Gastric Cancer

See Also

Epidemiology

Incidence (2020)
1. Worldwide: 1 million cases/year (4th most common malignancy)
  1. Asia (esp. east asia): 16.1 cases per 100,000 people (two thirds of cases in world)
  2. Africa: 4 cases per 100,000 people
2. United States: 27,000 cases/year (16th most common malignancy)
  1. Incidence: 4.1 per 100,000 people
3. Overall Incidence has decreased in the last 100 years
  1. May be related to reduced Helicobacter Pylori colonization and improved sanitation
Ethnicity
1. Incidence in non-hispanic caucasians is 50% of people of color (Asian, Hispanic, Black, Native american)
Gender
1. More common in men by 2:1 ratio
Age
1. Onset: 40 to 70 years
2. Uncommon to rare in age <45 years (1 in 100,000 people)
Heredity
1. Family History contributes to 10% overall (syndromes account for 3% of cases)
2. See Risk Factors below

Pathophysiology

Adenocarcinoma accounts for 95% of cases
Atrophic Gastritis precedes metaplasia and malignancy

Risk Factors
General

Helicobacter Pylori (distal Stomach tumors, RR 2.5)
Pernicious Anemia (RR 2.2)
Obesity (RR 1.9, gastric cardia)
Tobacco Abuse (RR 1.6)
High salt diet
Gastric adenoma
Gastroesophageal Reflux (gastric cardia)
Hiatal Hernia (gastric cardia)
Barrett's Esophagus (gastric cardiac and esophageal border)
Prior subtotal gastrectomy (after 15-20 years)
Chronic atrophic Gastritis
Racial predisposition (twice as common as caucasians)
1. Native americans
2. Hispanic
3. Black
4. Asian

Risk Factors
Hereditary Syndromes

First degree relative with Gastric Cancer confers 2.7 increased Relative Risk
Primary heritable syndromes associated with Gastric Cancer
1. Hereditary Diffuse Gastric Cancer
2. Gastric Adenocarcinoma and Proximal Polyposis of the Stomach
3. Familial Intestinal Gastric Cancer
Other associated hereditary syndromes
1. Lynch Syndrome
2. Familial Adenomatous Polyposis
3. Li-Fraumeni Syndrome
4. Peutz-Jeghers Syndrome
5. Non-polyposis hereditary Colon Cancer

Symptoms

Asymptomatic in early stages in 80% of cases
Late stage symptoms (typical presentation)
1. Weight loss (62% of patients)
2. Abdominal Pain or Dyspepsia (52% of patients)
3. Nausea
4. Dysphagia
5. Melana
6. Early satiety

Signs

Epigastric tenderness or fullness is variably present
Hepatomegaly
Lymphadenopathy (e.g. periumbilical or supraclavicular)
Other uncommon presentations
1. Gastrocolic fistula
2. Colonic obstruction
3. Paraneoplastic Syndrome

Differential Diagnosis

Diagnostics

Upper endoscopy (Esophogastroduodenoscopy or EGD)
1. Best tool for Gastric Cancer diagnosis
2. Sydney system recommends 5 to 8 biopsies
Endoscopic Ultrasonography (EUS)
1. Used to stage Gastric Cancer
Other Testing
1. Double contrast barium swallow
  1. Largely replaced by the widespread availability of upper endoscopy
  2. Historically had been used as a cost effective, invasive initial evaluation
  3. Could be considered in low resource regions

Evaluation
Screening

Routine screening (e.g. pepsinogen, EGD) in the general U.S. population has no evidence to support
Screening may be indicated in some Hereditary Syndromes
1. Consider genetic screening
Endoscopy Screening in high Incidence regions (e.g. east asia) may decrease mortality
1. Zhang (2018) Gastroenterology 155(2):347-54 +PMID: 29723507 [PubMed]

Evaluation
Diagnostic

Indications for upper endoscopy
1. Dyspepsia and weight loss (esp. age >55 years)
2. Dyspepsia with Nausea and Vomiting (esp. repeated Vomiting)
3. Dyspepsia resistant to treatment (e.g. >2-3 months)
4. Dysphagia (Difficult Swallowing)
5. Upper Gastrointestinal Bleeding
6. Imaging findings (e.g. CT Abdomen) suggestive of Gastric Cancer
7. Symptoms with suspicious lab findings (e.g. Thrombocytosis)
Protocol
1. Upper endoscopy with 5 to 8 biopsies
Interpretation: No Dysplasia
1. Benign or low risk chronic atrophic Gastritis
  1. No surveillance needed
2. High Risk chronic atrophic Gastritis
  1. Upper endoscopy repeated 3 times in first year to re-evaluate for lesions
Interpretation: Chronic Atrophic Gastritis with Dysplasia
1. Lesion not visible on endoscopy
  1. High grade dysplasia: Repeat endoscopy with multiple biopsies every 6 months
  2. Low grade dysplasia: Repeat endoscopy with multiple biopsies every 12 months
2. Lesion visible on endoscopy and <=1 cm diameter
  1. Mucosal resection under endoscopy
  2. Repeat endoscopy yearly
3. Lesion visible on endoscopy and >1 cm diameter
  1. Submucosal dissection under endoscopy
  2. Repeat endoscopy yearly
Interpretation: Gastric Cancer
1. Imaging and Diagnostics
  1. CT chest, Abdomen and Pelvis with oral and IV contrast
  2. Fluorodeoxyglucose-PET Scan
  3. Endoscopic Ultrasound
    1. Differentiates superficial from advanced primary malignancies
2. Labs
  1. Comprehensive Metabolic Panel
  2. Complete Blood Count
  3. Tumor Markers and Genetic Testing
  4. Biopsy suspected metastases

Staging
TNM Classification

Staging system
1. Primary Tumor (T)
  1. TX: Cannot assess
  2. Tis: Carcinoma in situ
  3. T0 - T4: Increasing degrees of local tumor invasion
2. Regional Lymph Nodes (N)
  1. NX: Cannot assess
  2. N0 - N3: Increasing degrees of Lymph Nodes involved
3. Distant metastases (M)
  1. MX: Cannot assess
  2. M0: No metastases
  3. M1: Distant metastases
Stages (Summary of AJCC Staging - not an exact list)
1. Stage 0: Tis, N0, M0 (Carcinoma in-situ)
2. Stage IA: T1, N0, M0 (Submucosa involved)
3. Stage IB: T1-T2b, N0-N1, MO (subserosa involved)
4. Stage II: T1-T3, N0-N2, M0 (visceral peritoneum)
5. Stage IIIA: T2a-T4a, N0-N2, M0 (local tumor invasion)
6. Stage IIIB: T3, N2, M0 (7-15 Lymph Nodes involved)
7. Stage IVA: T4b, N any, M0
8. Stage IVB: T any, N any, M1

Management

General
1. Most patients (80%) are diagnosed at a late stage of Gastric Carcinoma
2. Only 40% of Gastric Cancer patients are appropriate for curative therapy at time of presentation
3. Treatment is by a multidisciplinary team including medical, surgical and Radiation Oncology
4. All Gastric Cancer patients are tested for Helicobacter Pylori (and treated if positive)
  1. Reduces risk of invasive Gastric Cancer
Treatment is based on Staging (TNM Classification) and patient specific factors (esp. comorbidities)
1. Stage 0 (carcinoma in-situ)
  1. Endoscopic mucosal resection OR
  2. Gastrectomy with lymphadenectomy
2. Stage 1
  1. Treatment as in Stage 0 AND
  2. Perioperative Chemotherapy, followed by postoperative chemoradiation
3. Stage 2-3
  1. Partial or total gastrectomy with regional lymphadenectomy
  2. Perioperative Chemotherapy, followed by postoperative adjuvant chemoradiation
4. Stage 4
  1. Palliative Chemotherapy with or without Immunotherapy
  2. Palliative therapy goals
    1. Decrease pain (e.g. relieve Ascites with Paracentesis or peritoneal catheter)
    2. Relieve gastric obstruction (e.g. stenting)
    3. Treat Upper Gastrointestinal Bleeding (e.g. endoscopic clipping or ablation)
    4. Manage Malnutrition
Surveillance
1. Chronic Atrophic Gastritis with Dysplasia
  1. See diagnostics as above
  2. Repeat endoscopy yearly after endoscopic resection (every 6 months if lesion not visualized)
2. Stage 1
  1. Clinical follow up
3. Stage 2 to 3
  1. CT Chest, Abdomen and Pelvis with oral and IV contrast
    1. First 2 years: Every 6 to 12 months
    2. Years 3 to 5: Every 12 months
4. Nutritional deficiency monitoring after partial or total gastrectomy
  1. Vitamin B12 Deficiency
  2. Iron Deficiency
  3. Thiamine deficiency
  4. Zinc Deficiency
  5. Folate Deficiency
  6. Hypocalcemia
  7. Fat Soluble Vitamin Deficiency
    1. Vitamin A Deficiency
    2. Vitamin D Deficiency
    3. Vitamin E Deficiency
    4. Vitamin K Deficiency
Modalities
1. Radiation Therapy
  1. Moderately effective as adjunctive node positive or surgical margin positive cancer
  2. Postoperative Indications (in combination with Chemotherapy)
    1. Node positive Gastric Cancer without adequate lymphadenectomy
    2. Positive tumor surgical margins
2. Chemotherapy
  1. Indications
    1. Not effective as sole therapy (used as an adjunct to surgery and radiation)
    2. Localized Gastric Cancer (Stage >=N1 or >=T2)
      1. Perioperative Chemotherapy is strongly recommended by NCCN
    3. Advanced Gastric Cancer (unresectable, recurrent or metastatic)
      1. Chemotherapy extends survival by 6 months (if no prior Chemotherapy or radiation)
      2. Dual agent Chemotherapy may extend survival 1 month (but with greater toxicity)
  2. Chemotherapeutic agents used in Gastric Cancer
    1. Pyrimidine Analogs (Capecitabine, Fluorouracil)
    2. Platinum Analog Chemotherapeutic Agent (e.g. Carboplatin, Cisplatin)
    3. Taxanes (e.g. paclitazel, Docetaxel)
    4. Topoisomerase Inhibitor (e.g. Irinotecan)
  3. Biologic Agents used in Gastric Cancer
    1. Checkpoint Inhibitor (e.g. Pembrolizumab, Nivolumab, Ipilimumab)
    2. Anti-HER2 Monoclonal Antibody (e.g. Trastuzumab)
    3. VEGFR Monoclonal Antibody (e.g. Ramucirumab)
3. Surgery
  1. Gastric resection is based on tumor location in Stomach
    1. Early Gastric Cancers <2 cm, no ulceration, and low risk for lymph spread
      1. Endoscopic Resection
    2. Cancer of proximal-third of Stomach
      1. Gastrectomy with distal Esophagus resected
    3. Cancer of middle-third of Stomach
      1. Total gastrectomy
    4. Cancer of distal-third of Stomach
      1. Intestinal adenocarcinoma: Subtotal gastrectomy
      2. Diffuse carcinoma: Total Gastrectomy
  2. Lymph Node resection
    1. Adjacent Lymph Nodes are resected completely (except if distant metastases or vascular invasion)
    2. Regional node sampling (15 or more) for locally advanced gastric Gastric Cancers

Prognosis

Five year survival
1. Stage O (Carcinoma In Situ): 90%
2. Stage I (Localized Cancer): 75 to 78%
3. Stage II (Regional Cancer): 34%
4. Stage III: <20%
5. Stage IV (Distant Cancer Spread): 7%
Other factors with worse prognosis
1. Cardia region Gastric Cancers

Prevention

Tobacco Cessation
Dietary changes (possible benefit)
1. Decrease Alcohol intake
2. Decrease smoked, pickled or salted food intake
3. Increase fruit and vegetable intake
4. Consider Mediterranean Diet
Aggressively treat and monitor associated conditions
1. Barrett's Esophagus
2. Atrophic Gastritis
3. Helicobacter Pylori infection
  1. Ford (2020) Cochrane Database Syst Rev 7(7):CD005583 +PMID: 32628791 [PubMed]
Screening EGD for high risk patients every 1-3 years
1. See Risk factors above

References

Gunderson in Abeloff (2000) Oncology, p. 1545-79
Toh in Feldman (2002) Sleisenger GI, p. 829-47
Mott (2025) Am Fam Physician 111(2): 140-5
Layke (2004) Am Fam Physician 69(5):1133-40 [PubMed]