Introduction to GI cancer
This page provides an overview of gastrointestinal (GI) cancers, the associated disease burden and clinical considerations relating to the most common GI tumor types.
GI tract cancer is a collective term used to describe cancers that affect the digestive system. Worldwide, the most commonly diagnosed GI cancers include: colorectal cancer (CRC), gastric cancer, liver cancers (e.g. hepatocellular carcinoma [HCC]), esophageal cancer and pancreatic cancer.1
Less common GI cancers include those affecting the anus, appendix, bile duct, gallbladder and small intestine,2,3 as well as GI neuroendocrine tumors (NETs) and stromal tumors (GISTs), which are characterized by their cell type of origin.4,5
Watch Dr Victoria Zazulina (Corporate VP and Global Head of Oncology Medicine) discuss Boehringer Ingelheim’s research focus on GI cancers in the video below.
Dr Victoria Zazulina explains why treating GI cancers represents an area of focus for Boehringer Ingelheim. Video filmed in 2019.
GI cancers are responsible for more cancer-related deaths than any other type of cancer.6 In 2020, they accounted for an estimated 3.5 million deaths worldwide, with a further 5.0 million new cases diagnosed in the same year.6
Common GI cancers: global incidence and mortality6
*Global data, both sexes, all ages; **CRC, gastric cancer, esophageal cancer, pancreatic cancer and liver cancer.
CRC, colorectal cancer; GI, gastrointestinal.
Common types of GI cancer
CRC is the most common type of GI cancer, with 1.9 million new cases diagnosed worldwide in 2020, making it the third most common of all organ cancers, after lung and breast.6
In the same year, gastric (or stomach), liver, esophageal and pancreatic cancers were ranked the fifth, sixth, eighth and twelfth most commonly diagnosed cancers, with 1.1, 0.9, 0.6 and 0.5 million new cases worldwide, respectively.6
Incidence of common GI cancers in 20206
CRC, colorectal cancer; GI, gastrointestinal.
Common GI cancers ‘at a glance’
CRC occurs when a growth in the lining of the large intestine (colon), or at its end (rectum), becomes cancerous. It is one of the leading causes of cancer-related deaths in men and women, worldwide.6
Approximately 25% of patients with CRC present with metastases at the time of initial diagnosis, and almost a half go on to develop metastases at some point, contributing to its high mortality rate.7
Location of the colon and rectum within the digestive system
Common symptoms include: changes in bowel habits, general or localized abdominal pain, weight loss without other specific causes, weakness, iron deficiency and anemia.8
Risk factors include: age, inflammatory bowel disease, family history, elevated body mass index, reduced physical activity, alcohol consumption and cigarette smoking, as well as a number of dietary factors. High consumption of processed and red meat is thought to contribute to increased risk, while high fruit and vegetable intake is thought to confer protection9
Staging: staging of metastatic CRC should include clinical examination, blood counts, liver and renal function tests, carcinoembryonic antigen evaluation, and a computed tomography (CT) or magnetic resonance imaging (MRI) scan of the abdomen and chest.7 Additionally, a colonoscopy is often performed as part of initial diagnostic procedures.8 The optimum therapeutic strategy is further determined by an evaluation of the patient’s general condition, organ function and presence of any relevant comorbid (non-malignant) diseases.7
Management (first-line standard of care):
The prevalence of gastric (or stomach) cancer varies significantly around the world.6,13 The highest rates are seen in Eastern Asia, Eastern Europe and South America, and the lowest in North America and Western Europe.13 Over the last 60 years, there has been a gradual decline in new cases across North America and Western Europe and, more recently, in higher-prevalence regions.13
Location of the stomach within the digestive system
Common symptoms include: weight loss, dysphagia, dyspepsia, vomiting, early satiety and/or iron deficiency anemia.13
Risk factors include:13
Management (first-line standard of care):13
Liver cancer is the third most common form of GI cancer.6 There are two major subtypes: HCC and intrahepatic bile duct cancer. HCC is the more common of the two, with rates increasing globally for the last 20 years (and predicted to continue to increase until 2030).14
Location of the liver within the digestive system
Common symptoms include: pain, fatigue, weight loss and obstructive syndromes, such as ascites and jaundice15
Risk factors include: chronic liver disease, liver cirrhosis and hepatitis infection.14
Staging and management: several staging systems have been developed, including the Barcelona Clinic Liver Cancer (BCLC) system. BCLC staging links tumor stage, liver function, cancer-related symptoms and performance status (PS) to an evidence-based treatment algorithm:14
There are two main subtypes of esophageal cancer – squamous cell carcinoma (SCC) and adenocarcinoma. SCC occurs more frequently in the upper and middle parts of the esophageal tract, while adenocarcinoma usually occurs in the lower part of the esophagus, near the junction with the stomach.16
Although SCC accounts for approximately 90% of cases of esophageal cancer, adenocarcinoma is associated with a higher mortality rate. Indeed, adenocarcinoma mortality rates have now surpassed those of SCC in some countries.16,17
Location of the esophagus within the digestive system
Common symptoms include: difficult or painful swallowing, progressive weight loss, nausea, vomiting, loss of appetite, chest pain and hoarseness16
Risk factors include:17
Staging should include:17
Management (first-line standard of care):17
Uncommon tumors at a glance
Anal cancer represents only 1.5% of GI cancers, but there has been an increase in the global incidence in recent decades.18 SCC of the anus is strongly associated with human papillomavirus (HPV) infection, which represents the causative agent in 80–85% of cases.19
Location of the anus within the digestive system
Common symptoms include: a perianal mass, non-healing ulcers, pain, bleeding, itching, discharge, fecal incontinence and fistulae.19
Risk factors include: HPV infection, anal intercourse, a high lifetime number of sexual partners, human immunodeficiency virus infection, immune suppression in transplant recipients, use of immunosuppressants, a history of other HPV-related cancers, autoimmune disorders, social deprivation and cigarette smoking.19
Staging should include: MRI of the pelvis or, if not available, endo-anal ultrasound. MRI has good spatial resolution and contrast, providing information on tumor size, local extent and spread. Distant metastases can be assessed with CT of the thorax and abdomen. 18F-FDG-PET/CT has a high sensitivity for identifying involved lymph nodes. Needle aspiration biopsy is usually only carried out for clinically palpable inguinal nodes or those enlarged >10 mm on CT or MRI. Sentinel lymph node biopsy can reveal micrometastatic spread of the disease.19
Neuroendocrine neoplasms (NENs) are relatively rare, comprising ~2% of all malignancies; however, 62–67% of NENs occur in the GI tract.20
GI NETs arise from the diffuse neuroendocrine system and comprise a heterogeneous group of tumors that can present with a variety of clinical symptoms.21,22 The risk factors are not well characterized, but multiple endocrine neoplasia type 1 syndrome is implicated, and genetic and familial associations have been observed.20
NENs are broadly divided into two groups on the basis of clinical behavior, histology and proliferation rate:20,22
Therapeutic decision-making is based on tumor grade, somatostatin receptor expression, proliferative activity and tumor growth; 12–22% of patients present with metastatic disease.20-22 Potential treatment options include surgery, somatostatin analogues, chemotherapy, sunitinib, peptide receptor radionuclide therapy and interferon alpha.22
GISTs account for approximately 1% of all GI tumors, but they are the most common mesenchymal tumors of the GI tract.5 They are thought to grow from specialized interstitial cells of Cajal that function as pacemaker-like intermediates between the GI autonomic nervous system and smooth muscle cells, regulating GI motility and autonomic nerve function.5,23
GISTs may be either malignant or benign and can occur anywhere in or near the GI tract; they appear most often in the stomach (60%) or small intestine (30%). They are typically diagnosed in adults aged 40–70 years.5,23
Some people with GISTs may experience pain or swelling in the abdomen, nausea, vomiting, loss of appetite or weight loss. Anemia, black and tarry stools and vomiting of blood can also occur in cases where GISTs cause GI bleeding.23 A family history of GISTs is generally associated with more symptomatic disease and multiple (rather than single, ‘sporadic’) tumors.23
The formation of GISTs is most commonly associated with mutations in the tyrosine-protein kinase KIT gene (approximately 80% of cases) and the platelet-derived growth factor receptor alpha gene (PDGFRA; approximately 10% of cases).23
Treatment may involve surgery and/or use of tyrosine kinase inhibitors (TKIs), depending on the extent of disease and TKI sensitivity.5
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Pourhoseingholi MA, et al. Gastro Hepat Bed to Bench 2015;8(1):19.
GI Cancer Alliance. GI Cancers. http://www.gicancersalliance.org/gi-cancers (Accessed: January 2021).
Hirabayashi K, et al. Front Oncol 2013;3:2.
National Cancer Institute. Gastrointestinal Stromal Tumors Treatment (PDQ®)–Health Professional Version. https://www.cancer.gov/types/soft-tissue-sarcoma/hp/gist-treatment-pdq (Accessed: January 2021).
International Agency for Research on Cancer (IARC). Estimated number of new cases and deaths of cancer in 2020. https://gco.iarc.fr/today/home (Accessed: January 2021).
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U.S. National Library of Medicine. Genetics Home Reference: Gastrointestinal stromal tumor. https://ghr.nlm.nih.gov/condition/gastrointestinal-stromal-tumor#resources (Accessed: January 2021).
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Page last updated: January 2021
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