What is the recommended approach to diagnosing and treating tumors at the gastro‑oesophageal (GE) junction?

Approach to Gastroesophageal Junction Tumors

The management of GE-junction tumors requires a stage-specific algorithmic approach: superficial lesions meeting strict criteria undergo endoscopic resection, locally advanced resectable disease receives perioperative FLOT chemotherapy (or neoadjuvant chemoradiotherapy as an alternative), and unresectable/metastatic disease mandates comprehensive biomarker testing (HER2, PD-L1 CPS, MSI, claudin 18.2) before initiating systemic therapy. 1, 2

Initial Diagnostic Workup

Endoscopic Evaluation

• Use white light endoscopy (WLE) alone for initial tumor detection, except in high-risk patients with Barrett's esophagus who should receive image-enhanced endoscopy (IEE) 1
• Add IEE to WLE for determining lateral tumor extent to ensure accurate margin assessment 1
• Document precise tumor location relative to the GE junction and measure esophageal invasion length

Staging Considerations

Perform diagnostic laparoscopy with peritoneal washings in patients with:

• Signet ring cell histology, OR
• Tumor extending ≥2 cm beyond the GE junction with ≥T3 disease 2

This identifies occult peritoneal metastases (risk increases from 7.5% at 2 cm to 35% at 4 cm beyond GEJ with signet ring features). Include both subphrenic and pelvic lavage for maximum sensitivity 2.

Treatment Algorithm by Stage

Superficial/Early Disease (Endoscopic Candidates)

Endoscopic resection is curative when ALL criteria are met 1:

• Intramucosal carcinoma OR submucosal invasion <500 μm depth
• Tumor diameter <3 cm
• Negative resection margins
• No lymphovascular invasion
• No poorly differentiated components

Critical pitfall: Any deviation from these strict criteria mandates surgical resection due to lymph node metastasis risk.

Locally Advanced Resectable Disease

Perioperative FLOT chemotherapy (fluorouracil, leucovorin, oxaliplatin, docetaxel) is the preferred neoadjuvant approach for locally advanced GEJ adenocarcinoma 2, 3. The FLOT4 and ESOPEC trials established FLOT's superiority over older regimens and demonstrated better overall survival compared to chemoradiotherapy alone.

Alternative acceptable approach: Neoadjuvant chemoradiotherapy (carboplatin/paclitaxel with radiation) followed by surgery 1, 2. The CROSS regimen showed improved pathologic complete response rates and local control.

For Eastern practice patterns: Upfront surgery followed by adjuvant chemotherapy remains acceptable, particularly for patients where perioperative therapy compliance is uncertain 1.

Surgical Approach Specifics

For tumors with 2-4 cm esophageal invasion:

• Dissect lower mediastinal AND suprapancreatic lymph node stations 1
• Use similar lymph node dissection extent regardless of histology (adenocarcinoma vs. squamous cell carcinoma) for cT2 or deeper tumors 1

When transthoracic approach is indicated:

• Thoracoscopic or robotic esophagectomy is preferred over open esophagectomy 1
• This applies to both adenocarcinoma and squamous cell carcinoma

For cT2N0 disease: Esophagectomy is recommended, with neoadjuvant therapy decision based on lymph node involvement risk through shared decision-making 2.

Oligometastatic Disease

Surgical resection after chemotherapy is appropriate in carefully selected patients with oligometastases 1. This represents a paradigm shift from historical nihilism about metastatic disease, though patient selection criteria must be stringent.

Unresectable/Metastatic Disease

MANDATORY biomarker testing before first-line therapy 1:

• HER2 expression status (strongly recommended)
• PD-L1 Combined Positive Score (CPS) (strongly recommended)
• Microsatellite instability (MSI) (strongly recommended)
• Claudin 18.2 expression (strongly recommended)

This is the only strong recommendation in the 2024 guidelines, reflecting the critical importance of precision medicine in advanced disease 1.

Chemotherapy regimens: Use the same protocols established for unresectable gastric adenocarcinoma (e.g., FLOT, FOLFOX, or other platinum/fluoropyrimidine combinations) 1.

Key Clinical Nuances

Histology Considerations

The guidelines recommend treating GEJ adenocarcinoma and esophageal adenocarcinoma similarly, using gastric cancer chemotherapy regimens for advanced disease 1. This reflects the biological continuum of these tumors.

Common Pitfalls to Avoid

1. Inadequate endoscopic assessment: Failing to use IEE for margin determination leads to incomplete resections
2. Skipping laparoscopy in high-risk patients: Missing peritoneal disease upstages 7-46% of patients depending on risk factors 2
3. Omitting biomarker testing in metastatic disease: This eliminates targeted therapy options that significantly improve outcomes
4. Insufficient lymphadenectomy: Inadequate nodal dissection for tumors with 2-4 cm esophageal invasion compromises oncologic outcomes

Evidence Quality Context

Most recommendations carry "weak" strength due to heterogeneity in trial populations and treatment approaches between Eastern and Western centers 1. The only strong recommendation is comprehensive biomarker testing in unresectable disease, reflecting robust evidence for precision oncology 1. The 2025 AATS guidelines and 2026 ESOPEC data provide the most contemporary evidence favoring FLOT over older regimens 2, 3.