Gastric cancer is the fifth most common cancer in the world and the third leading cause of cancer death in both sexes worldwide (723,000 deaths, 9.8% of the total). The highest estimated mortality rates are in Eastern Asia (24 per 100,000 in men, 9.8 per 100,000 in women), and the lowest are in Northern America (2.8 and 1.5, respectively). High mortality rates are also present in both sexes in Central and Eastern Europe and in Central and South America. It is a difficult disease to cure in Western countries, mainly because most patients present with advanced disease. 50% involve the pylorus, 25% the lesser curve and 10% the cardia. 2-8% of gastric cancers are lymphomas.
- The most recent statistics quoted on the Cancer Research UK website are for 2008. This shows that 4,923 new diagnoses of gastric cancer were made in the UK in 2008.
- There are unexplained wide international variations, being especially common in Japan, China and parts of South America.
- There has been a marked increase in the incidence of adenocarcinoma of the proximal stomach (especially around the cardia) over a period of two decades, with a corresponding decrease in incidence in distal gastric cancer.
- Increasing age: 95% of gastric cancers occur in those aged over 55 years and this rises steeply from the age of 60.
- It is more common in men than in women. In the UK, the ratio is 1.8:1.
- It is strongly associated with poor socio-economic status.
- Helicobacter pylori: this can double the risk of gastric cancer in infected individuals. A certain type of H. pylori (cagA-positive) can increase the risk even more. The relationship between infection and cancer in the cardia region, however, is currently unclear and it is possible that eradication of H. pylori may increase the risk of cardia cancer.
- Diet: diets where levels of fresh fruit and vegetable consumption are low increase the risk of gastric cancer. A high level of salt and preserved foods may also increase the risk.
- Atrophic gastritis, pernicious anaemia, post-gastrectomy, Ménétrier's disease.
- Familial risk: families with a very high incidence have been identified. There is a 2- to 3-fold increased risk to first-degree relatives of gastric cancer patients. There is a link between E-cadherin gene mutations and some familial gastric cancers.
- Blood group A (relative risk is 1.2).
- Nonspecific with dyspepsia, weight loss, vomiting, dysphagia and anaemia.
- Early gastric cancer often has symptoms suggesting a benign aetiology. 70% of patients with early gastric cancer only have symptoms of uncomplicated dyspepsia and are not complicated by anaemia, dysphagia, or weight loss.
- Clinical diagnosis is therefore very inaccurate in distinguishing between organic and non-organic disease. All at-risk patients with dyspepsia should be considered for endoscopy.
- The majority of patients present with advanced disease and alarm symptoms such as weight loss, vomiting, anorexia, abdominal pain and anaemia.
- Treatment with antisecretory drugs may delay diagnosis or result in a misdiagnosis on first endoscopy. Proton pump inhibitors may appear to heal malignant ulcers. One study found, however, that such delay does not affect survival or long-term outcome.
- Signs suggesting incurable disease - eg, epigastric mass, hepatomegaly, jaundice, ascites, Troisier's sign (an enlarged left supraclavicular node - Virchow's node), acanthosis nigricans.
- Significant acute gastrointestinal bleeding.
Urgent referral (within two weeks)
- Patients of any age with dyspepsia who present with any of the following should have an urgent referral for endoscopy or referral to a specialist in upper gastrointestinal cancer:
- Chronic gastrointestinal bleeding.
- Progressive dysphagia.
- Progressive unintentional weight loss.
- Persistent vomiting.
- Iron-deficiency anaemia.
- Epigastric mass.
- Suspicious barium meal result.
- Patients aged 55 years and older with unexplained and persistent recent-onset dyspepsia.
- Patients presenting with the following, even in the absence of dyspepsia, should have an urgent referral for endoscopy or referral to a specialist in upper gastrointestinal cancer:
- Unexplained upper abdominal pain and weight loss, with or without back pain.
- Upper abdominal mass.
- Obstructive jaundice (depending on clinical state).
- Consider urgent referral for:
- Persistent vomiting and weight loss in the absence of dyspepsia.
- Unexplained weight loss.
- Iron-deficiency anaemia.
- Consider urgent referral for patients with unexplained worsening of their dyspepsia who are known to have any of the following risk factors:
- Barrett's oesophagus.
- Atrophic gastritis (pernicious anaemia).
- Intestinal metaplasia.
- Peptic ulcer surgery more than 20 years previously.
- H. pylori status should not affect the decision to refer for suspected cancer.
- Check FBC (possible anaemia) and LFTs.
- Rapid-access flexible endoscopy is the investigation of choice. Biopsies can be taken and small lesions evaluated more fully than is possible with radiological studies. Antisecretory therapy should be ideally withheld until after endoscopy, to avoid misdiagnosis.
- Enhancements such as chromoendoscopy (use of dyes to highlight various aspects of the gastric mucosa), narrow band imaging and autofluorescence are currently being investigated.
- All gastric ulcers should be biopsied (multiple ulcer edge biopsies), as even malignant ulcers may appear to heal on drug treatment. Gastric ulcers should also be followed up, until healing, with repeat biopsy.
Patients with gastric cancer should undergo careful pre-operative staging to enable appropriate management.
- Spread is local, lymphatic, blood-borne and transcoelomic - eg to ovaries (Krukenberg's tumour).
- Initial staging assessment should include spiral CT scanning of the thorax and abdomen to determine the presence or absence of metastatic disease.
- In the absence of metastatic disease, assessment of operability is preferably made by endoscopic ultrasound.
- Adjuncts to staging include chest radiography, transabdominal ultrasound, magnetic resonance imaging, bronchoscopy and laparoscopy.
Tumour, node, metastasis (TNM) stagingTX, NX or MX indicates 'not assessed'.
T0 - no evidence of primary tumour.
Tis - carcinoma in situ (intraepithelial).
T1 - invades lamina propria or submucosa.
T2 - invades muscularis propria or subserosa (not visceral peritoneum).
T3 - penetrates visceral peritoneum but not adjacent structures.
T4 - invades adjacent structures (spleen, colon, etc).
N0 - no LN metastasis.
N1 - 1-6 lymph nodes.
N2 - 7-15 lymph nodes.
N3 - more than 15 lymph nodes.
M0 - no distant metastasis.
M1 - distant metastasis, in portal lymph node, mesenteric, retroperitoneal or more distant.
- All patients with gastric cancer should be screened for nutritional deficiency and consideration of nutritional support.
- Symptom control includes treatment for pain, nausea, constipation, depression and mouth care.
- Surgery is the treatment of choice for gastric cancer. The most important indicator for resectability and survival after surgery is early diagnosis and therefore early stage of disease at operation. Operative mortality varies across Europe for reasons that are unclear. One study found an overall rate of 8.9%.
- Distal (antral) tumours should be treated by subtotal gastrectomy and proximal tumours by total gastrectomy.
- Limited gastric resections should presently only be used for palliation or in the very elderly.
- Patients with curable cancers of the stomach should normally undergo a D2 lymphadenectomy (removing distant lymph nodes) although Japanese studies suggest that in some cancers, adequate local clearance may be sufficient and can be curative, even in the presence of lymph node metastases.
- The distal pancreas and spleen should not be removed as part of a resection for a cancer in the distal two thirds of the stomach. There is increasing evidence that removal of the spleen has an adverse effect on prognosis. The distal pancreas should be removed only when there is direct invasion and still a chance of a curative procedure in patients with carcinoma of the proximal stomach. Resection of the spleen and splenic hilar nodes should only be considered in patients with tumours of the proximal stomach located on the greater curvature/posterior wall of the stomach close to the splenic hilum where the incidence of splenic hilar nodal involvement is likely to be high.
Chemotherapy and radiotherapy
- Perioperative combination chemotherapy has become the standard of care for localised gastric cancer throughout the UK and most of Europe.
- Adjuvant chemotherapy without radiotherapy after surgery is not currently standard procedure in the UK but may be helpful in high-risk patients, especially those who have not had neoadjuvant chemotherapy.
- Postoperative chemoradiotherapy is also not current standard UK practice but may be of benefit in high-risk patients.
- Intraperitoneal chemotherapy remains investigational.
- 5-FU is the most effective chemotherapeutic agent. A combination of 5-fluorouracil (5-FU) with other agents is superior to single agent treatment. Various combinations are being explored, of which epirubicin and cisplatin are the most commonly used in the UK.
- A multidisciplinary approach to care is essential.
- Palliative care is often needed for obstruction, pain or haemorrhage and involves judicious use of drugs, surgery and radiotherapy.
- Palliative chemotherapy for locally advanced and/or metastatic disease provides quality of life and survival benefit. Various combinations are being explored, including epirubicin, cisplatin and continuous infusion of 5-FU (ECF) and epirubicin with oxaliplatin and capecitabine. Capecitabine is now endorsed by the National Institute for Health and Care Excellence (NICE) in combination with a 'platin' drug for the palliative treatment of advanced gastric cancer. Pre-operative downstaging of locally advanced disease with chemotherapy may enable resection of previously inoperable cancers.
- Currently there is no indication to recommend second-line chemotherapy. Its role should remain in the context of a clinical trial. Second-line palliative chemotherapy following failure of first-line chemotherapy is still investigational but a combination of folinic acid, 5-FU and oxaliplatin, or docetaxel with or without epirubicin, have demonstrated significant benefits.
- Trastuzumab, in combination with cisplatin and capecitabine or 5-FU, has been endorsed by NICE for use in patients with a certain type of metastatic adenocarcinoma of the stomach or gastro-oesophageal junction (that which has high levels of the antigen HER2) who have not received prior treatment for their metastatic disease.
- Those with distal obstructing tumours may benefit from a subtotal gastrectomy or gastrojejunostomy. Stenting of gastric cardia tumours relieves dysphagia.
- Endoscopic laser therapy may be of help in unresectable obstruction or to control bleeding lesions.
- Blood transfusion may be appropriate for symptomatic anaemia.
- Corticosteroids or megestrol acetate should be considered for management of anorexia.
- Coeliac plexus nerve blocks may be effective in controlling resistant pain.
- Palliative techniques currently in the research stage include photodynamic therapy, argon plasma therapy, ethanol injections and irradiation and stenting combined.
In the UK:
- Overall survival rate is 15%.
- 11% of people live for at least ten years.
- Younger people tend to survive longer. The five-year survival rate for people under 50 is 16-22% compared to 5-12% for people over 70.
American studies suggest that Asian people have a better prognosis.
- A diet with high intakes of fruit and vegetables (at least five servings per day), smoking cessation and reduction of excessive alcohol intake are likely, although not yet proven, to reduce the incidence of gastric cancer. Vitamin supplements are not known to have any effect.
- Control of obesity is likely to be an important factor.
- The usefulness of surveillance endoscopy in Barrett's oesophagus and in the investigation of dyspepsia remains to be confirmed.
- H. pylori eradication is likely to be important but its effect on gastro-oesophageal cancer remains to be determined
- COX-2 may be a biomarker for gastric carcinoma and its measurement in gastric biopsies may be a useful secondary preventative strategy. Ironically, aspirin, non-steroidal anti-inflammatory drugs and other COX-2 inhibitors may be beneficial in preventing gastric carcinoma but further research is needed.
Further reading and references
Gastric cancer: ESMO–ESSO–ESTRO Clinical Practice Guidelines for diagnosis treatment and follow-up; European Society for Medical Oncology and others (2013)
Thrumurthy SG, Chaudry MA, Hochhauser D, et al; The diagnosis and management of gastric cancer. BMJ. 2013 Nov 4347:f6367. doi: 10.1136/bmj.f6367.
Stomach Cancer Estimated Incidence, Mortality and Prevalence Worldwide in 2012; International Agency for Research on Cancer, World Health Organization
Stomach cancer incidence statistics; Cancer Research UK
Brenner H, Rothenbacher D, Arndt V; Epidemiology of stomach cancer. Methods Mol Biol. 2009472:467-77. doi: 10.1007/978-1-60327-492-0_23.
Guidelines for the management of oesophageal and gastric cancer; British Society of Gastroenterology (June 2011)
Axon A; Symptoms and diagnosis of gastric cancer at early curable stage. Best Pract Res Clin Gastroenterol. 200620(4):697-708.
Panter SJ, O'Flanagan H, Bramble MG, et al; Empirical use of antisecretory drug therapy delays diagnosis of upper Aliment Pharmacol Ther. 2004 May 119(9):981-8.
Referral for suspected cancer; NICE Clinical Guideline (2005)
Mackay S, Hayes T, Yeo A; Management of gastric cancer. Aust Fam Physician. 2006 Apr35(4):208-11.
Lepage C, Sant M, Verdecchia A, et al; Operative mortality after gastric cancer resection and long-term survival Br J Surg. 2010 Feb97(2):235-9.
Gastric cancer (advanced) - capecitabine; NICE Technology Appraisal Guideline, July 2010
Trastuzumab for the treatment of HER2-positive metastatic gastric cancer; NICE Technology Appraisal Guideline, November 2010
Anorexia and Cachexia; International Network for Cancer Treatment and Research, 2009
Kambadakone A, Thabet A, Gervais DA, et al; CT-guided celiac plexus neurolysis: a review of anatomy, indications, technique, Radiographics. 2011 Oct31(6):1599-621.
Statistics and outlook for stomach cancer; Cancer Research UK
Fock KM; Review article: the epidemiology and prevention of gastric cancer. Aliment Pharmacol Ther. 2014 Aug40(3):250-60. doi: 10.1111/apt.12814. Epub 2014 Jun 10.
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