What is the recommended staging workup and treatment approach for a patient with gastric cancer, considering their age, overall health status, medical history, including Helicobacter pylori (H. pylori) infection and family history of gastric cancer?

Gastric Cancer Staging Workup

All newly diagnosed gastric cancer patients require esophagogastroduodenoscopy with biopsy, contrast-enhanced CT of chest/abdomen/pelvis, complete blood count, comprehensive metabolic panel, and universal molecular testing for MSI/MMR status, with additional HER2, PD-L1, and CLDN18.2 testing if advanced/metastatic disease is suspected. 1

Essential Initial Workup Components

Clinical Assessment

• Complete history and physical examination focusing on dysphagia, weight loss, early satiety, vomiting, anemia symptoms, and bleeding 1
• Screen for family history of gastric cancer and hereditary cancer syndromes (hereditary diffuse gastric cancer, Lynch syndrome, familial adenomatous polyposis, Peutz-Jeghers syndrome) 1
• Document H. pylori infection status and eradicate if positive, particularly in early gastric cancer; recommend testing of close family members 1
• Assess nutritional status with formal nutritional counseling 1
• Provide smoking cessation advice, counseling, and pharmacotherapy as indicated 1

Imaging Studies

• Chest/abdomen/pelvis CT with oral and IV contrast is the primary staging modality for T, N, and M staging 1, 2, 3
• FDG-PET/CT (skull base to mid-thigh) for locally advanced or metastatic disease, or if clinically indicated 1
• Endoscopic ultrasound (EUS) is preferred if early-stage disease is suspected or to differentiate early versus locally advanced disease 1
• Endoscopic resection (ER) is essential for accurate staging of early-stage cancers (T1a or T1b), as early-stage cancers are best diagnosed by ER 1

Laboratory Testing

• CBC and comprehensive chemistry profile to assess for anemia, organ function, and metabolic abnormalities 1

Molecular and Biomarker Testing

Universal testing required for all patients:

• MSI by PCR/NGS or MMR by IHC in all newly diagnosed patients 1

Additional testing if advanced/metastatic disease documented or suspected:

• HER2 testing (intestinal-type tumors more likely HER2-positive) 1
• PD-L1 testing 1
• CLDN18.2 testing 1
• NGS should be considered via validated assay 1

Additional Staging Procedures

• Assess Siewert category for gastroesophageal junction tumors 1
• Biopsy of metastatic disease as clinically indicated 1
• Laparoscopy with or without peritoneal washings should be performed in all patients considered potentially resectable to exclude occult metastatic disease 1

Stage-Specific Considerations

Early-Stage Disease (T1a/T1b)

• EUS is the preferred modality for determining depth of invasion in early disease 1, 2
• Endoscopic resection provides the most accurate staging for T1 lesions and should be performed when feasible 1

Locally Advanced Disease

• FDG-PET/CT is recommended for locally advanced disease to detect occult metastases 1
• Laparoscopy is mandatory before proceeding with curative intent surgery to exclude peritoneal metastases 1

Metastatic Disease

• Biopsy confirmation of metastatic sites when clinically indicated 1
• Complete molecular profiling (HER2, PD-L1, CLDN18.2, MSI/MMR, NGS) to guide systemic therapy selection 1

Critical Pathology Requirements

Biopsy Specimens

• Multiple biopsies (5-8) should be obtained to provide adequate material for histologic and molecular interpretation 1
• Histologic classification as intestinal versus diffuse type has therapeutic implications 1

Surgical Specimens

• Minimum of 15-16 lymph nodes must be examined for adequate staging, with optimal recovery of at least 25 lymph nodes 1
• Pathology report must document: tumor location relative to esophagogastric junction, depth of invasion, lymphovascular invasion, margins, lymph node status, and number of nodes recovered 1

Common Pitfalls to Avoid

• Do not rely on CT alone for T staging in early disease—EUS is significantly more accurate for T1-T2 differentiation 1, 2, 3
• Do not skip laparoscopy in potentially resectable disease—it detects occult peritoneal metastases missed by CT in up to 30% of cases 1
• Do not proceed without molecular testing—MSI/MMR status is required for all patients, and HER2/PD-L1/CLDN18.2 testing is essential if advanced disease is present or suspected 1
• Do not accept inadequate lymph node sampling—fewer than 15 examined nodes compromises accurate staging 1
• Do not overlook H. pylori testing—eradication is recommended in early gastric cancer and reduces risk in family members 1

Age and Comorbidity Considerations

• Medical fitness assessment determines candidacy for major abdominal surgery and influences treatment approach 1
• Nutritional optimization is critical before any treatment, particularly in elderly patients with weight loss 1
• Performance status profoundly influences outcome and treatment selection 1