Stomach Cancer

Stomach cancer was the sixth commonest cancer in Hong Kong in 2021. It accounted for 3.4% of all new cancer cases. There were 1,306 new cases of stomach cancer in 2021, including 762 males and 544 females. The male-female ratio of stomach cancer incidence was 1.4:1. The crude incidence rate was 16 per 100,000 standard population. Most of the stomach cancer patients were diagnosed at an older age. 883 of these new patients were over the age of 65 in 2021.

Stomach cancer was the sixth leading cause of cancer deaths in Hong Kong. In 2021, it claimed 631 deaths, accounting for 4.2% 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 stomach in a semi-solid 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 inclue 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 an antibiotics can effectively kill the disease. 
  • Testing for H. pylori is recommended if one has had a first-degree relative, such as parents, 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 most 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 most at risk:
    • 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 (OGD): 
  • An upper gastrointestinal 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 be tested in the lab (biopsy)
    
• 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 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
• HER2 (ERBB2) status
• 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

• Endoscopic mucosal resection (EMR) 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). EMR is done using an endoscope placed through the mouth, throat and into the stomach. Salt water 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 through an incision in the abdomen. 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, usually 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.

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 after stomach surgery:

• Capectabine and oxaliplatin (Xelox)
  • A regimen of two drugs: oral capecitabine (xeloda) and intravenous oxaliplatin. This regimen is usually given every 3 weeks for a total of 8 cycles.
• TS-ONE/ S-1
  • This is an oral medication that combines three pharmacological compounds:
    • Tegafur becomes 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.
• 5FU, leucovorin, oxaliplatin and docetaxel (taxotere) (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. capecitabine) 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, PDL1, MMR/MSI), 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
• PD-L1
• MMR/ MSI
• 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 and platinum doublet is typically the preferred backbone regimen for most patients.
• Commonly used chemotherapy for metastatic stomach cancer include:
  • Oxaliplatin/ Cisplatin/ Carboplatin
  • 5FU: infusional 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
• Trastuzumab is added to first-line platinum-based chemotherapy (e.g. oxaliplatin, cisplatin or carboplatin with 5FU chemotherapy)
• Previous studies showed that adding trastuzumab to a chemotherapy regimen can improve survival in patients with HER2-positive metastatic stomach cancer.
• Administration: given every 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.
  • Infusional reaction
    • Usually mild and subside with pre-medication before infusion

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

Immunotherapy

• Immunotherapy has emerged as an important treatment option in metastatic stomach cancer.
• Pembrolizumab/ nivolumab
  • Pembrolizumab/ nivolumab can be combined with chemotherapy as first-line treatment in advanced stomach cancer
  • Pembrolizumab/ nivolumab can be used as third-line treatment for stomach cancer
  • Administration: given every 2-3 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
  • Cabbages 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 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

Hong Kong Cancer Registry, 2020, Stomach cancer

The Hong Kong Anti-Cancer Society: Stomach cancer (Chinese only)

Smart Patient (by Hospital Authority): Stomach cancer

American Society of Clinical Oncology (ASCO): Stomach cancer

Canadian Cancer Society: 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 18th Dec, 2023.