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Home > Health Library > Gastric Cancer Treatment (PDQ®): Treatment - Health Professional Information [NCI]
This information is produced and provided by the National Cancer Institute (NCI). The information in this topic may have changed since it was written. For the most current information, contact the National Cancer Institute via the Internet web site at http://cancer.gov or call 1-800-4-CANCER.
Incidence and Mortality
Estimated new cases and deaths from gastric cancer in the United States in 2020:
Management of adenocarcinoma histology, which accounts for 90% to 95% of all gastric malignancies, is discussed in this summary. There are changing epidemiologic patterns in the United States regarding the anatomic location of esophagogastric cancers, with a trend of decreased occurrence of distal or noncardia gastric cancers. However, in persons aged 25 to 39 years, there has been an increase in the incidence of noncardia gastric cancers from 0.27 cases per 100,000 individuals (1977–1981) to 0.45 cases per 100,000 individuals (2002–2006). Additional studies are needed to confirm the observed increases in noncardia gastric cancers in this specific age group.
In contrast to the overall stable trend for noncardia gastric cancers, earlier studies demonstrated an increased incidence of adenocarcinomas of the gastric cardia of 4% to 10% per year from the mid-1970s to the late 1980s. Similarly, the incidence of gastroesophageal junction adenocarcinomas increased sharply, from 1.22 cases per 100,000 individuals (1973–1978) to 2.00 cases per 100,000 individuals (1985–1990). Since that time, the incidence has remained steady at 1.94 cases per 100,000 individuals (2003–2008). More recent data demonstrate that the incidence of gastric cardia cancers has been relatively stable, although an increase has been observed, from 2.4 cases per 100,000 individuals (1977–1981) to 2.9 cases per 100,000 individuals (2001–2006) in the Caucasian population. The reasons for these temporal changes in incidence are unclear.
In the United States, gastric cancer ranks 14th in incidence among the major types of cancer. While the precise etiology is unknown, acknowledged risk factors for gastric cancer include the following:[5,6,7]
Prognosis and Survival
The prognosis of patients with gastric cancer is related to tumor extent and includes both nodal involvement and direct tumor extension beyond the gastric wall.[8,9] Tumor grade may also provide some prognostic information.
In localized distal gastric cancer, more than 50% of patients can be cured. However, early-stage disease accounts for only 10% to 20% of all cases diagnosed in the United States. The remaining patients present with metastatic disease in either regional or distant sites. The overall survival rate in these patients at 5 years ranges from almost no survival for patients with disseminated disease to almost 50% survival for patients with localized distal gastric cancers confined to resectable regional disease. Even with apparent localized disease, the 5-year survival rate of patients with proximal gastric cancer is only 10% to 15%. Although the treatment of patients with disseminated gastric cancer may result in palliation of symptoms and some prolongation of survival, long remissions are uncommon.
Gastrointestinal stromal tumors occur most commonly in the stomach. (Refer to the PDQ summary on Gastrointestinal Stromal Tumors Treatment [Adult] for more information.)
Other PDQ summaries containing information related to gastric cancer include the following:
There are two major types of gastric adenocarcinoma including the following:
Intestinal adenocarcinomas are well differentiated, and the cells tend to arrange themselves in tubular or glandular structures. The terms tubular, papillary, and mucinous are assigned to the various types of intestinal adenocarcinomas. Rarely, adenosquamous cancers can occur.
Diffuse adenocarcinomas are undifferentiated or poorly differentiated, and they lack a gland formation. Clinically, diffuse adenocarcinomas can give rise to infiltration of the gastric wall (i.e., linitis plastica).
Some tumors can have mixed features of intestinal and diffuse types.
AJCC Prognostic Stage Groups and TNM Definitions
The American Joint Committee on Cancer (AJCC) has designated staging by TNM (tumor, node, metastasis) classification to define gastric cancer.
Radical surgery represents the standard form of therapy that has curative intent. However, the incidences of local failure in the tumor bed and regional lymph nodes, and distant failures via hematogenous or peritoneal routes, remain high. As such, comprehensive staging and evaluation with a multidisciplinary team to determine roles of neoadjuvant, perioperative, and adjuvant combination chemotherapy, surgery, and external-beam radiation therapies should be considered.
Investigators in Europe evaluated the role of perioperative chemotherapy without radiation therapy. Initially, in a randomized phase III trial (MRC-ST02 [NCT00002615]), patients with stage II or higher adenocarcinoma of the stomach or of the lower third of the esophagus were assigned to receive three cycles of epirubicin, cisplatin, and continuous infusion 5-fluorouracil (5-FU) (ECF) before and after surgery or to receive surgery alone. Compared with the surgery group, the perioperative chemotherapy group had a significantly higher overall survival (OS) (hazard ratio [HR]death, 0.75; 95% confidence interval [CI], 0.60–0.93; P = .009).[Level of evidence: 1iiA]
In addition, in the randomized phase III AIO-FLOT4 trial (NCT01216644), patients with resectable disease that was stage T2 or higher and/or node positive received either perioperative epirubicin, cisplatin, and 5-FU or capecitabine (ECF/ECX) (three cycles before and after surgery) or perioperative docetaxel, oxaliplatin, and 5-FU/leucovorin (FLOT) (four 2-week cycles before and after surgery). OS was significantly increased from 35 months with ECF/ECX to 50 months with FLOT (HR, 0.77; 95% CI, 0.63–0.94; P = .012).
In a phase III Intergroup trial (SWOG-9008 [NCT01197118]), 559 patients with completely resected stage IB to stage IV (M0) adenocarcinoma of the stomach and gastroesophageal junction were randomly assigned to receive either surgery alone or surgery plus postoperative chemotherapy (5-FU and leucovorin) and concurrent radiation therapy (45 Gy). With a median follow-up of more than 10 years, a significant survival benefit was reported for patients who received adjuvant combined modality therapy.[Level of evidence: 1iiA] Median OS was 35 months for the adjuvant chemoradiation therapy group and 27 months for the surgery-alone arm (P = .0046). Median relapse-free survival was 27 months in the chemoradiation arm compared with 19 months in the surgery-alone arm (P < .001).
Standard Treatment Options for Stage 0 Gastric Cancer
Standard treatment options for stage 0 gastric cancer include the following:
Stage 0 is gastric cancer confined to mucosa. Experience in Japan, where stage 0 is diagnosed frequently, indicates that more than 90% of patients treated by gastrectomy with lymphadenectomy will survive beyond 5 years. An American series has confirmed these results.
Endoscopic mucosal resection (EMR)
EMR has been studied in Japan and throughout Asia in patients with early-stage tumors with good-risk features (Tis or T1a, diameter ≤2 cm, predominantly differentiated type, without ulcerative findings) that have a lower risk of nodal metastasis. Intramucosal tumors have a lower risk of nodal metastasis than submucosal tumors. Careful patient selection by the above criteria, treatment with an experienced endoscopist, and close surveillance should be considered.
Current Clinical Trials
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
Standard Treatment Options for Stage I Gastric Cancer
Standard treatment options for stage I gastric cancer include the following:
Regional lymphadenectomy is recommended with all of the above procedures. Splenectomy is not routinely performed.
Surgical resection including regional lymphadenectomy is the treatment of choice for patients with stage I gastric cancer. If the lesion is not in the cardioesophageal junction and does not diffusely involve the stomach, subtotal gastrectomy is the procedure of choice, because it has been demonstrated to provide equivalent survival when compared with total gastrectomy and is associated with decreased morbidity.[Level of evidence: 1iiA] When the lesion involves the cardia, proximal subtotal gastrectomy or total gastrectomy (including a sufficient length of esophagus) may be performed with curative intent. If the lesion diffusely involves the stomach, total gastrectomy is required. At a minimum, surgical resection includes greater and lesser curvature perigastric regional lymph nodes. Note that in patients with stage I gastric cancer, perigastric lymph nodes may contain cancer.
EMR has been studied in Japan and throughout Asia in patients with early-stage tumors with good risk features (Tis or T1a, diameter ≤2 cm, predominantly differentiated type, without ulcerative findings) that have a lower risk of nodal metastasis. Intramucosal tumors have a lower risk of nodal metastasis than submucosal tumors. Careful patient selection by the above criteria, treatment with an experienced endoscopist, and close surveillance should be considered.
Postoperative chemoradiation therapy
In patients with node-positive (T1 N1) and muscle-invasive (T2 N0) disease, postoperative chemoradiation therapy may be considered.
Evidence (postoperative chemoradiation therapy):
Because the prognosis is relatively favorable for patients with completely resected stage IB disease, the effectiveness of adjuvant chemoradiation therapy for this group is less clear.
Investigators in Europe evaluated the role of perioperative chemotherapy without radiation therapy.
Evidence (perioperative chemotherapy):
Treatment Options Under Clinical Evaluation for Stage I Gastric Cancer
Treatment options under clinical evaluation for stage I gastric cancer include the following:
Standard Treatment Options for Stages II and III Gastric Cancer
Standard treatment options for stage II gastric cancer and stage III gastric cancer include the following:
No randomized trials of adjuvant chemoradiation versus perioperative chemotherapy have been undertaken.
Due to high risk of locoregional and distant recurrence, consideration for perioperative and postoperative therapy should be considered in addition to surgery.
Surgical resection with regional lymphadenectomy is the treatment of choice for patients with stages II and III gastric cancer and all eligible patients undergo surgery. If the lesion is not in the cardioesophageal junction and does not diffusely involve the stomach, subtotal gastrectomy is the procedure of choice. When the lesion involves the cardia, proximal subtotal gastrectomy or total gastrectomy may be performed with curative intent. If the lesion diffusely involves the stomach, total gastrectomy and appropriate lymph node resection may be required. The role of extended lymph node (D2) dissection is uncertain  and in some series is associated with increased morbidity.[5,6] As many as 15% of selected stage III patients can be cured by surgery alone, particularly if lymph node involvement is minimal (<7 lymph nodes).
Investigators in Europe evaluated the role of perioperative chemotherapy without radiation therapy.
Postoperative (adjuvant) chemoradiation therapy
Postoperative chemoradiation therapy may be considered for patients with stages II and III gastric cancer who have not received neoadjuvant therapy.
Evidence (postoperative [adjuvant] chemoradiation therapy):
Postoperative (adjuvant) chemotherapy
Investigators in Europe evaluated the role of postoperative chemotherapy without radiation therapy.
Evidence (postoperative [adjuvant] chemotherapy):
Treatment Options Under Clinical Evaluation for Stages II and III Gastric Cancer
Treatment options under clinical evaluation for stages II and III gastric cancer include the following:
All newly diagnosed patients with stages II and III gastric cancer should be considered candidates for clinical trials.
Standard Treatment Options for Stage IV, Inoperable, and Recurrent Gastric Cancer
Standard treatment options for stage IV, inoperable, and recurrent gastric cancer, including medically or surgically unresectable patients, include the following:
First-line palliative systemic therapy
Standard chemotherapy versus best supportive care for patients with metastatic gastric cancer has been tested in several clinical trials, and there is general agreement that patients who receive chemotherapy live for several months longer on average than patients who receive supportive care.[13,14,15][Level of evidence: 1iiA] During the last 20 years, multiple randomized studies evaluating different treatment regimens (monotherapy vs. combination chemotherapy) have been performed in patients with metastatic gastric cancer with no clear consensus emerging as to the best management approach. A meta-analysis of these studies demonstrated a hazard ratio (HR) of 0.83 for overall survival (OS) (95% confidence interval [CI], 0.74–0.93) in favor of combination chemotherapy.
Evidence (palliative chemotherapy):
Phase II studies evaluating irinotecan-based or oxaliplatin-based regimens demonstrate similar response rates and TTP to those found with ECF or CF, but the former may be less toxic.[20,21,22,23,24,25] There are conflicting data regarding relative efficacy of any one regimen. Ongoing studies are evaluating these newer regimens.
Trastuzumab may be combined with first-line chemotherapy agents in treatment of HER2-positive metastatic gastric adenocarcinomas. HER2 testing is recommended for those with metastatic disease.
Second-line palliative systemic therapy
When patients develop progression of disease after first-line palliative chemotherapy, there is no standard treatment option. Accepted regimens include irinotecan with or without 5-FU/leucovorin, docetaxel, and paclitaxel with or without ramucirumab. (Refer to the Ramucirumab section of this summary for more information.)
Ramucirumab is a fully humanized monoclonal antibody directed against the vascular endothelial growth factor receptor-2.
Ramucirumab is an acceptable treatment in cisplatin- or 5-FU‒refractory, stage IV, gastric cancer.
The combination of paclitaxel and ramucirumab is an acceptable second-line chemotherapy regimen in patients with stage IV gastric or gastroesophageal junction cancer.
Checkpoint inhibitors, particularly programmed death 1 (PD-1) inhibitors, are actively being investigated in the management of gastric and gastroesophageal cancers. Testing for dMMR (IHC staining) or MSI polymerase chain reaction, along with PD-L1 combined positive score (CPS score in the United States) is recommended for patients with metastatic gastric adenocarcinoma.
Second-line treatment for patients with dMMR or MSI-H tumors
Evidence (second-line treatment for patients with dMMR or MSI-H tumors):
Third-line treatment for patients with PD-L1–positive tumors
On the basis of these data, the U.S. Food and Drug Administration has granted pembrolizumab accelerated approval for PD-L1–positive tumors.
On the basis of these data, the Japanese Ministry of Health, Labor, and Welfare approved nivolumab for treatment of advanced gastric cancer that has progressed on previously received chemotherapy.
Treatment Options Under Clinical Evaluation for Stage IV, Inoperable, and Recurrent Gastric Cancer
Treatment options under clinical evaluation for stage IV, inoperable, and recurrent gastric cancer include the following:
Treatment with poly (ADP-ribose) polymerase (PARP) inhibitors and hepatocyte growth factor inhibitors have not shown efficacy at this time.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Editorial changes were made to this summary.
This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of gastric cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewer for Gastric Cancer Treatment is:
Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.
Levels of Evidence
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
Permission to Use This Summary
PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as "NCI's PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary]."
The preferred citation for this PDQ summary is:
PDQ® Adult Treatment Editorial Board. PDQ Gastric Cancer Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/stomach/hp/stomach-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389209]
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Last Revised: 2020-05-07
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