Stomach cancer accounts for an estimated 26,240 cases and about 10,800 deaths in the US annually (1). Gastric adenocarcinoma accounts for 95% of malignant tumors of the stomach; less common are localized gastric lymphomas and leiomyosarcomas. Stomach cancer is the 2nd most common cancer worldwide, but the incidence varies widely; incidence is extremely high in Japan, China, Chile, and Iceland. In the US, incidence has declined in recent decades to the 7th most common cause of death from cancer. In the US, it is most common among blacks, Hispanics, and American Indians. Its incidence increases with age; > 75% of patients are > 50 years.
Helicobacter pylori infection is a risk factor for some stomach cancers.
Autoimmune atrophic gastritis and various genetic factors are also risk factors. Dietary factors are not proven causes; however, the WHO International Agency for Research on Cancer (IARC) has reported a positive association between consumption of processed meat and stomach cancer (1). Smoking is a risk factor for stomach cancer, and people who smoke may have an impaired response to treatment.
Gastric polyps can be precursors of cancer. Inflammatory polyps may develop in patients taking NSAIDs, and fundic foveolar polyps are common among patients taking proton pump inhibitors. Adenomatous polyps, particularly multiple ones, although rare, are the most likely to develop cancer. Cancer is particularly likely if an adenomatous polyp is > 2 cm in diameter or has a villous histology. Because malignant transformation cannot be detected by inspection, all polyps seen at endoscopy should be removed.
Gastric adenocarcinomas can be classified by gross appearance:
Protruding: The tumor is polypoid or fungating.
Penetrating: The tumor is ulcerated.
Superficial spreading: The tumor spreads along the mucosa or infiltrates superficially within the wall of the stomach.
Linitis plastica: The tumor infiltrates the stomach wall with an associated fibrous reaction that causes a rigid “leather bottle” stomach.
Miscellaneous: The tumor shows characteristics of ≥ 2 of the other types; this classification is the largest.
Prognosis is better with protruding tumors than with spreading tumors because protruding tumors become symptomatic earlier.
Initial symptoms of stomach cancer are nonspecific, often consisting of dyspepsia suggestive of peptic ulcer. Patients and physicians alike tend to dismiss symptoms or treat the patient for acid disease. Later, early satiety (fullness after ingesting a small amount of food) may occur if the cancer obstructs the pyloric region or if the stomach becomes nondistensible secondary to linitis plastica. Dysphagia may result if cancer in the cardiac region of the stomach obstructs the esophageal outlet. Loss of weight or strength, usually resulting from dietary restriction, is common. Massive hematemesis or melena is uncommon, but secondary anemia may follow occult blood loss. Occasionally, the first symptoms are caused by metastasis (eg, jaundice, ascites, fractures).
Physical findings may be unremarkable or limited to heme-positive stools. Late in the course, abnormalities include an epigastric mass; umbilical, left supraclavicular, or left axillary lymph nodes; hepatomegaly; and an ovarian or rectal mass. Pulmonary, CNS, and bone lesions may occur.
Differential diagnosis of stomach cancer commonly includes peptic ulcer and its complications.
Patients suspected of having stomach cancer should have endoscopy with multiple biopsies and brush cytology. Occasionally, a biopsy limited to the mucosa misses tumor tissue in the submucosa. X-rays, particularly double-contrast barium studies, may show lesions but rarely obviate the need for subsequent endoscopy.
Patients in whom cancer is identified require CT of the chest and abdomen to determine extent of tumor spread. If CT is negative for metastasis, endoscopic ultrasonography should be done to determine the depth of the tumor and regional lymph node involvement. Findings guide therapy and help determine prognosis.
Basic blood tests, including CBC, electrolytes, and liver function tests, should be done to assess anemia, hydration, general condition, and possible liver metastases. The carcinoembryonic antigen (CEA) level should be measured before and after surgery.
Screening with endoscopy is used in high-risk populations (eg, Japanese) but is not recommended in the US. Follow-up screening for recurrence in treated patients consists of endoscopy and CT of the chest, abdomen, and pelvis. If an elevated CEA level dropped after surgery, follow-up should include CEA levels; a rise signifies recurrence.
Prognosis depends greatly on stage but overall is poor (5-year survival: < 5 to 15%) because most patients present with advanced disease. If the tumor is limited to the mucosa or submucosa, 5-year survival may be as high as 80%. For tumors involving local lymph nodes, survival is 20 to 40%. More widespread disease is almost always fatal within 1 year. Gastric lymphomas have a better prognosis (see Uncommon Gastritis Syndromes : Mucosa-associated lymphoid tissue (MALT) lymphoma and see Non-Hodgkin Lymphomas).
Stomach cancer treatment decisions depend on tumor staging and the patient’s wishes (some may choose to forgo aggressive treatment—see Advance Directives).
Curative surgery involves removal of most or all of the stomach and adjacent lymph nodes and is reasonable in patients with disease limited to the stomach and perhaps the regional lymph nodes (< 50% of patients). Adjuvant chemotherapy or combined chemotherapy and radiation therapy after surgery may be beneficial if the tumor is resectable.
Resection of locally advanced regional disease results in a 10-month median survival (vs 3 to 4 months without resection).
Metastasis or extensive nodal involvement precludes curative surgery, and, at most, palliative procedures should be undertaken. However, the true extent of tumor spread often is not recognized until curative surgery is attempted. Palliative surgery typically consists of a gastroenterostomy to bypass a pyloric obstruction and should be done only if the patient’s quality of life can be improved. In patients not undergoing surgery, combination chemotherapy regimens (5-fluorouracil, doxorubicin, mitomycin, cisplatin, or leucovorin in various combinations) may produce temporary response but little improvement in 5-year survival. In recent years, targeted therapies using trastuzumab for tumors that overexpress human epidermal growth factor receptor 2 (HER2+ tumors) and ramucirumab (a vascular endothelial growth factor [VEGF] inhibitor) in conjunction with chemotherapy have been used in advanced cancer. Immunotherapy such as with pembrolizumab is approved for use in patients with programmed cell death ligand 1 (PD-L1)–positive advanced or metastatic gastric cancer. (See also the National Comprehensive Cancer Network's guidelines on gastric cancer.) Radiation therapy is of limited benefit.
Helicobacter pylori infection is a risk factor for some stomach cancers.
Initial symptoms are nonspecific and often resemble those of peptic ulcer disease.
Screening with endoscopy is used in high-risk populations (eg, Japanese) but is not recommended in the US.
Overall, survival is poor (5-year survival: 5 to 15%) because many patients present with advanced disease.
Curative surgery, perhaps with combined chemotherapy and radiation therapy, is reasonable in patients with disease limited to the stomach and perhaps the regional lymph nodes.