Diagnostic Confirmation in Advanced Gastric Cancer
For advanced gastric cancer, obtain tissue diagnosis via esophagogastroduodenoscopy (EGD) with multiple biopsies from the primary tumor site, followed immediately by comprehensive molecular testing for HER2, PD-L1, MSI/MMR, and CLDN18.2 status, as these biomarkers directly determine treatment eligibility and survival outcomes. 1
Tissue Diagnosis
Histopathologic confirmation is mandatory and must be obtained through gastroscopic or surgical biopsy, classified according to WHO criteria. 2
- Multiple biopsies from different gastric regions are essential—single-site biopsies are inadequate and may miss the diagnosis 1
- The tissue must provide sufficient material for both histologic classification and molecular biomarker analysis 3
- For early-stage disease suspected on imaging, endoscopic resection serves both diagnostic and therapeutic purposes and provides superior staging accuracy compared to simple biopsy 1
Mandatory Molecular Testing Panel
All patients with advanced gastric cancer require universal molecular testing at diagnosis, not after disease progression, as these results fundamentally alter treatment selection: 1
- HER2 testing (by immunohistochemistry or FISH) is required at diagnosis if advanced/metastatic disease is documented or suspected 1, 3
- MSI status (by PCR/NGS) or MMR status (by immunohistochemistry) must be performed in all newly diagnosed patients 1
- PD-L1 expression should be assessed if advanced/metastatic disease is present 1
- CLDN18.2 testing is recommended for advanced/metastatic disease 1
- Next-generation sequencing (NGS) should be considered via a validated assay to identify additional actionable mutations 1
The rationale is straightforward: HER2-positive patients are candidates for trastuzumab-based therapy, MSI-high/dMMR patients respond dramatically to immunotherapy, PD-L1 status guides checkpoint inhibitor use, and CLDN18.2 positivity opens targeted therapy options. 4, 5, 6
Staging Workup
Complete staging consists of: 2, 1
- Clinical examination focusing on lymph node regions, hepatosplenomegaly, and signs of metastatic disease (supraclavicular nodes, ascites, periumbilical nodules) 1
- Laboratory tests: complete blood count, comprehensive metabolic panel including liver and renal function tests 2, 1
- CT scan of chest, abdomen, and pelvis with oral and intravenous contrast to assess for metastatic disease 1, 3
- Endoscopic ultrasound (EUS) is preferred when early-stage disease is suspected or to differentiate early versus locally advanced disease 1
- FDG-PET/CT from skull base to mid-thigh for locally advanced or metastatic disease (but NOT for T1 disease, as it provides no benefit and represents unnecessary radiation exposure) 1
- Laparoscopy with or without peritoneal washings may help determine resectability and exclude occult peritoneal metastases not visible on CT 2, 7
Special Diagnostic Considerations
For esophagogastric junction tumors, Siewert classification must be documented as it determines whether the tumor is managed as esophageal or gastric cancer 1
H. pylori testing should be performed in all patients, with eradication therapy if positive, and testing of close family members is recommended 1
Common Diagnostic Pitfalls to Avoid
- Do not rely on single-site biopsies—inadequate sampling leads to false negatives 1
- Do not delay molecular testing until after first-line therapy fails—HER2, PD-L1, MSI, and CLDN18.2 status must be obtained at diagnosis to avoid missing critical treatment windows 1
- Do not order PET/CT for T1 disease—it adds cost and radiation without clinical benefit 1
- Do not skip laparoscopy in potentially resectable cases—CT misses peritoneal metastases in up to 30% of cases 7
- Do not accept fewer than 14 lymph nodes in surgical specimens—inadequate lymph node evaluation leads to understaging and suboptimal treatment planning 7