What is the recommended treatment approach for a locally advanced gastroesophageal (GE) junction tumor?

Treatment Approach for Locally Advanced Gastroesophageal Junction Tumors

Multimodality therapy is strongly recommended for patients with locally advanced gastroesophageal (GE) junction tumors, with either preoperative chemoradiotherapy or perioperative chemotherapy as the preferred approaches. 1

Initial Assessment and Staging

• Complete staging workup should include:
  • Contrast-enhanced CT scan
  • Endoscopic ultrasound
  • PET-CT
  • Laparoscopy with peritoneal washings for locally advanced cases 2
• Biomarker testing is essential for unresectable cases:
  • HER2, PD-L1 CPS, MSI, and claudin 18.2 expression 1, 2

Treatment Algorithm for Locally Advanced GE Junction Adenocarcinoma

First-Line Treatment Options:

1. Perioperative Chemotherapy

   • FLOT regimen (preferred): 4 preoperative and 4 postoperative 2-week cycles of:
     • Docetaxel 50 mg/m²
     • Oxaliplatin 85 mg/m²
     • Leucovorin 200 mg/m²
     • Fluorouracil 2,600 mg/m² as 24-hour infusion on day 1 1, 3
   • Alternative if FLOT not feasible: Cisplatin and fluorouracil 1
   • Best for: Smaller tumors at GE junction without significant proximal extension 1

2. Preoperative Chemoradiotherapy

   • Followed by surgery
   • Best for: Large bulky tumors with proximal extension where complete surgical resection is challenging 1
   • Provides higher R0 resection rates compared to perioperative chemotherapy 4

Decision Factors for Treatment Selection:

• Tumor characteristics:

  • Location: For tumors with significant proximal extension, preoperative chemoradiotherapy is preferred 1
  • Size: Larger, bulkier tumors benefit more from chemoradiotherapy 1
  • Risk of positive margins: Higher risk favors chemoradiotherapy 1

• Surgical approach considerations:

  • With transhiatal approach (less extensive lymphadenectomy), chemoradiotherapy is preferred over perioperative chemotherapy 1
  • For transthoracic approach, thoracoscopic (robotic) esophagectomy is recommended 1

Evidence Supporting Treatment Recommendations

The FLOT4 trial demonstrated superior outcomes with perioperative FLOT compared to ECF/ECX regimens:

• Median overall survival: 50 months vs. 35 months (HR 0.77; 95% CI 0.63-0.94) 3
• Comparable toxicity profiles between regimens 3

A retrospective comparison of preoperative chemoradiation vs. perioperative chemotherapy showed:

• Trend toward improved overall survival with chemoradiation (41.7 vs. 21.0 months) 4
• Higher R0 resection rates with chemoradiation (100% vs. 76.9%, P=0.05) 4
• More pathological complete remissions with chemoradiation 4

Special Considerations

• For patients ineligible for surgery: Definitive chemoradiotherapy is recommended 1
• For patients who cannot tolerate radiation: Preoperative chemotherapy alone should be considered 1
• For advanced/metastatic disease: Ramucirumab is indicated (as single agent or with paclitaxel) for patients with disease progression after fluoropyrimidine or platinum-containing chemotherapy 5

Surgical Principles

• Adequate surgery requires:
  • Clear surgical margins
  • Appropriate nodal dissection (abdominal and thoracic)
  • Goal of obtaining at least 16-18 (preferably 20) lymph nodes 1
• Lymph node dissection should include lower mediastinal and suprapancreatic stations for tumors with 2-4 cm esophageal invasion 2

Common Pitfalls to Avoid

1. Inadequate staging: Leads to inappropriate treatment selection and poor outcomes
2. Underestimating the extent of disease: May result in positive margins if preoperative therapy is not optimized
3. Delaying surgery after neoadjuvant therapy: Surgery should be performed within 4-6 weeks after completion of preoperative treatment 6
4. Overlooking the importance of biomarker testing: Essential for guiding treatment in advanced disease 1, 2

The evidence strongly supports multimodality therapy for locally advanced GE junction tumors, with treatment selection guided by tumor characteristics and surgical approach considerations.