Stomach Cancer

Stomach cancer was the sixth commonest cancer in Hong Kong in 2022. It accounted for 3.6% of all new cancer cases. There were 1,272 new cases of stomach cancer in 2022. 720 patients were male and 552 were female. The male-female ratio of stomach cancer incidence was 1.3 : 1. The crude incidence rate was 17.3 per 100,000 standard population. Most of the stomach cancer patients were diagnosed at an older age. 864 of these new patients were over the age of 65.

Stomach cancer was the sixth leading cause of cancer deaths in Hong Kong. In 2022, it claimed 634 deaths, accounting for 4.3% of all cancer deaths. 

The stomach 

• The stomach is a muscular organ which lies between the lower end of the gullet (oesophagus) and the beginning of the bowel (intestine)
• Once food has been swallowed, it passes down the gullet and into the stomach. Glands in the wall of the stomach secrete substances which help break down the food, so that it leaves the content in the stomach in a semisolid form.
• The stomach also produces a substance that helps to absorb vitamin B12. This is important for the development of red blood cells.
• The most common type of stomach cancer is adenocarcinoma. Other rare types of stomach cancer include lymphoma and GIST.

• Age 
  • Occurs most commonly in people older than 55
  • Most patients are diagnosed with stomach cancer in their 60s and 70s
• Gender 
  • The risks for stomach cancer in men are 1.5 times that of women
• Helicobacter pylori (H.pylori) infection
  • A common bacterium called Helicobacter pylori, also called H. pylori, causes stomach inflammation and ulcers. It is also considered one of the main causes of stomach cancer. 
  • Testing for H. pylori is easily done, and a course of antibiotics can effectively eradicate the bacteria.
  • Testing for H. pylori is recommended if one has had a first-degree relative, such as parent, sibling, or child, who has been diagnosed with stomach cancer or an H. pylori infection. 
• Family history/ genetics
  • People who have parents, children or siblings with stomach cancer are at higher risks
  • Certain inherited genetic conditions can also increase risks, such as:
    • Hereditary diffuse gastric cancer
    • Lynch syndrome
    • Hereditary breast and ovary cancer (HBOC)
    • Familial adenomatous polyposis (FAP)
• Race/ethnicity
  • Stomach cancer is more common in Japan, China, South America and Eastern Europe. It is not as common in North America. 
• Diet
  • A high sodium diet is associated with increased risk of stomach cancer.
  • Foods preserved by drying, smoking, salting or pickling should be consumed less frequently
• Previous surgery or health conditions
  • People with these prior health conditions are at higher risks:
    • Pernicious anaemia 
    • Achlorhydria
    • No hydrochloric acid in gastric juices
• Tobacco and alcohol
  • Chronic, habitual tobacco use, and alcohol consumption greatly increase stomach cancer risks.
• Obesity

The signs or symptoms of stomach cancer include:

• Persistent indigestion
• Loss of appetite
• Weight loss
• A bloated feeling after eating
• Vomiting, (including blood)
• Blood in the stools (bowel motion) or black stools
• Swelling of the lower abdomen
• Anaemia, fatigue and weakness

However, these symptoms are similar to other diseases of the stomach, e.g. gastritis (inflammation of the stomach) or stomach or duodenal ulcer. If the above symptoms appear, a consultation with the doctor is recommended as soon as possible.

The following tests are commonly used to diagnose stomach cancer.

Getting the diagnosis

• Upper endoscopy (Oesophago-gastro-duodenoscopy, OGD) 
  • An upper gastrointestinal (GI) endoscopy is an examination of the upper gastro-intestinal tract, including the oesophagus, stomach and upper part of the small intestine (duodenum). The endoscope is a flexible tube with a light and lens that allows the doctor to look inside these organs.
  • An upper GI endoscopy is done to take samples of tissue to confirm the presence of and the type of cancer cells. 
• Endoscopic ultrasound (EUS):
  • Endoscopic ultrasound (EUS) uses an endoscope with an ultrasound probe at the end. It can provide detailed information about the location, size and depth of the tumour (how far it has spread into the wall of the stomach) and if cancer has spread to lymph nodes or surrounding tissues. EUS is often done simultaneously with an upper endoscopy.

Further investigations

• CT or PET-CT:
  • Used to confirm the location of the cancer and check if cancer has spread to other tissues and organs, such as the lymph nodes or liver
  • Sometimes, stomach cancer with peritoneal metastasis may not be well shown on PET-CT.  
• Laparoscopy
  • A laparoscopy is a minor surgery in which the surgeon inserts a thin, lighted, flexible tube called a laparoscope into the abdominal cavity. It is used to determine if cancer has spread to the lining of the abdominal cavity or liver. A CT or PET scan cannot often find cancer that has spread to these areas.

• Stage I
  • Stage IA: The cancer is contained within the inner lining of the stomach (mucosa) only. 
  • Stage IB: The cancer has spread either to the intermediate layer of the stomach (muscle layer), or is within the mucosa but affecting up to 2 of the nearby lymph nodes. 
• Stage II
  • Stage IIA: The cancer is within the mucosa but affecting 3-6 lymph nodes, or has spread into the muscle layer and 1-2 lymph nodes, or to the outer layer of the stomach (serosa) but not affecting any lymph nodes. 
  • Stage IIB: The cancer is within the mucosa but affecting between 7 and 15 lymph nodes, or is affecting the muscle layer and 3-6 lymph nodes, or has spread to within the serosa and 1-2 lymph nodes, or has spread beyond the serosa but not into any lymph nodes. 
• Stage III
  • Stage IIIA: The cancer has spread to the muscle layer and between 7 and 15 lymph nodes, or is within the serosa and is affecting 3-6 lymph nodes, or has spread beyond the serosa including 1-2 lymph nodes. 
  • Stage IIIB: The cancer is within the serosa and affecting between 7 and 15 lymph nodes, or beyond the serosa and affecting 3-6 lymph nodes, or through all three stomach layers and invading nearby organs and structures involving any number of lymph nodes. 
• Stage IV
  • The cancer has spread to organs close to the stomach and to at least 1 lymph node, or to more than 15 lymph nodes, or it has spread to other parts of the body such as the lungs. This is known as secondary cancer or metastatic cancer.

The doctor will consider the following for treatment of gastric cancer:

• Stages of the cancer
• Location of the tumour
• Programmed death-ligand (PD-L1) expression and tumour mutational burden (TMB) status
• Microsatellite instability (MSI) and mismatch repair mutation (MMR) status
• Presence of driver mutation e.g. HER2, Claudin 18.2
• General health condition

Surgery is often used to treat stomach cancer. The type of surgery depends mainly on the size and location of the tumour. Often during surgery, the lymph nodes close to the stomach are removed at the same time to see if cancer cells have spread into them.

The main types of surgery for treating stomach cancer include:

Endoscopic mucosal resection (EMR) or Endoscopic submucosal dissection (ESD)

• Endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) is a very specialised surgery for small (less than 2 cm), early-stage stomach cancer that has not spread beyond the inner lining of the stomach (called the mucosa). ESD is done using an endoscope placed through the mouth, throat and into the stomach. Saline is injected under the tumour to lift it away from the lining for easier extraction.
• The resected tumour is observed under microscope to see if the margin is clear of cancer cells. If there is close margin or residual disease, further surgery is usually required.

Gastrectomy: partial/ total gastrectomy

• A gastrectomy is the most common surgery to treat stomach cancer. A gastrectomy is the removal of all or part of the stomach and nearby lymph nodes. The oesophagus is reconnected to the small intestine. Sometimes other organs or structures like the spleen or omentum are also removed during gastrectomy.
• There are different types of gastrectomy. A total gastrectomy removes the whole stomach. A partial gastrectomy removes part of the stomach, either the upper (proximal) or lower (distal) half.

Lymph node dissection

• Since stomach cancer spreads to the surrounding lymph nodes easily, it is important to remove them to lower the chance of recurrence.
• In some East Asian countries, such as China, Japan, and South Korea, surgeons often remove a greater number of lymph nodes (at least 30) along the left gastric, common hepatic, celiac, and splenic arteries. 

Neoadjuvant/ Adjuvant treatment 

Chemotherapy

Chemotherapy for stomach cancer may be given as a single drug or as a combination of 2 or more drugs. The following are common chemotherapy drugs used before or after stomach surgery:

• Capecitabine and oxaliplatin
  • A regimen of two drugs: oral capecitabine and intravenous oxaliplatin. This regimen is usually given every 3 weeks for a total of 8 cycles.
  • This regimen may be considered before and after surgery.
• TS-ONE/ S-1
  • This is an oral medication that combines three pharmacological compounds:
    • Tegafur becomes 5-fluorouracil (5-FU) when metabolized. 5-FU can prevent the growth of cancer cells or result in cancer cell death.
    • Gimeracil inhibits 5-FU degradation, and sustains anti-tumour activity.
    • Oteracil Potassium reduces digestive side effects such as diarrhoea, while reducing toxicity associated with 5-FU.
  • TS-ONE is usually taken twice a day. In one cycle, the patient will continue to take TS-ONE for four weeks then rest for 2 weeks.
  • TS-ONE can be combined with docetaxel for Stage III stomach cancer as adjuvant treatment after operation. Adding docetaxel on top of TS-ONE can improve in overall survival and relapse-free survival in patients with Stage III gastric cancer.
• Patients with unresectable disease may receive chemoradiation with the following chemotherapy regimens:  
  • Capecitabine 
  • TS-ONE 
  • TS-ONE in combination with oxaliplatin, cisplatin or paclitaxel
• 5-FU, leucovorin, oxaliplatin and docetaxel (FLOT)
  • Some patients may have received chemotherapy before surgery to reduce the size of the tumour.
  • FLOT contains three chemotherapies (5FU, leucovorin, oxaliplatin and docetaxel) can be used. It is given every 2 weeks for four cycles before surgery then another 4 cycles after surgery.
• Common side effects of chemotherapy include:
  • Higher risk of infection
  • Anaemia
  • Malaise/ tiredness
  • Sore mouth/ mouth ulcers
  • Hair loss
  • Early menopause and fertility problems
  • Darkening of skin over face, fingers and hands
  • Kidney problem
  • Hand-foot syndrome

Radiotherapy

Radiation therapy uses high-energy X-rays or particles to disintegrate cancer cells. It is sometimes used together with chemotherapy (e.g. 5-FU) before or after surgery to reduce risks of recurrence.

The high dose radiation for treating stomach cancer may affect the surrounding organs, e.g. liver, bowels, kidneys, spinal cord and heart. Using CT scan for radiotherapy planning can help protect these surrounding organs.

Side effects from radiotherapy include:

• Fatigue/ malaise
• Weight loss
• Mild skin reaction
• Stomach discomfort
• Nausea and vomiting
• Loose bowel movements

When the stomach cancer is inoperable, the treatment intent would be palliative, i.e. to relieve symptoms and prevent complications.

The choice of treatment depends on tumour type (HER2-positive, HER2-negative, PD-L1 expression, MMR/MSI status), the patient’s health status as well as toxicity profiles of regimens.

Before deciding on a regimen, the doctor usually performs tests on the tumour to determine the cancer’s type and decide if any targeted therapy or immunotherapy can be used. Tests on the tumour include:

• HER2
• Claudin 18.2 
• PD-L1
• MMR/ MSI
• Epstein-Barr virus (EBV)

Treatment for advanced/ metastatic stomach cancer is mainly systemic anticancer treatment.

Chemotherapy

• Often used as first-line treatment for metastatic stomach cancer. 
• Combination regimens offer higher response rates and improved survival compared with single-agent therapy. Three-drug combinations are sometimes used but are more toxic with only minimal improvement in response.
• Although there is no standard first-line therapy, a fluoropyrimidine (e.g. 5-FU, capecitabine) and platinum doublet is typically the preferred backbone regimen for most patients.
• Commonly used chemotherapy for metastatic stomach cancer include:
  • Oxaliplatin/ Cisplatin/ Carboplatin
  • 5-FU: intravenous chemotherapy, or oral medications: capecitabine/ TS-ONE
  • Docetaxel/ paclitaxel
  • Irinotecan
  • Epirubicin

Targeted therapy

Trastuzumab

• Suitable for patients with HER2-positive advanced or metastatic stomach cancer (around 10-15%)
• Trastuzumab is added to first-line platinum-based chemotherapy (e.g. oxaliplatin, cisplatin or carboplatin with 5-FU or capecitabine chemotherapy)
• Previous studies showed that adding trastuzumab to a chemotherapy regimen can improve survival in patients with HER2-positive metastatic stomach cancer.
• Administration: given via intravenous route once every 2 or 3 weeks
• Side effects include:
  • Small risk of heart problems
    • Usually mild with prevalence 2% to 5%
    • Increased risk in patients who have other risk factors for heart disease or concurrently on chemotherapy drugs (e.g. Adriamycin) that increase the risk of heart problems. 
    • These heart problems may go away and can be treated with medication.
  • Infusion reaction
    • Usually mild and subside with pre-medication before infusion

Trastuzumab deruxtecan

• Suitable for patients with HER2-positive advanced or metastatic stomach cancer (around 10-15%) 
• Trastuzumab deruxtecan is considered as second-line or subsequent therapy for stomach cancer patients whose disease progressed after previous anticancer treatment(s).
• Administration: given via intravenous route once every 3 weeks
• Side effects:
  • Low blood cell counts, which can increase the risk of infections and bleeding
  • Nausea and vomiting
  • Diarrhoea or constipation 
  • Loss of appetite
  • Fever
  • Feeling tired
  • Hair loss
  • Rare but serious and life threatening: lung disease (coughing, wheezing, trouble breathing, or fever), heart damage 

Ramucirumab

• A targeted agent that inhibits angiogenesis (formation of new blood vessels) in the tumour, which cuts off nutritional supply to the tumour and stops the cancer from growing.
• Administration: infusion through veins (intravenous infusion), every 2 weeks
• Usually give together with chemotherapy drug(s) (e.g. paclitaxel)
• Suitable for patients who failed first-line chemotherapy
• Side effects:
  • Diarrhoea (around 14%)
  • Low sodium level 
  • Headache
  • High blood pressure
  • Less common but possibly serious: blood clots, severe bleeding, holes forming in the stomach or intestines, problems with wound healing

Zolbetuximab

• Zolbetuximab is a targeted agent that targets Claudin 18.2. It is used in patients with advanced gastric cancer that is HER2-negative and has high amounts of Claudin 18.2 on their cell surface.
• It is used together with combination chemotherapy with FOLFOX or Xelox.
• Administration: infusion through veins (intravenous infusion), every 2-3 weeks
• Side effects:
  • Nausea/ vomiting
  • Diarrhea
  • Fatigue
  • Decreased appetite
  • Stomach pain
  • Weight loss
  • Numbness at fingertips and toes
  • Less common but possibly serious: risk of infection, bleeding, deranged liver function, electrolyte disturbance such as sodium, potassium and magnesium

Other targeted therapies for stomach cancer

• A small number of stomach cancer patients express mutations in the following genes, which could be targeted by the corresponding drugs below:

• These targeted therapies are considered as second-line or subsequent therapy for stomach cancer patients whose disease progressed after previous anti-cancer treatment(s). 

Immunotherapy

• Immunotherapy has emerged as an important treatment option in metastatic stomach cancer.
• Examples: Pembrolizumab, nivolumab ± ipilimumab, dostarlimab
• Pembrolizumab or nivolumab can be combined with chemotherapy as firstline treatment in advanced stomach cancer with positive or high expression of the PD-L1 protein
• Pembrolizumab, nivolumab and ipilimumab, or dostarlimab can be considered for MSI-H or dMMR stomach cancer in any line of treatment
• Administration: given every 2-6 weeks, intravenous infusion
• Common side effects include skin reactions, flu-like symptoms, diarrhoea, weight changes, endocrine dysfunction

Diet changes, among others, are necessary to reduce overall risks of stomach cancer. These include:

• Increasing consumption of fresh fruits and vegetables
  • Vegetables like broccoli, Chinese cabbage, cauliflower and kale contain substances which help break down carcinogens (substances that cause cancer) in the body
  • Vegetables and fruits rich in beta-carotene like carrots, mangoes and papaya, help enhance immunity, which can directly reduce risks of stomach cancer
  • Fruits containing high levels of vitamin C such as citrus fruits and strawberries contain antioxidants which can break down free radicals. Chronic cell damage by these free radicals may cause stomach cancer.
• Avoid high sodium diet:
  • Pickled and smoked food contain carcinogenic compounds formed during production.
    • Sausages
    • Salted egg
    • Ham and bacon
    • Salted fish
  • Avoid deep-fried food as its processing may produce carcinogens and free radicals that can damage the stomach mucosal cells. 
    • Free radicals reduce the oxygen content of tissues in the body, causing damage over time.
• Prevent H. pylori infections
  • Frequent hand washing
  • Avoiding contact with excrement or vomitus
• Regular checkups
  • People falling under these categories are recommended to have an upper endoscopy (of the stomach) once yearly:
    • Over 40 years of age
    • A family history of stomach cancer

American Cancer Society. Stomach cancer. (accessed January 2025). 

Cancer Council. Stomach Cancer.  (accessed January 2025).  

Hong Kong Cancer Registry. Overview of Hong Kong Cancer Statistics of 2022. Hong Kong Hospital Authority; Oct 2024. (accessed January 2025). 

Macmillan Cancer Support. Stomach Cancer (accessed January 2025).  

NCCN Guidelines Gastric Cancer Version 5.2024.  

NCCN Guidelines for Patients. Stomach Cancer, 2023.  

Smart Patient (by Hospital Authority): Stomach cancer 

Special thanks to Mr. Joshua Tang, Mr. Matthew Ho-Fan Cheng (Class M23), medical student of Li Ka Shing Faculty of Medicine, the University of Hong Kong, and Dr. Wendy Wing-Lok Chan, Department of Clinical Oncology, the University of Hong Kong for authoring and editing this article.

Last updated on 14th Jan 2025.