INTRODUCTION — The majority of patients with gastric cancer will require palliative treatment at some point in the course of their disease. Approximately 50 percent of patients already have advanced incurable disease at the time of initial presentation, and even those who undergo potentially curative resection have high rates of distant as well as local recurrence. (See "Surgical management of invasive gastric cancer", section on 'Prognosis'.)
Palliative treatments for advanced gastric cancer can be either local or systemic. While cytotoxic chemotherapy is the most effective treatment modality for patients with metastatic disease, it is frequently inadequate for palliation of local symptoms, such as nausea, pain, obstruction, perforation, or bleeding from a locally advanced or locally recurrent primary tumor, which require multidisciplinary management using endoscopic, surgical, radiotherapeutic, or other approaches. (See "Initial systemic therapy for locally advanced unresectable and metastatic esophageal and gastric cancer".)
Patients with advanced esophagogastric cancer have a high incidence of malnutrition and psychologic distress, both of which may impair survival. All patients with newly diagnosed advanced gastric cancer should have a full assessment of symptom burden, nutritional and psychological status, and social supports as early as possible, ideally, prior to starting systemic chemotherapy. Many patients will benefit from formal palliative care consultation and services. Early referral and initiation of interdisciplinary and palliative care services improve clinical and quality of care outcomes, including survival. (See "Initial systemic therapy for locally advanced unresectable and metastatic esophageal and gastric cancer", section on 'Early supportive care'.)
This topic review will focus on local palliative treatments for patients with locally advanced unresectable or metastatic gastric cancer. Chemotherapy for locally advanced unresectable or metastatic esophageal and gastric cancer is discussed elsewhere, as is endoscopic palliation for dysphagia in patients with locally advanced or recurrent esophageal cancer, and primary surgical treatment. (See "Initial systemic therapy for locally advanced unresectable and metastatic esophageal and gastric cancer" and "Endoscopic palliation of esophageal cancer" and "Surgical management of invasive gastric cancer" and "Surgical management of resectable esophageal and esophagogastric junction cancers".)
THERAPEUTIC OPTIONS FOR LOCAL PALLIATION — For patients with metastatic gastric cancer, therapeutic options to control symptoms of local disease progression, such as nausea, pain, bleeding, and obstruction, include palliative surgical resection, surgical bypass (gastrojejunostomy), radiation therapy (RT), and endoscopic techniques. All forms of palliative therapy must take into account the overall prognosis of the patient in order to avoid excessive morbidity and mortality or lengthy hospital stays in those with a limited life span.
For most patients with obstructive symptoms, we recommend external beam radiation therapy (RT) or endoscopic placement of a stent rather than palliative surgery. For most patients we prefer RT, particularly in instances where there needs to be control of tumor bleeding, because it provides longer term tumor control. (See 'Radiation therapy' below.)
For more immediate relief in a patient where chemotherapy cannot be given concurrently with RT, we prefer placement of an endoscopic stent over RT. Besides a shorter duration of tumor control, stents also can cause increased heartburn and require dietary modifications to avoid stent displacement, which can be difficult for patients. (See 'Endoscopic stent placement' below.)
Palliative surgical bypass (gastrojejunostomy) should be reserved for cases where less invasive methods, such as palliative RT with or without chemotherapy, and endoscopic procedures, such as ablation, stenting, or J-tube placement to establish a route for enteral nutrition, cannot be used. Palliative gastrectomy should be reserved for extreme, highly symptomatic cases where less invasive methods cannot be used. (See 'Palliative resection' below and 'Gastrojejunostomy' below.)
Nonsurgical palliation — A variety of nonsurgical measures have been evaluated for palliation of obstructive symptoms or uncontrolled bleeding, which may be acute or chronic. Medical therapies, such as antacids and H2-antagonists, are often of little benefit. In general, we prefer RT in most circumstances, particularly in instances where there needs to be control of tumor bleeding, because it provides longer term tumor control. For more immediate relief in a patient where chemotherapy cannot be given concurrently with RT, we prefer placement of an endoscopic stent over RT. Besides a shorter duration of tumor control, stents also can cause increased heartburn and require dietary modifications to avoid stent displacement, which can be difficult for patients.
Radiation therapy — External beam RT has a well-defined role in the control of pain, bleeding, or obstruction in patients with localized but unresectable gastric cancer [1-6]. A retrospective review of 115 patients with gastric cancer treated with palliative RT (ranging from 8 Gy in a single fraction to 40 Gy in 16 fractions) revealed that control of bleeding, dysphagia/obstruction, and pain was achieved in 81, 53, and 46 percent of patients, respectively, at one month [6]. Treatment was well tolerated, with only three (2.6 percent) with grade 3 toxicity (nausea, vomiting, and anorexia). Palliation lasted the duration of most patients' lives. There was no difference in response between low (≤39 Gy) and high (>39 Gy) biologically effective dose regimens, although there was a trend toward poorer local control with doses ≤39 Gy.
Three other studies evaluating palliative chemoradiotherapy have also demonstrated durable palliation of dysphagia [2,3], as well as pain and bleeding [7].
There are no controlled studies that directly compare RT or chemoradiotherapy with endoscopic or surgical techniques for symptomatic palliation. However, responses to RT are not as immediate as with stenting or surgical palliation. Furthermore, while control of bleeding may be possible with low RT doses that are not associated with significant side effects [4,5], doses above 40 Gy (which may be associated with significant adverse effects) are often required for palliation of obstruction.
Endoscopic stent placement — For palliation of obstructive symptoms, endoscopic placement of a stent provides a less invasive alternative to surgery for symptom palliation and may possibly be more effective for symptom relief. Published experience with enteral stenting for gastroduodenal obstruction is derived mostly from case series and small comparative trials. The available data suggest that enteral stenting has a similar success rate to surgical palliation (with approximately 90 percent of patients improving clinically) but is associated with less morbidity, procedure-related mortality, and cost. Furthermore, stenting may achieve better quality of life compared with other forms of palliation (such as non-oral feeding through a jejunostomy tube), although they have not been directly compared in controlled trials.
In a review of two randomized trials of endoscopic stenting versus palliative gastrojejunostomy, six comparative studies, and 36 retrospective series, there were no statistically significant differences between the two procedures in terms of efficacy or complications [8]. However, stenting was associated with a trend toward shorter hospital stay, a higher clinical success rate, and faster relief of obstructive symptoms [8]. Patients who received stents did require reintervention more frequently than did surgically treated patients.
This subject is addressed in further detail elsewhere. (See "Enteral stents for the palliation of malignant gastroduodenal obstruction".)
Other endoscopic therapies
Dysphagia — Endoscopic laser treatment can effectively palliate dysphagia due to obstruction in 75 to 93 percent of patients with esophageal or gastric cardia tumors (figure 1) [9-11]. (See "Endoscopic palliation of esophageal cancer".)
Hemorrhage — A variety of endoscopic procedures have been used for the control of tumor-induced hemorrhage; there are no controlled studies to compare their relative efficacy. Laser photocoagulation can be effective, particularly for large tumors with diffuse bleeding, although the equipment is expensive and not widely available [12,13]. An alternative that is being used increasingly is argon plasma coagulation. Another alternative that is available in Canada, Europe, most of Asia, and the United States is endoscopic application of a hemostatic nanopowder (Hemospray) [14]. (See "Argon plasma coagulation in the management of gastrointestinal hemorrhage" and "Overview of the treatment of bleeding peptic ulcers", section on 'Hemostatic sprays'.)
Palliative resection — We recommend against palliative gastrectomy in most patients with advanced gastric cancer who are receiving systemic therapy. Palliative gastrectomy should be reserved for extreme, highly symptomatic cases where less invasive methods cannot be used.
For patients with advanced gastric cancer, the benefits of palliative gastrectomy include rapid symptomatic relief of pain, nausea, bleeding, obstruction, and perforation. In addition, several retrospective reports and a small prospective study conducted in patients with limited metastatic disease suggest that the procedure might be associated with a survival benefit [15-20], although this has not been seen in all studies [21-25]. A significant problem with all of these reports is selection bias; those patients who were candidates for surgical resection may have had a smaller disease burden and a better performance status and prognosis than those who received only a bypass procedure or no surgical intervention at all. Furthermore, most of the reports do not control for other factors that could influence survival, such as use of postoperative systemic chemotherapy [17].
The survival benefit of gastrectomy in patients treated with modern systemic chemotherapy was directly tested in the phase III REGATTA trial, in which 175 patients with advanced gastric cancer and a single noncurable factor confined to the liver, peritoneum, or paraaortic lymph nodes were randomly assigned to chemotherapy alone (S-1 plus cisplatin) or to gastrectomy followed by the same chemotherapy [26]. The study was closed prematurely after an interim analysis suggested that the primary endpoint, overall survival, was not significantly improved by gastrectomy. In the final analysis, two-year survival for chemotherapy alone versus gastrectomy plus chemotherapy was 32 versus 25 percent. Furthermore, patients undergoing gastrectomy had a significantly higher incidence of several serious adverse events related to chemotherapy, including leucopenia, nausea, anorexia, and hyponatremia. Palliative gastrectomy cannot be justified in these patients.
Gastrojejunostomy — In current practice, palliative gastrojejunostomy for patients with metastatic gastric cancer is reserved for cases where less invasive methods, such as palliative RT with or without chemotherapy, and endoscopic procedures, such as ablation, stenting, or J-tube placement to establish a route for enteral nutrition, cannot be used.
Palliative gastrojejunostomy for gastric outlet obstruction associated with unresectable advanced gastric cancer can improve food intake [27]. Multiple case reports and small studies report successful palliation of malignant gastric outlet obstruction using minimally invasive laparoscopic gastrojejunostomy. A small retrospective comparison of patients who had palliative laparoscopic (n = 10) versus open (n = 10) gastrojejunostomy showed a similar mean surgery time but less intraoperative blood loss (23 versus 142 mL) and a shorter length of stay (8 versus 124 days) for the laparoscopically treated group [28]. However, the differences were not statistically significant, likely because of the small sample size.
SPECIAL CONSIDERATIONS DURING THE COVID-19 PANDEMIC — The COVID-19 pandemic has increased the complexity of cancer care. Important issues include balancing the risk from delaying diagnostic evaluation and cancer treatment versus harm from COVID-19, minimizing the number of clinic and hospital visits to reduce exposure whenever possible, mitigating the negative impacts of social distancing on delivery of care, and appropriately and fairly allocating limited health care resources. Many endoscopic and surgical procedures are being postponed or canceled except for emergency situations until the pandemic abates. Specific guidance for decision-making for upper gastrointestinal cancers is available from the Society for Surgical Oncology, European Society for Medical Oncology, and others. General recommendations for cancer care during active phases of the COVID-19 pandemic are discussed separately. (See "COVID-19: Considerations in patients with cancer".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Gastric cancer".)
SUMMARY AND RECOMMENDATIONS
●The majority of patients with gastric cancer will require palliative treatment at some point in the course of their disease. (See 'Introduction' above.)
●Cytotoxic chemotherapy is the most effective treatment modality for metastatic disease but may be inadequate for palliation of local symptoms, such as nausea, pain, obstruction, perforation, or bleeding from a locally advanced or locally recurrent primary tumor. Many patients require multidisciplinary management using endoscopic, surgical, radiotherapeutic, or other approaches. (See 'Therapeutic options for local palliation' above.)
●For patients with obstructive symptoms, we recommend external beam radiation therapy (RT) or endoscopic placement of a stent rather than palliative surgery (Grade 1B). For most patients, we prefer RT, particularly in instances where there needs to be control of tumor bleeding, because it provides longer term tumor control. For more immediate relief in a patient where chemotherapy cannot be given concurrently with RT, we prefer placement of an endoscopic stent over RT. Besides a shorter duration of tumor control, stents also can cause increased heartburn and require dietary modifications to avoid stent displacement, which can be difficult for patients. (See 'Nonsurgical palliation' above.)
RT can control pain, bleeding, and obstruction in patients with localized but unresectable gastric cancer, but responses may be delayed. Furthermore, while control of bleeding may be possible with low RT doses that are not associated with significant side effects, doses above 40 Gy are often required for palliation of obstruction. (See 'Radiation therapy' above and 'Palliative resection' above.)
●Another option to palliate dysphagia due to obstruction in patients with esophageal or gastric cardia tumors is endoscopic laser ablation. (See 'Other endoscopic therapies' above.)
●Given the lack of a survival benefit and the worse chemotherapy-related toxicity, we recommend against palliative gastrectomy for most patients with advanced gastric cancer who are receiving systemic therapy (Grade 1B). Palliative resection should be reserved for extreme, highly symptomatic cases where less invasive methods cannot be used. (See 'Palliative resection' above.)
●In current practice, palliative gastrojejunostomy for patients with metastatic gastric cancer is reserved for cases where less invasive methods, such as palliative RT with or without chemotherapy, and endoscopic procedures, such as ablation, stenting, or J-tube placement to establish a route for enteral nutrition, cannot be used. (See 'Gastrojejunostomy' above.)
