and treatment-related complications

Common Pitfalls and Caveats

• Histology matters: Treatment approaches for adenocarcinoma and squamous cell carcinoma may differ, with surgery being more essential for adenocarcinoma
• Lymph node dissection: Inadequate lymph node harvesting can lead to understaging and suboptimal treatment
• Performance status: Treatment intensity should be adjusted based on patient's performance status and comorbidities
• Biomarker testing: Failure to test for HER2 status may result in missed opportunities for targeted therapy in advanced disease

The management of GE junction tumors requires a multidisciplinary approach involving surgeons, medical oncologists, radiation oncologists, gastroenterologists, and radiologists to optimize outcomes and minimize treatment-related morbidity.