What are the ESMO (European Society for Medical Oncology) guidelines for managing locally advanced gastroesophageal (GE) junction tumors?

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Last updated: August 26, 2025View editorial policy

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ESMO Guidelines for Management of Gastroesophageal Junction Tumors

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

Diagnosis and Staging

  • Endoscopic assessment with biopsy is essential for definitive diagnosis
  • Staging workup should include:
    • Contrast-enhanced CT scan
    • Endoscopic ultrasound
    • PET-CT
    • Laparoscopy with peritoneal washings for locally advanced cases

Surgical Approach

  • For GE junction tumors with 2-4 cm esophageal invasion, dissection of lower mediastinal and suprapancreatic lymph node stations is recommended 2
  • Similar lymph node dissection should be performed regardless of histological type (adenocarcinoma or squamous cell carcinoma) for cT2 or deeper tumors 2
  • Thoracoscopic (robotic) esophagectomy is preferred when a transthoracic approach is indicated 2
  • Adequate surgery requires:
    • Clear surgical margins
    • Appropriate nodal dissection
    • Goal of obtaining at least 16-18 (preferably 20) lymph nodes 1

Treatment Recommendations Based on Disease Status

Locally Advanced Resectable Disease

  1. Perioperative Chemotherapy:

    • FLOT regimen (docetaxel, oxaliplatin, leucovorin, and fluorouracil) is preferred
    • Consists of 4 preoperative and 4 postoperative 2-week cycles
    • Best for smaller tumors without significant proximal extension 1
    • Alternative regimens include cisplatin and fluorouracil
  2. Preoperative Chemoradiotherapy:

    • Preferred for large, bulky tumors with proximal extension where complete surgical resection is challenging 1
    • Tumor location, size, and risk of positive margins are important considerations
  3. Surgical Considerations:

    • Transthoracic approach with thoracoscopic (robotic) esophagectomy is recommended 2
    • The transhiatal approach with less extensive lymphadenectomy may favor chemoradiotherapy over perioperative chemotherapy 1

Unresectable or Inoperable Disease

  • Definitive chemoradiotherapy is recommended for patients ineligible for surgery 1
  • Preoperative chemotherapy alone should be considered for patients who cannot tolerate radiation 1

Oligometastatic Disease

  • Surgical resection after chemotherapy may be considered in carefully selected patients with oligometastases 2

Biomarker Testing

  • Biomarker testing is strongly recommended prior to first-line chemotherapy in unresectable cases 2
  • Essential biomarkers include:
    • HER2 expression
    • PD-L1 CPS (Combined Positive Score)
    • MSI (Microsatellite Instability)
    • Claudin 18.2 expression

Endoscopic Management

  • White light endoscopy (WLE) alone is recommended for detection of GE junction adenocarcinoma, except in high-risk patients such as those with Barrett's esophagus 2
  • For determining lateral extent of superficial neoplasia, additional modalities such as image-enhanced endoscopy (IEE) are recommended 2
  • Endoscopic resection may be considered curative for superficial neoplasia if:
    • Tumor is intramucosal carcinoma or has submucosal invasion <500 μm
    • Tumor diameter <3 cm
    • Negative resection margins
    • No lymphovascular invasion or poorly differentiated components 2

Advanced Disease Management

  • For unresectable advanced or recurrent GE junction adenocarcinoma, the same chemotherapy regimens as established for gastric adenocarcinoma should be used 2
  • For HER2-positive tumors, add trastuzumab to chemotherapy
  • Two-drug cytotoxic regimens are preferred due to lower toxicity; three-drug regimens should be reserved for medically fit patients with good performance status 1

Follow-up

  • Regular follow-up is necessary to monitor for recurrence, nutritional status, and treatment-related complications
  • Monitoring for long-term treatment-related complications is essential after completion of therapy

The management of GE junction tumors requires a multidisciplinary approach to optimize outcomes and minimize treatment-related morbidity. Treatment decisions should consider tumor location, histology, stage, and patient factors to determine the optimal therapeutic strategy.

References

Guideline

Multimodality Therapy for Gastroesophageal Junction Tumors

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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