What is the recommended staging workup and treatment approach for a patient with gastric adenocarcinoma?

Gastric Adenocarcinoma Staging

All patients with gastric adenocarcinoma require a comprehensive staging workup consisting of physical examination, complete blood count, liver and renal function tests, upper endoscopy with biopsy, CT scan of thorax/abdomen/pelvis, endoscopic ultrasound, and staging laparoscopy with peritoneal washings for all potentially resectable cases. 1

Mandatory Initial Staging Components

Laboratory and Clinical Assessment

• Complete blood count with differential is required as part of the baseline workup 1
• Comprehensive metabolic panel including liver function tests (AST, ALT, alkaline phosphatase, bilirubin) and renal function (creatinine, BUN) must be obtained 2, 1
• Physical examination should document performance status, palpable masses, hepatomegaly, ascites, and supraclavicular lymphadenopathy 2, 1

Tissue Diagnosis

• Gastroscopic biopsy reviewed by an experienced pathologist is mandatory, with histology reported according to WHO criteria 2
• Histologic classification into diffuse (undifferentiated) versus intestinal (well-differentiated) types directly impacts prognosis and treatment planning 1

Cross-Sectional Imaging

CT Scanning

• Contrast-enhanced CT of thorax, abdomen, and pelvis is the primary staging modality and must be performed in all patients 2, 1
• CT provides simultaneous assessment of T-stage, regional lymph node involvement, and distant metastases 1
• Use oral and intravenous contrast for optimal visualization 1

Endoscopic Ultrasound (EUS)

• EUS is essential for determining proximal and distal tumor extent and accurate T-stage, particularly in early gastric cancers 2, 1
• EUS has 86% sensitivity for distinguishing T1/2 from T3/4 disease 3
• Limitation: EUS is less useful in antral tumors and stenotic lesions 2

Staging Laparoscopy

Diagnostic laparoscopy with or without peritoneal washings is mandatory for all patients with stage IB-III disease considered potentially resectable to exclude occult peritoneal metastases that CT frequently misses 2, 3, 1. This is particularly critical because:

• Laparoscopy detects occult peritoneal disease in 20-30% of patients deemed resectable by CT alone 1
• The diagnostic accuracy of laparoscopy for determining resectability is 98.6%, sparing over 40% of patients unnecessary laparotomies 4
• Signet ring cell carcinoma has higher propensity for peritoneal dissemination that CT underdetects 3

PET Imaging Considerations

PET-CT should be reserved for select cases and avoided as primary staging in diffuse/signet ring histology due to high false-negative rates 3, 1. Specifically:

• PET may upstage patients with gastric cancer but can be falsely negative in mucinous and diffuse tumor types 2
• Use PET-CT only when there is no evident M1 disease on CT and additional staging information would change management 1

TNM Staging Classification

Stage according to the AJCC/UICC TNM system 2, 3, 1:

T Stage (Depth of Invasion)

• T1: Invades lamina propria or submucosa 1
• T2: Invades muscularis propria or subserosa 2, 1
• T3: Penetrates serosa without invading adjacent structures 2, 1
• T4: Invades adjacent structures (spleen, transverse colon, liver, diaphragm, pancreas, abdominal wall, adrenal gland, kidney, small intestine, retroperitoneum) 2, 1

N Stage (Regional Lymph Nodes)

• N0: No regional lymph node metastasis 2, 1
• N1: Metastasis in 1-6 regional lymph nodes 2, 1
• N2: Metastasis in 7-15 regional lymph nodes 2, 1
• N3: Metastasis in >15 regional lymph nodes 2, 1

M Stage (Distant Metastasis)

• M0: No distant metastasis 1
• M1: Distant metastasis present 1

Biomarker Testing

HER2 testing by immunohistochemistry is mandatory for all gastric and gastroesophageal junction adenocarcinomas to determine eligibility for trastuzumab-based therapy in metastatic disease 3, 5. Key points:

• Use FDA-approved tests specifically validated for gastric cancers, not breast cancer assays 5
• Gastric cancers show incomplete membrane staining and more frequent heterogeneous HER2 expression compared to breast cancers 5
• HER2-positive metastatic gastric cancer is treated with trastuzumab in combination with cisplatin and capecitabine or 5-fluorouracil 5

Multidisciplinary Planning

Multidisciplinary treatment planning is mandatory before initiating therapy, comprising surgeons, medical and radiation oncologists, gastroenterologists, radiologists, and pathologists 2, 1, 6.

Critical Staging Pitfalls to Avoid

• Never proceed to surgery without laparoscopy in potentially resectable stage IB-III disease—imaging misses peritoneal metastases in 20-30% of cases 3, 1, 6
• Do not rely on PET scanning for staging signet ring cell or diffuse-type carcinoma—the mucinous nature produces false-negative results 3, 1
• Do not accept lymph node evaluation with <15 nodes examined—this leads to systematic understaging and inaccurate prognostication 3, 1
• Do not omit HER2 testing in advanced disease—this delays targeted therapy initiation 1
• Do not use suboptimally fixed tissue or deviate from assay instructions for HER2 testing—this leads to unreliable results 5