Gastric Cancer: Comprehensive Overview
Gastric cancer requires systematic evaluation through endoscopic biopsy for diagnosis, followed by CT thorax/abdomen/pelvis, endoscopic ultrasound, and staging laparoscopy with peritoneal washings for all stage IB-III disease, with surgical resection plus perioperative chemotherapy as the curative treatment for localized/locally advanced disease. 1, 2
Epidemiology
Incidence: Gastric cancer is the sixth most common cancer in Europe with ~140,000 new cases annually, and the fourth leading cause of cancer death with ~107,000 deaths per year 1. In the US, approximately 30,300 new cases and 10,780 deaths were estimated in 2025 3.
Demographics: Peak incidence occurs in the seventh decade of life, with males affected twice as frequently as females 1. The median age at diagnosis is 68 years 3.
Geographic variation: Highest rates occur in East Asia, South America, and Eastern Europe; lowest rates in the United States and Western Europe 1. Japan and Korea have implemented successful screening programs that improve survival 1, 3.
Risk factors: Male gender, cigarette smoking, Helicobacter pylori infection (associated with 90% of gastric body/antrum cancers), atrophic gastritis, partial gastrectomy, Ménétrier's disease, high salt intake, alcohol, and obesity 1, 3. A small percentage have genetic predisposition syndromes (hereditary non-polyposis colorectal cancer, familial adenomatous polyposis, hereditary diffuse gastric cancer, Peutz-Jeghers syndrome) requiring genetics referral 1.
Clinical Presentation
Symptomatic presentation: In the US, >90% of patients present with symptoms including weight loss, abdominal pain, dysphagia, dyspepsia, vomiting, and early satiety 1, 3.
Iron-deficiency anemia: Common presenting feature requiring evaluation 1.
Stage at presentation: Approximately 13% have localized disease (limited to stomach), 15-25% have locally advanced disease (regional lymph node spread), and 35-65% have metastatic disease 3.
Diagnostic Work-Up
Initial Investigations
Endoscopy with biopsy: Diagnosis must be made from gastroscopic or surgical biopsy reviewed by an experienced pathologist, with histology reported according to WHO criteria 1, 2.
Routine blood tests: Complete blood count to check for iron-deficiency anemia, liver and renal function tests to determine appropriate therapeutic options 1, 2.
Histologic classification: 90% are adenocarcinomas, subdivided into diffuse (undifferentiated) and intestinal (well-differentiated) types by Lauren classification 1, 2. This distinction impacts prognosis and treatment planning 2.
Biomarker testing: HER2 testing is mandatory for all cases if metastatic disease is documented or suspected, as it determines trastuzumab eligibility 2, 3.
Staging Investigations
CT thorax, abdomen ± pelvis: Contrast-enhanced CT is the primary staging modality for detecting local/distant lymphadenopathy and metastatic disease 1, 2.
Endoscopic ultrasound (EUS): Essential for determining proximal and distal tumor extent and provides accurate T and N stage assessment, though less useful for antral tumors 1, 2.
Staging laparoscopy with peritoneal washings: Recommended for all stage IB-III stomach cancers to detect occult peritoneal metastases that imaging frequently misses 1, 2, 4. This is particularly critical as it identifies 20-30% of patients with peritoneal disease not detected by imaging 2.
PET imaging: May improve staging through increased detection of involved lymph nodes/metastatic disease, but can be uninformative in mucinous tumors and diffuse histology (high false-negative rate) 1, 2, 4.
Staging Classification
TNM Staging (AJCC)
T1: Invades lamina propria or submucosa 2
T2: Invades muscularis propria or subserosa 2
T3: Penetrates serosa without invading adjacent structures 2
T4: Invades adjacent structures 2
N1: 1-6 regional lymph nodes 2
N2: 7-15 regional lymph nodes 2
N3: >15 regional lymph nodes 2
M0: No distant metastasis 2
M1: Distant metastasis present 2
Minimum lymph node harvest: At least 15 nodes must be examined for accurate N staging; inadequate evaluation leads to understaging 2, 4.
Treatment Options
Multidisciplinary Planning
- Mandatory team approach: Core membership must include surgeons, medical and radiation oncologists, gastroenterologists, radiologists, pathologists, dieticians, and nurse specialists 1, 2.
Surgical Treatment
Curative intent: Surgical resection is the only potentially curative treatment modality 1.
Early gastric cancer (T1a): May be amenable to endoscopic resection if well-differentiated, ≤2 cm, confined to mucosa, not ulcerated, and no lymphovascular invasion (lymph node metastatic risk virtually zero) 1.
Localized disease (stage I): Treated with surgical resection; 5-year relative survival rate is 75% with treatment 3.
Locally advanced disease (stage IB and above): Requires gastrectomy plus perioperative chemotherapy with 5-fluorouracil, oxaliplatin, and docetaxel, plus immunotherapy (durvalumab) 1, 3.
Systemic Therapy for Advanced Disease
Metastatic or unresectable disease: Treated with chemotherapy, immunotherapy, and/or targeted therapy depending on biomarkers (PD-L1, HER2, CLDN18.2) 3.
PD-L1-expressing tumors: Adding immune checkpoint inhibitors (nivolumab, pembrolizumab) provides an additional 3 months of survival compared to chemotherapy alone 3.
HER2-overexpressing tumors: Addition of trastuzumab provides an additional 3-4 months of survival 3.
CLDN18.2-expressing tumors: Addition of zolbetuximab provides an additional 3-4 months of survival 3.
Supportive Care
- Early integration: Early supportive care focusing on symptom management, nutritional support, and psychosocial support is associated with 3 months of survival benefit 3.
Prognosis
Stage-specific survival (5-year): Stage I: 50%; Stage II: 29%; Stage III: 13%; Stage IV: 3% 5.
Metastatic disease: Less than 10% of patients with metastatic gastric cancer survive more than 5 years 3.
Margin status: Pathologically clear margins yield 35% survival versus 13% with microscopically involved margins and 3% with grossly involved margins 5.
Critical Pitfalls to Avoid
Proceeding to surgery without laparoscopy: Misses 20-30% of patients with peritoneal disease in potentially resectable stage IB-III cases 2, 4.
Omitting HER2 testing in advanced disease: Delays targeted therapy initiation 2.
Inadequate lymph node harvest (<15 nodes): Results in stage migration and inaccurate prognostication 2, 4.
Relying on PET-CT for diffuse/signet ring histology: High false-negative rate makes CT and laparoscopy more reliable 2, 4.
Accepting microscopically involved margins: Associated with dramatically worse survival outcomes 5.