What labs should be ordered for a patient with newly diagnosed metastatic gastric adenocarcinoma?

Laboratory Tests for Newly Diagnosed Metastatic Gastric Adenocarcinoma

For patients with newly diagnosed metastatic gastric adenocarcinoma, essential laboratory tests include complete blood count (CBC), comprehensive chemistry profile, HER2 testing, MSI/MMR testing, and PD-L1 testing. 1

Core Laboratory Workup

Required Tests

• Complete Blood Count (CBC)

  • Evaluates for anemia, which is common in gastric cancer
  • Assesses white blood cell and platelet counts

• Comprehensive Chemistry Profile

  • Liver function tests (AST, ALT, alkaline phosphatase, bilirubin)
  • Renal function (BUN, creatinine)
  • Electrolytes
  • Albumin (nutritional status assessment)

Essential Biomarker Testing

• HER2 Testing

  • Method: Immunohistochemistry (IHC) with reflex to in situ hybridization (ISH) for equivocal (2+) results
  • Critical for determining eligibility for HER2-targeted therapies (trastuzumab, fam-trastuzumab deruxtecan)
  • HER2 positivity rates: 12-23% of gastric cancers, higher in intestinal subtype (19-33%) than diffuse subtype (6-8%) 1

• MSI/MMR Testing

  • Universal testing recommended for all newly diagnosed patients
  • Methods: PCR/NGS for MSI or IHC for MMR proteins (MLH1, MSH2, MSH6, PMS2)
  • Identifies candidates for immune checkpoint inhibitor therapy (pembrolizumab, dostarlimab-gxly) 1

• PD-L1 Testing

  • Combined Positive Score (CPS) assessment
  • Determines eligibility for first-line nivolumab with chemotherapy (CPS ≥5 is category 1 recommendation) 1

Additional Recommended Testing

• Next-Generation Sequencing (NGS)

  • May be considered via validated assay
  • Identifies actionable mutations:
    • NTRK gene fusions (for entrectinib/larotrectinib eligibility)
    • Tumor Mutational Burden (TMB) (for pembrolizumab eligibility if ≥10 mutations/megabase) 1

• Tumor Markers

  • CEA and CA 19-9
    • Not recommended for screening or early diagnosis due to inadequate sensitivity/specificity
    • Useful for monitoring treatment response and disease progression 2
    • Note: May show transient increases ("surges") during early effective chemotherapy, which should not be misinterpreted as disease progression 3

Clinical Pitfalls to Avoid

1. Incomplete biomarker testing: Failure to test for HER2, MSI/MMR, and PD-L1 may result in missed opportunities for targeted therapies that can significantly improve survival outcomes.

2. Misinterpreting tumor marker elevations: Initial rises in CEA or CA19-9 after starting chemotherapy may represent a "surge phenomenon" rather than disease progression. All patients with documented surges showed clinical benefits from chemotherapy in studies 3.

3. Relying solely on single biomarkers: Combined biomarker assessment provides better diagnostic and prognostic information than individual markers alone 4.

4. Delaying treatment for extensive testing: While comprehensive testing is important, essential tests (CBC, chemistry, HER2, MSI/MMR) should be prioritized to avoid delaying treatment initiation.

Implementation Algorithm

1. At diagnosis:

   • Order CBC and comprehensive chemistry profile
   • Ensure adequate tissue is obtained for biomarker testing
   • Request HER2, MSI/MMR, and PD-L1 testing on tumor specimen

2. Before starting systemic therapy:

   • Assess left ventricular ejection fraction (LVEF) if considering HER2-targeted therapy 5
   • Consider baseline tumor markers (CEA, CA 19-9) for future monitoring

3. Consider additional testing based on clinical scenario:

   • NGS if limited tissue is available or to identify additional treatment options
   • Circulating tumor DNA (ctDNA) testing in select cases for monitoring disease burden 6

By following this comprehensive laboratory testing approach, clinicians can optimize treatment selection and monitoring for patients with metastatic gastric adenocarcinoma, potentially improving outcomes and quality of life.