Stomach Cancer (Gastric Cancer)

Types of Stomach Cancer

Adenocarcinoma (90-95%)

Cancers that develop from the glandular cells lining the stomach. Two main classifications:

Lauren Classification (histologic types):

• Intestinal type (50-60%)
  • Well-differentiated, gland-forming
  • More common in older patients, men
  • Associated with H. pylori, intestinal metaplasia
  • Better prognosis than diffuse type
  • Declining incidence
• Diffuse type (30-40%)
  • Poorly differentiated, individual cells infiltrate stomach wall
  • Includes signet ring cells
  • More common in younger patients, women
  • Can cause "linitis plastica" (leather bottle stomach)
  • Generally worse prognosis
  • Incidence stable or increasing
• Mixed type (10-15%) - features of both

Location in Stomach:

• Cardia (gastroesophageal junction, upper stomach) - 30-40%, increasing in Western countries
• Body/fundus (middle/upper stomach) - 20-30%
• Antrum/pylorus (lower stomach) - 30-40%, decreasing

Other Stomach Cancers (5-10%)

• Lymphoma - primarily MALT lymphoma (mucosa-associated lymphoid tissue)
  • Often associated with H. pylori infection
  • May respond to H. pylori eradication alone (early stage)
• Gastrointestinal stromal tumor (GIST) - starts in specialized cells in stomach wall
  • Treated differently than adenocarcinoma
  • Responds to targeted therapy (imatinib)
• Neuroendocrine tumors (carcinoid) - rare, from hormone-producing cells

Risk Factors

Helicobacter pylori (H. pylori) Infection

• Most important modifiable risk factor
• Increases risk 2-6 fold
• Causes chronic gastritis → atrophic gastritis → intestinal metaplasia → dysplasia → cancer
• Present in ~50% of world population (higher in developing countries)
• WHO classified as Group 1 carcinogen
• Eradication reduces but doesn't eliminate cancer risk

Dietary Factors

• High-risk foods:
  • Smoked, salted, and pickled foods
  • Processed meats (nitrates/nitrites)
  • High salt intake
• Protective foods:
  • Fresh fruits and vegetables (especially citrus)
  • Foods high in vitamin C and carotenoids

Smoking and Alcohol

• Smoking increases risk ~2-fold (especially cardia cancers)
• Heavy alcohol use increases risk

Medical Conditions

• Pernicious anemia - autoimmune condition causing B12 deficiency, atrophic gastritis
• Previous stomach surgery - partial gastrectomy (especially >15 years prior)
• Gastric polyps - adenomatous polyps can become cancerous
• Ménétrier disease - overgrowth of stomach lining
• Chronic atrophic gastritis
• Intestinal metaplasia - precancerous change

Genetic/Hereditary Factors

• Family history - 2-3 times higher risk if first-degree relative affected
• Hereditary diffuse gastric cancer (HDGC)
  • CDH1 gene mutation (~1-3% of gastric cancers)
  • Very high lifetime risk (70-80% for men, 50-60% for women by age 80)
  • Prophylactic gastrectomy recommended for carriers
• Lynch syndrome (hereditary colorectal cancer syndrome) - also increases gastric cancer risk
• Familial adenomatous polyposis (FAP)
• Blood type A - slightly increased risk (20% higher)

Geographic and Demographic Factors

• Geography - highest rates in East Asia (Japan, Korea, China), Eastern Europe, Central/South America
• Age - median age at diagnosis ~68 years, uncommon before age 40
• Sex - 2 times more common in men
• Ethnicity - higher in Asian, Hispanic, Black populations in the US

Signs and Symptoms

Early stomach cancer usually causes no symptoms. Most patients are diagnosed with advanced disease in countries without screening programs.

Early Symptoms (Often Vague)

• Indigestion or heartburn - persistent, not relieved by antacids
• Loss of appetite
• Mild nausea
• Feeling full after small meals (early satiety)
• Vague abdominal discomfort

Later Symptoms (More Advanced Disease)

• Unintentional weight loss
• Abdominal pain - often upper abdomen
• Vomiting - especially if tumor causes obstruction
• Blood in stool - may appear black/tarry (melena) or cause anemia
• Vomiting blood (hematemesis)
• Difficulty swallowing (dysphagia) - if tumor near gastroesophageal junction
• Abdominal swelling - from ascites (fluid) or large tumor
• Weakness and fatigue - from anemia
• Jaundice - if cancer spreads to liver

Diagnosis

Upper Endoscopy (EGD)

• Gold standard for diagnosis
• Flexible camera inserted through mouth to visualize stomach lining
• Biopsies taken of suspicious areas (at least 6-8 samples)
• Can assess tumor location, size, appearance
• Usually done with sedation (outpatient procedure)

Biopsy Analysis

• Confirms cancer diagnosis
• Determines type (intestinal vs diffuse)
• Grade (how abnormal cells look)
• HER2 testing - critical for treatment planning
  • HER2-positive in 10-20% of gastric/GEJ cancers
  • Predicts response to trastuzumab (Herceptin)
• PD-L1 testing - for immunotherapy eligibility
• Microsatellite instability (MSI) testing - found in ~5-10%

Staging Tests

• CT scan of chest, abdomen, pelvis - looks for spread to lymph nodes, liver, lungs
• Endoscopic ultrasound (EUS) - determines depth of tumor invasion, nearby lymph nodes
  • Most accurate for T and N staging
  • Important for determining if surgery is possible
• PET/CT scan - may be used to detect distant metastases
• Laparoscopy - sometimes done before planned surgery
  • Detects small peritoneal metastases missed on imaging (10-20% of cases)
  • Prevents unnecessary major surgery

Blood Tests

• Complete blood count (CBC) - check for anemia
• Liver and kidney function tests
• Tumor markers (CEA, CA 19-9) - not diagnostic but may be useful for monitoring

Staging

Stomach cancer is staged using the TNM system (AJCC 8th Edition):

T (Tumor Depth)

• Tis - Carcinoma in situ (high-grade dysplasia, not invasive)
• T1 - Invades lamina propria or submucosa (early cancer)
• T2 - Invades muscularis propria
• T3 - Penetrates subserosal tissue
• T4 - Invades serosa (T4a) or adjacent structures (T4b)

N (Lymph Nodes)

• N0 - No regional lymph node metastasis
• N1 - 1-2 regional lymph nodes
• N2 - 3-6 regional lymph nodes
• N3 - 7+ regional lymph nodes (N3a: 7-15, N3b: 16+)

M (Metastasis)

• M0 - No distant metastasis
• M1 - Distant metastasis (liver, peritoneum, distant lymph nodes, lungs)

Stage Grouping and Survival

Treatment Options

Treatment depends on stage, location, HER2 status, and patient factors. A multidisciplinary team (surgeon, medical oncologist, radiation oncologist) is essential.

Localized/Locally Advanced Disease (Stages I-III)

Surgery (Gastrectomy)

Mainstay of curative treatment:

• Subtotal gastrectomy - removes part of stomach (for lower stomach tumors)
  • Remaining stomach connected to small intestine
  • Preserves some normal stomach function
• Total gastrectomy - removes entire stomach (for upper/middle stomach or diffuse tumors)
  • Esophagus connected directly to small intestine
  • Requires permanent dietary adjustments
• Lymph node dissection (lymphadenectomy)
  • D1: nearby lymph nodes removed
  • D2: more extensive lymph node removal (standard in experienced centers)
  • At least 15 lymph nodes should be examined for accurate staging

Surgical considerations:

• Major operation, typically 3-5 hour surgery
• Hospital stay 7-10 days
• Best outcomes at high-volume centers (>15-20 gastrectomies/year)
• Laparoscopic (minimally invasive) approach increasingly used at experienced centers

Perioperative Chemotherapy

Standard approach for locally advanced disease (T2+, any N+):

• Chemotherapy before AND after surgery improves survival
• FLOT regimen (preferred):
  • 5-FU, Leucovorin, Oxaliplatin, Docetaxel
  • 4 cycles before surgery + 4 cycles after (8 total)
  • 5-year survival ~45% vs ~35% with older regimens
• Alternative regimens:
  • ECF/EOX (Epirubicin, Cisplatin/Oxaliplatin, 5-FU/Capecitabine)
  • 3 cycles before + 3 cycles after surgery
• Benefits of preoperative chemotherapy:
  • Shrinks tumor (may make surgery easier, improve resection rates)
  • Treats micrometastases early
  • Tests tumor response to chemotherapy

Adjuvant Chemoradiation (Alternative Approach)

• More common in the US (especially if no preoperative chemotherapy given)
• Chemotherapy + radiation therapy after surgery
• Used if inadequate lymph node dissection or positive margins

Early Gastric Cancer (Stage IA, T1)

• Endoscopic resection may be possible for very early tumors
  • Endoscopic mucosal resection (EMR)
  • Endoscopic submucosal dissection (ESD) - more widely used in Japan/Korea
  • Avoids major surgery in select patients
  • Strict criteria: small (<2cm), well-differentiated, no lymphovascular invasion

Metastatic Disease (Stage IV)

Goal is to extend survival and maintain quality of life. Not curable, but many patients live 1-2+ years with treatment.

First-Line Chemotherapy

HER2-Positive Tumors (10-20%):

• Trastuzumab + Chemotherapy (standard)
  • Trastuzumab (Herceptin) - monoclonal antibody targeting HER2
  • Plus chemotherapy: fluoropyrimidine (5-FU or capecitabine) + platinum (cisplatin or oxaliplatin)
  • Median survival ~16 months (vs 11 months without trastuzumab)
  • Continued until disease progression
• Pembrolizumab + Trastuzumab + Chemo
  • Adding pembrolizumab (checkpoint inhibitor) improves outcomes further
  • Especially if PD-L1 positive

HER2-Negative Tumors:

• Chemotherapy doublet or triplet:
  • Fluoropyrimidine (5-FU, capecitabine) + platinum (cisplatin, oxaliplatin)
  • Can add docetaxel (DCF regimen) for fit patients (more toxic but more effective)
• Immunotherapy combination (if PD-L1 positive or MSI-high):
  • Nivolumab + chemotherapy (CheckMate-649 trial)
  • Pembrolizumab + chemotherapy
  • Improved survival vs chemotherapy alone

Second-Line and Beyond

• Ramucirumab (Cyramza) - anti-VEGF antibody
  • Alone or with paclitaxel chemotherapy
  • Standard second-line option
  • Median survival ~9 months
• Immunotherapy (for MSI-high or high TMB tumors, ~5-10%)
  • Pembrolizumab or nivolumab
  • Can have dramatic, durable responses in select patients
• Trifluridine/tipiracil (Lonsurf) or irinotecan - later-line options
• Fam-trastuzumab deruxtecan (Enhertu) - newer HER2-targeted antibody-drug conjugate
  • For HER2-positive disease after trastuzumab
  • Impressive response rates (~50%)
• Claudin18.2-targeted therapy (zolbetuximab) - emerging option for claudin-positive tumors

Palliative Procedures

• Stent placement - for obstruction (difficulty swallowing/eating)
• Feeding tube (J-tube) - if unable to eat adequately
• Palliative radiation - for bleeding, pain, or obstruction
• Palliative surgery - rarely, to relieve obstruction or severe bleeding

Life After Gastrectomy

Eating and Nutrition

Major adjustments required, especially after total gastrectomy:

• Eat small, frequent meals (6-8 small meals/day instead of 3 large ones)
  • Stomach's reservoir function is lost
  • Can only handle small amounts at a time
• Eat slowly and chew thoroughly
• Avoid drinking with meals - drink 30-60 minutes before/after eating
  • Prevents dumping syndrome
  • Reduces feeling too full
• Focus on protein and calories - weight loss common after surgery
• Limit simple sugars - can cause dumping syndrome

Dumping Syndrome

Food moves too quickly from stomach (or esophagus) into small intestine:

• Early dumping (10-30 minutes after eating):
  • Nausea, cramping, diarrhea
  • Sweating, dizziness, rapid heartbeat
• Late dumping (1-3 hours after eating):
  • Weakness, shakiness, sweating
  • From rapid blood sugar spike then drop
• Prevention: eat small meals, limit simple sugars, separate liquids from solids
• Improves over time for most patients (6-12 months)

Vitamin and Nutrient Deficiencies

• Vitamin B12 deficiency (very common after total gastrectomy)
  • Stomach produces intrinsic factor needed for B12 absorption
  • Requires lifelong B12 injections (monthly) or high-dose oral supplements
• Iron deficiency - stomach acid aids iron absorption
  • May need iron supplements or infusions
  • Monitor for anemia
• Calcium and vitamin D - reduced absorption
  • Risk of osteoporosis
  • Require supplementation
• Regular blood tests to monitor vitamin levels

Weight Management

• Weight loss of 10-20% common after gastrectomy
• Work with dietitian to maximize calorie/protein intake
• May need nutritional supplements (Ensure, Boost, etc.)
• Weight usually stabilizes 6-12 months after surgery

Prevention and Screening

Prevention Strategies

• H. pylori eradication
  • Triple or quadruple therapy antibiotics (1-2 weeks)
  • Reduces gastric cancer risk by 30-50%
  • Most effective if treated before precancerous changes develop
• Dietary modifications
  • Eat more fresh fruits and vegetables
  • Limit smoked, salted, and pickled foods
  • Reduce processed meat consumption
• Don't smoke
• Limit alcohol
• Maintain healthy weight

Screening

• Japan and Korea - national screening programs (endoscopy or barium swallow)
  • High incidence justifies population screening
  • Detects many early-stage cancers
  • Contributed to improved survival rates
• United States - no routine screening (lower incidence)
  • Consider endoscopy for high-risk individuals:
    • Asian ethnicity (especially immigrants from high-risk countries)
    • Strong family history (especially if diffuse type or young age)
    • Hereditary diffuse gastric cancer syndrome (CDH1 mutation carriers)
    • Lynch syndrome
    • Advanced precancerous changes (dysplasia, extensive intestinal metaplasia)

Genetic Testing and Prophylactic Surgery

• Consider genetic counseling if:
  • Diffuse gastric cancer at young age (<40 years)
  • Multiple family members with gastric cancer (especially diffuse type)
  • Personal or family history of lobular breast cancer + gastric cancer
• CDH1 mutation carriers:
  • 70-80% lifetime risk of gastric cancer (men), 50-60% (women)
  • Prophylactic total gastrectomy recommended (typically age 20-30)
  • Also increased risk of lobular breast cancer in women

Current Research

• Immunotherapy combinations - optimizing checkpoint inhibitor use in first-line treatment
• Novel targeted therapies - FGFR, Claudin18.2, HER2-targeted ADCs
• Perioperative immunotherapy - adding immunotherapy to FLOT regimen
• Circulating tumor DNA (ctDNA) - liquid biopsy for early detection, monitoring minimal residual disease
• Molecular subtyping - personalizing treatment based on tumor genomics (TCGA classification)
• Optimizing HER2-targeted therapy - sequencing strategies, combination approaches
• CAR-T and cellular therapies - early-phase trials

Frequently Asked Questions

What causes stomach cancer?

Most cases result from a combination of factors. H. pylori infection is the most important risk factor, causing chronic inflammation that can lead to precancerous changes over decades. Diet (high salt, smoked foods), smoking, and genetic factors also play roles. In developed countries, the decline in H. pylori infection and improved food preservation (refrigeration replacing salting/smoking) have led to decreasing rates.

Is stomach cancer curable?

Yes, if detected early. Stage IA stomach cancer has 70-95% 5-year survival with surgery. Unfortunately, most cases in Western countries are diagnosed at advanced stages (III-IV) where cure rates are much lower (15-30% for stage III, 5-10% for stage IV). This is why screening in high-risk populations is so important.

Can I live without a stomach?

Yes, though it requires significant lifestyle adjustments. After total gastrectomy, the esophagus is connected directly to the small intestine. You'll need to eat small, frequent meals (6-8 per day), take vitamin B12 injections for life, and possibly other supplements. Most people adapt well over time and maintain good quality of life, though initial adjustment can be challenging.

What is HER2 and why does it matter?

HER2 is a protein that promotes cell growth. About 10-20% of gastric/GEJ cancers have too much HER2 (HER2-positive). This is important because trastuzumab (Herceptin), a drug that targets HER2, significantly improves survival when added to chemotherapy (median survival ~16 months vs ~11 months). All newly diagnosed advanced gastric cancers should be tested for HER2.

Should I be screened for stomach cancer?

In the US, routine screening is not recommended for average-risk individuals due to low incidence. However, consider discussing screening with your doctor if you: have a strong family history (multiple relatives with gastric cancer), are Asian and over age 50-60 (especially if from high-incidence country), have hereditary cancer syndrome (Lynch, FAP), have CDH1 mutation, or have advanced precancerous changes (dysplasia).

How is stomach cancer different from colon cancer?

While both are gastrointestinal adenocarcinomas, they're treated quite differently. Stomach cancer often requires perioperative chemotherapy (before and after surgery), while colon cancer typically gets surgery first, then adjuvant chemotherapy. Stomach cancer has different molecular targets (HER2 is important, MSI less common). Surgical approaches differ significantly. Stomach cancer has generally worse prognosis for similar stages.

What is FLOT chemotherapy?

FLOT is the preferred perioperative chemotherapy regimen for resectable gastric cancer: 5-FU (fluorouracil), Leucovorin (enhances 5-FU), Oxaliplatin (platinum), and Docetaxel (taxane). You receive 4 cycles before surgery (to shrink the tumor) and 4 cycles after surgery (to kill any remaining cancer cells). The FLOT4 trial showed superior survival compared to older regimens.

Will chemotherapy cure my advanced stomach cancer?

Unfortunately, metastatic (stage IV) stomach cancer is not curable with current treatments. However, chemotherapy (often with targeted therapy like trastuzumab for HER2+ or immunotherapy) can significantly extend survival and improve quality of life. Median survival with modern treatment is 12-19+ months, with some patients living 2-3+ years. Treatment goals are to shrink tumors, control symptoms, and maximize quality time.

What is signet ring cell carcinoma?

Signet ring cell carcinoma is a subtype of diffuse gastric cancer where cancer cells have a characteristic appearance under the microscope (mucin-filled cells pushing the nucleus to one side, looking like a signet ring). It tends to be more aggressive, affects younger patients more often, and has worse prognosis than intestinal-type gastric cancer. It can cause "linitis plastica" (rigid, thickened stomach wall).

Can stomach cancer be prevented?

While not all cases can be prevented, risk can be significantly reduced. H. pylori eradication reduces risk by 30-50%. Dietary changes (more fresh fruits/vegetables, less smoked/salted foods) help. Not smoking and limiting alcohol also reduce risk. In very high-risk genetic cases (CDH1 mutation), prophylactic gastrectomy prevents cancer but is a major decision requiring careful counseling.

What happens during follow-up after treatment?

After curative treatment, you'll have regular visits (every 3-4 months for first 2 years, then every 6 months for years 3-5, then annually). Each visit includes physical exam, blood tests (CBC, chemistry, possibly tumor markers), and assessment for symptoms. CT scans are done periodically (every 6-12 months). Endoscopy may be done if concerning symptoms develop. You'll also need monitoring for nutritional deficiencies (especially B12, iron).