Gastric Cancer Workup
All patients with suspected gastric cancer require esophagogastroduodenoscopy (EGD) with biopsy as the cornerstone diagnostic test, followed by comprehensive staging with CT imaging and universal molecular testing for MSI/MMR, HER2, PD-L1, and CLDN18.2 if advanced disease is present. 1
Initial Diagnostic Evaluation
Essential Components
EGD with multiple biopsies from the primary tumor site is mandatory for histopathologic diagnosis according to WHO criteria 1
Complete blood count and comprehensive metabolic panel including liver and renal function tests 1
CT scan of chest, abdomen, and pelvis with oral and intravenous contrast to assess for metastatic disease 1
Physical examination focusing on lymph node regions, hepatosplenomegaly, and signs of metastatic disease 1
Advanced Staging Studies
FDG-PET/CT from skull base to mid-thigh is recommended for locally advanced or metastatic disease, though not appropriate for T1 disease 1
Endoscopic ultrasound (EUS) is preferred when 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) and may be both diagnostic and therapeutic 1
Laparoscopy may help optimally determine resectability in selected cases 1
Molecular and Biomarker Testing
Universal Testing (All Patients)
- Microsatellite instability (MSI) by PCR/NGS or mismatch repair (MMR) by immunohistochemistry should be performed in all newly diagnosed patients 1
Advanced/Metastatic Disease Testing
HER2 testing is required at diagnosis if advanced/metastatic disease is documented or suspected 1
PD-L1 testing should be performed if advanced/metastatic disease is documented or suspected 1
CLDN18.2 testing is recommended if advanced/metastatic disease is documented or suspected 1
Next-generation sequencing (NGS) should be considered via a validated assay 1
Special Considerations
Esophagogastric Junction Tumors
- Siewert tumor type classification must be assessed in all patients with EGJ adenocarcinoma 1
H. pylori Assessment
Test for H. pylori infection and eradicate in all patients with early gastric cancer if positive 1
Recommend H. pylori testing of close family members in positive cases 1
Additional Assessments
Nutritional assessment and counseling should be performed in all patients 1
Screen for family history of gastric cancers 1
Smoking cessation advice, counseling, and pharmacotherapy as indicated 1
Common Pitfalls to Avoid
Do not rely on single-site biopsies during EGD—multiple biopsies from different gastric regions are essential for accurate diagnosis 1. The 2025 NCCN guidelines emphasize that early-stage cancers are best diagnosed by endoscopic resection rather than simple biopsy alone 1.
Do not skip molecular testing in advanced disease—HER2, PD-L1, and CLDN18.2 status directly impact treatment options and should be obtained at diagnosis rather than waiting for disease progression 1.
Do not perform PET/CT for T1 disease—this represents unnecessary radiation exposure and cost without clinical benefit 1.