What are the staging, workup, and management options for a patient diagnosed with gastroesophageal junction (GEJ) adenocarcinoma?

Gastroesophageal Junction Adenocarcinoma: Staging, Workup, and Management

Initial Diagnosis and Workup

All patients with suspected GEJ adenocarcinoma require upper endoscopy with a minimum of six biopsies to establish histologic diagnosis and determine tumor location relative to the anatomic cardia (Siewert classification). 1, 2

Essential Baseline Studies

• Complete blood count, liver function tests, and renal function tests are mandatory to assess treatment eligibility and organ function 1, 2
• Upper endoscopy must document: tumor location, length, circumferential involvement, degree of obstruction, and distance from incisors 2
• Histologic confirmation per WHO criteria is required to distinguish adenocarcinoma from squamous cell carcinoma and small cell variants, as treatment differs fundamentally 1

Staging Algorithm

Step 1: Initial Imaging for Metastatic Disease

CT chest, abdomen, and pelvis with oral and IV contrast is the first-line staging modality to identify distant metastases. 1, 2

Step 2: Locoregional Staging (If No M1 Disease)

• Endoscopic ultrasound (EUS) with fine-needle aspiration should be performed to evaluate T and N stage, particularly for surgical planning 1
• PET-CT (not PET alone) should be added to CT and EUS for comprehensive staging, as it identifies occult distant metastases in approximately 15-20% of cases 1, 2

Step 3: Laparoscopy for Selected Cases

Staging laparoscopy is recommended for T3/T4 adenocarcinomas of the GEJ to rule out peritoneal metastases, which occur in 15-30% of locally advanced cases. 1, 2

Step 4: Biomarker Testing

HER2-neu testing must be performed if metastatic disease is documented or suspected, as it directly impacts systemic therapy selection. 2

Step 5: Nutritional and Performance Assessment

• Document ECOG or Karnofsky performance status to determine eligibility for aggressive multimodal therapy versus best supportive care 2
• Nutritional assessment with consideration of preoperative nutritional support (including jejunostomy if significant dysphagia) is essential 2

Management by Stage

Early Disease (Tis-T1a N0)

Surgery alone via endoscopic mucosal resection or esophagectomy is the treatment of choice for superficial tumors without nodal involvement. 1

• Endoscopic resection should be used for T1 tumors to define depth of invasion 1
• No neoadjuvant therapy is indicated for these early lesions 1

Localized Disease (T1b-T2 N0-1)

For resectable T1b-T2 tumors, the optimal approach remains debated between surgery alone versus neoadjuvant therapy followed by surgery. 1, 3

• Perioperative chemotherapy (pre- and postoperative) is supported by level I evidence for adenocarcinomas of the lower esophagus/GEJ 1
• Surgery should be performed at high-volume centers by surgeons performing at least 20 esophagogastric resections annually 1

Locally Advanced Disease (T3-T4 N0-1 M0)

Neoadjuvant chemoradiation followed by surgery is the preferred approach for locally advanced GEJ adenocarcinoma, as it increases R0 resection rates, improves local control, and provides survival benefit compared to surgery alone. 1

Neoadjuvant Regimen Options:

• Cisplatin/5-fluorouracil with concurrent radiotherapy (50 Gy in 25 fractions) is the most established regimen 1
• Alternative: Perioperative chemotherapy alone (without radiation) is also supported by level I evidence, though the comparative benefit of adding radiation remains unclear 1

Critical Caveat:

Preoperative chemoradiation may increase postoperative mortality, so careful patient selection is essential 1

Surgical Approach for Resectable Disease

For GEJ adenocarcinomas, transhiatal extended total gastrectomy or esophagogastrectomy is recommended for cardia, subcardia, and type II tumors. 1

• Adequate longitudinal and radial resection margins with appropriate lymphadenectomy (minimum 15 lymph nodes) must be achieved 1
• D2 lymphadenectomy should be performed in fit patients with clinical stage II-III disease 1
• The distal pancreas and spleen should not be routinely removed unless there is direct invasion 1

Metastatic Disease (M1)

For stage IV disease, systemic chemotherapy with HER2-targeted therapy (if HER2-positive) is the primary treatment, with surgery reserved only for palliation of obstruction or bleeding. 2

Common Pitfalls to Avoid

• Do not proceed to surgery without adequate staging: EUS and PET-CT frequently upstage disease and prevent futile operations 4
• Do not use preoperative radiation alone: It provides no survival benefit compared to surgery alone and is not recommended 1
• Do not perform limited gastric resections except for palliation or in very elderly patients, as they compromise oncologic outcomes 1
• Do not omit laparoscopy in T3/T4 tumors: Peritoneal metastases are missed by CT/PET in 15-30% of cases 1
• Do not forget nutritional support: Preoperative nutritional optimization reduces postoperative complications 2

Multidisciplinary Team Coordination

All patients must be discussed in an upper GI multidisciplinary tumor board before initiating treatment, with staging investigations coordinated within an agreed pathway. 1

• Surgery should only be performed at designated cancer centers with audited outcomes 1
• Individual surgeon and team outcomes must be benchmarked against national standards 1