Stomach cancer surgery

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Fahad Hasan, M.D.[2] Parminder Dhingra, M.D. [3] Mohammed Abdelwahed M.D[4]

Surgery remains the only potentially curative treatment for stomach cancer and is central to the multidisciplinary management of gastric cancer. Endoscopic resection is the treatment of choice for early gastric cancer meeting absolute or expanded indication criteria, as defined by the Japanese Gastric Cancer Association (JGCA) 2021 (6th edition) treatment guidelines.^[1] Methods for endoscopic resection include endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). Side effects of endoscopy include bleeding and perforation. For T1 tumors, a gross resection margin of 2 cm should be obtained. A proximal margin of at least 3 cm is recommended for T2 or deeper tumors with an expansive growth pattern and 5 cm for those with an infiltrative growth pattern. For tumors invading the esophagus, a 5-cm margin is not necessarily required, but intraoperative frozen section examination of the resection line is preferred to confirm an R0 resection.

Lymph node dissection is defined by extent. D1 lymphadenectomy refers to dissection of only the perigastric lymph nodes (stations 1-7). D1+ lymphadenectomy adds stations 8a, 9, and (for total gastrectomy) 11p to the D1 dissection and is used for cT1 tumors not indicated for D1 alone. D2 lymphadenectomy is an extended lymph node dissection that additionally removes nodes along the hepatic, left gastric, celiac, and splenic arteries, and, when indicated, the splenic hilum; it is the standard of care for potentially curable T2-T4 tumors. D3 (super-extended) dissection adds D2 plus removal of nodes within the porta hepatis and para-aortic regions; prophylactic para-aortic dissection added to D2 did not improve survival in the randomized JCOG9501 trial and is not routinely recommended outside clinical trials.^[2]

Laparoscopic and robot-assisted minimally invasive gastrectomy with D2 lymphadenectomy are now supported by long-term randomized data as oncologically equivalent, and in some outcomes superior, alternatives to open gastrectomy for both early and locally advanced gastric cancer.^[3][4][5] For resectable locoregional adenocarcinoma (cT2 or higher, or node-positive), perioperative systemic chemotherapy with FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) — now increasingly combined with the anti-PD-L1 monoclonal antibody durvalumab — has replaced older anthracycline-based (ECF/MAGIC) regimens as the perioperative standard of care.^[6][7] For metastatic disease, gastrectomy is not routinely recommended for palliation alone, based on the randomized REGATTA trial, and first-line systemic therapy — chemotherapy plus the anti-PD-1 monoclonal antibody nivolumab in appropriate candidates — is preferred over surgery-first approaches.^[8][9]

Before proceeding to surgery, gastric cancer must be distinguished from other benign and malignant conditions that can produce a similar gastric mass, ulceration, or wall thickening on endoscopy or computed tomography.

• Early gastric cancer is an invasive gastric cancer that invades no more than the submucosa whatever the lymph node metastasis condition (T1 and any N).
• Endoscopic resection is the preferred treatment for lesions meeting absolute or expanded indication criteria (below); surgical gastrectomy with lymphadenectomy remains standard for lesions outside these criteria or after non-curative endoscopic resection.
• Long-term oncologic outcomes after appropriately-indicated, curative endoscopic resection are comparable to primary surgical resection.^[10]

Endoscopic indications are now categorized as absolute or expanded, per the JGCA 2021 (6th edition) guidelines and the 2023 ASGE guideline, superseding the earlier single size-cutoff criteria used in most Western practice.^[1][11]

Absolute indication (endoscopic resection is curative if pathology confirms an eCura A result, with no need for additional surgery):

• Differentiated-type intramucosal (cT1a) adenocarcinoma without ulceration, regardless of size
• Differentiated-type intramucosal (cT1a) adenocarcinoma with ulceration, ≤3 cm in diameter

Expanded indication (endoscopic resection is acceptable, but curability must be confirmed pathologically using the eCura scoring system):

• Undifferentiated-type intramucosal (cT1a) adenocarcinoma without ulceration, ≤2 cm in diameter^[12]

The ASGE similarly suggests ESD over EMR for well- or moderately-differentiated, non-ulcerated intestinal-type early gastric adenocarcinoma measuring 20-30 mm, and either ESD or EMR for lesions <20 mm.^[11]

The following are the different types of endoscopic resection techniques for gastric cancer:^[13]

• Endoscopic mucosal resection (EMR):
  • The lesion and the surrounding mucosa are lifted by submucosal injection of saline and removed using a steel snare.
• Endoscopic submucosal dissection (ESD):
  • The mucosa surrounding the lesion is incised using a high-frequency electric knife.
  • ESD is more likely to result in complete (en bloc) resection of early gastric cancer, and is now the preferred technique over EMR for most lesions meeting expanded indication, but requires more time and endoscopic skill.

• Bleeding^[14]
• A tumor size of more than 4 cm is a risk factor for acute bleeding.
• Antithrombotic drug therapy is a risk factor for delayed bleeding.
• Bleeding treatment is injection therapy, electrocoagulation, ligation with a detachable snare, and endoscopic clipping.

• Perforation rate for ESD is 4.5 percent, compared with 1.0 percent for EMR.^[15]
• Tumor location in the upper stomach and size more than 2 cm have been associated with an increased risk of perforation with ESD.
• Treatment of a perforation is endoscopic clipping, or open or laparoscopic surgery in case of failed clipping.

Historically, curative endoscopic resection required en bloc removal of a lesion meeting all of the following:^[16]

• En bloc resection
• Tumor size ≤2 cm
• Differentiated histology
• Depth of invasion ≤T1a
• Negative horizontal margin
• Negative vertical margin
• No lymphatic or vascular invasion

This binary framework has largely been superseded by the eCura system, a validated scoring tool that stratifies patients after ESD into risk categories using tumor size, depth of invasion, lymphovascular invasion, and horizontal/vertical margin status: eCura A and B denote curative or near-curative resection appropriate for surveillance alone, while eCura C-1 (met size/depth criteria but positive horizontal margin only) and eCura C-2 (all other non-curative resections, carrying a substantially higher risk of lymph node metastasis) generally warrant consideration of additional gastrectomy with lymphadenectomy in medically fit patients.^[17] The eCura system allows individualized decision-making, particularly in elderly or frail patients in whom the operative risk of completion gastrectomy may outweigh the absolute risk of occult nodal metastasis.

• There is no single mandated approach for eCura C-1/C-2 resections; the decision balances the estimated risk of residual lymph node metastasis against operative risk.^[17]
• Completion gastrectomy with standard lymph node dissection is generally recommended for eCura C-2 resections in patients fit for surgery.^[18]
• Occult lymph node metastasis is identified in a minority of patients who undergo completion gastrectomy and lymph node dissection after non-curative resection; risk varies by eCura subcategory and underlying histologic risk factors rather than being a fixed rate for all non-curative resections.^[17]

• Patients with only positive lateral (horizontal) margins can be managed with repeat endoscopic therapy rather than surgery (eCura C-1).
• Almost 90 percent of lateral positive margins were followed endoscopically with no recurrences.
• Patients with positive vertical margins, submucosal invasion beyond criteria, or lymphovascular invasion (eCura C-2) are generally treated with completion surgery.

Local mucosal recurrence after EMR/ESD for tumors that had fulfilled the criteria for indication for endoscopic resection may be treated by another ESD.^[20]

• Annual endoscopy with abdominal ultrasonography or CT scan follow-up is recommended.
• Helicobacter pylori should be tested for and treated (eradication therapy reduces metachronous gastric cancer risk).

• Closer endoscopic and cross-sectional imaging surveillance is warranted; residual or recurrent disease may be treated with repeat endoscopic coagulation (laser or argon-plasma coagulation) or surgery as appropriate.

Surgical management of a gastric tumor with resection of adjacent lymph nodes, integrated with perioperative systemic therapy, presents the best chance for long-term survival in invasive gastric cancer.

• Diagnostic upper endoscopy with biopsy, followed by locoregional staging with endoscopic ultrasonography and computed tomography of the chest, abdomen, and pelvis; PET-CT and diagnostic staging laparoscopy (with peritoneal washings/cytology) are used selectively to exclude occult metastatic disease before committing a patient to curative-intent surgery.
• Tumor tissue should be tested for HER2 overexpression/amplification, PD-L1 combined positive score, microsatellite instability/mismatch-repair status, and, where relevant, claudin 18.2 expression, as these biomarkers guide selection of perioperative and later-line systemic therapy.
• Cases should be reviewed in a multidisciplinary tumor board (surgery, medical oncology, radiation oncology, gastroenterology, and pathology) before initiating treatment, per current NCCN and JGCA guidance.^[1]
• For tumors of the esophagogastric junction, Siewert classification and the 2023 Upper GI Oncology Summit consensus guide the choice between esophagectomy and gastrectomy-based approaches.^[21]

• For resectable, locally advanced adenocarcinoma (generally cT2 or higher, or clinically node-positive), perioperative FLOT (fluorouracil, leucovorin, oxaliplatin, docetaxel) improved 5-year overall survival compared with anthracycline-based ECF/ECX and is preferred over surgery-alone or older MAGIC-type regimens.^[6]
• The addition of the anti-PD-L1 agent durvalumab to perioperative FLOT (MATTERHORN trial) significantly improved event-free survival (hazard ratio 0.71) and pathologic complete response (19.2% vs 7.2%) compared with FLOT alone, and is now an FDA-approved perioperative option for resectable gastric and gastroesophageal junction adenocarcinoma.^[7]
• For unresectable locally advanced or metastatic disease, first-line chemotherapy plus the anti-PD-1 agent nivolumab (CheckMate 649) improved overall survival and progression-free survival compared with chemotherapy alone, with the greatest benefit in tumors with a high PD-L1 combined positive score.^[9]
• HER2-positive metastatic disease is treated with trastuzumab-based regimens added to chemotherapy (± immunotherapy), per current NCCN and JGCA recommendations.^[1]
• Gastrectomy added to chemotherapy does not improve survival in patients with a single non-curable factor (REGATTA trial: 2-year overall survival 25% with gastrectomy plus chemotherapy vs 32% with chemotherapy alone) and should not be performed for palliative intent alone outside of symptom control.^[8]

• Standard gastrectomy: Two-thirds of the stomach is resected; it is the principal surgical procedure used.
• Non-standard gastrectomy: The extent of gastric resection and lymphadenectomy is altered according to tumor stage.
• Modified surgery: The extent of gastric resection and lymphadenectomy is reduced compared with standard surgery (e.g., for favorable early tumors not meeting endoscopic resection criteria).
• Extended surgery: Gastrectomy with resection of adjacent involved organs, or with extended lymphadenectomy.

• Palliative surgery: Palliative gastrectomy or gastrojejunostomy, selected according to resectability and surgical risk, to relieve bleeding or obstruction; reserved for symptoms not controllable by endoscopic or radiologic means, given the lack of survival benefit shown in REGATTA.^[8]
• Reduction surgery: Aims to prolong survival by reducing tumor volume; evidence for a survival benefit is weak and this is not routinely recommended.

• Total gastrectomy: Resection of the entire stomach, including the cardia and pylorus.
• Distal gastrectomy: Resection including the pylorus; the cardia is preserved.
• Pylorus-preserving gastrectomy: Resection preserving the upper third of the stomach and the pylorus with a portion of the antrum.
• Proximal gastrectomy: Resection including the cardia; the pylorus is preserved.
• Segmental gastrectomy: Circumferential resection preserving the cardia and pylorus.
• Local resection
• Non-resectional surgery (bypass surgery, gastrostomy, and jejunostomy)

• For T1 tumors, a gross resection margin of 2 cm should be obtained.
• A proximal margin of at least 3 cm is recommended for T2 or deeper tumors with an expansive growth pattern and 5 cm for those with an infiltrative growth pattern.
• For tumors invading the esophagus, a 5-cm margin is not necessarily required, but intraoperative frozen section examination of the resection line is preferred to confirm an R0 resection.
• When the tumor border is unclear, preoperative endoscopic marking with clips based on biopsy mapping helps define the resection line.

• The standard surgical procedure is total or distal gastrectomy, increasingly performed by a minimally invasive (laparoscopic or robotic) approach when technically feasible (see below).
• Pancreaticosplenectomy: Pancreatic invasion by tumor requires total gastrectomy regardless of tumor location.
• Total gastrectomy with splenectomy: Considered for tumors along the greater curvature with metastasis to station 4 lymph nodes; routine prophylactic splenectomy is otherwise avoided due to increased morbidity without proven survival benefit.
• Esophagectomy and proximal gastrectomy: Considered for adenocarcinoma located on the proximal side of the esophagogastric junction, per Siewert classification.^[21]
• Pylorus-preserving gastrectomy: For tumors in the middle third of the stomach with the distal tumor border at least 4 cm proximal to the pylorus.
• Vagal nerve preservation: Preservation of the hepatic branch of the anterior vagus and the celiac branch of the posterior vagus improves postoperative quality of life by reducing post-gastrectomy gallstone formation, diarrhea, and weight loss; in pylorus-preserving gastrectomy the hepatic branch is preserved to maintain pyloric function.
• Omentectomy: Removal of the greater omentum is usually integrated into standard gastrectomy for T3 or deeper tumors; for T1/T2 tumors, omentum more than 3 cm from the gastroepiploic arcade may be preserved.
• Bursectomy:^[22] removal of the inner peritoneal surface of the bursa omentalis; avoided in T1/T2 tumors to prevent injury to the pancreas and adjacent blood vessels, but shows a modest survival benefit in T3/T4a tumors.

• Laparoscopic distal gastrectomy with D2 lymphadenectomy is non-inferior to open surgery for locally advanced gastric cancer, with fewer early (15.7% vs 23.4%) and late (4.7% vs 9.5%) complications; long-term individual-patient-data meta-analysis of KLASS-02 and CLASS-01 shows comparable overall survival (82.7% vs 83.3%) and recurrence-free survival (76.9% vs 77.9%) between laparoscopic and open approaches.^[3][4][5]
• A randomized phase 2 trial of robotic versus laparoscopic distal gastrectomy reported a 3-year disease-free survival of 85.8% with robotic surgery versus 73.2% with laparoscopic surgery, alongside less blood loss and more retrieved lymph nodes with the robotic approach; confirmatory phase III data (JCOG1907/MONA LISA) are awaited.^[23]
• Adding complete mesogastric excision to D2 lymphadenectomy (D2+CME) improved 3-year disease-free survival compared with conventional D2 dissection alone in the randomized DCGC01 trial, without a statistically significant difference in overall survival.^[24]
• Laparoscopic sentinel node navigation surgery for stomach preservation did not meet the pre-specified non-inferiority margin for 3-year disease-free survival compared with standard laparoscopic gastrectomy in the SENORITA trial, although 5-year overall and disease-free survival did not differ significantly between groups; routine adoption outside of expert centers and clinical trials is not currently recommended.^[25]

• One of the most debated areas in the surgical management of gastric cancer is the optimal extent of lymph node dissection.^[26]
• The draining lymph nodes for the stomach are divided into 16 stations by the JGCA classification; stations 1 to 6 are perigastric, and the remaining stations lie adjacent to major vessels, behind the pancreas, and along the aorta.^[27]

D1 lymphadenectomy

• Dissection of only the perigastric lymph nodes (stations 1-7).
• Indicated for T1a tumors that do not meet criteria for EMR/ESD and for T1bN0 tumors that are histologically differentiated and 1.5 cm or smaller in diameter, without lymphovascular invasion.

D1+ lymphadenectomy

• D1 plus stations 8a, 9, and (for total gastrectomy) 11p.
• Indicated for cT1 tumors not meeting criteria for D1 dissection alone.

D2 lymphadenectomy

• Extended lymph node dissection, including removal of nodes along the hepatic, left gastric, celiac, and splenic arteries, as well as the splenic hilum when indicated.
• Standard of care for potentially curable T2-T4 tumors and whenever nodal involvement is suspected.

D3 (super-extended) dissection

• D2 plus removal of nodes within the porta hepatis and para-aortic regions.
• Prophylactic para-aortic dissection added to D2 did not improve overall survival in the randomized JCOG9501 trial and is not routinely recommended.^[2]

• Therapeutic options to control symptoms of local disease progression — nausea, pain, bleeding, and obstruction — include palliative surgical resection, surgical bypass (gastrojejunostomy), radiation therapy, and endoscopic techniques.
• Palliative resection: Palliative gastrectomy should be reserved for highly symptomatic cases where less invasive methods cannot be used, given the absence of a survival benefit over chemotherapy alone shown in the REGATTA trial.^[8][28]
• Gastrojejunostomy: Palliative gastrojejunostomy for gastric outlet obstruction associated with unresectable advanced gastric cancer can improve food intake and is reserved for cases where less invasive methods cannot be used.^[29]
• Endoscopic stent placement:^[30] a less invasive alternative to surgery for symptom palliation of obstruction, with comparable efficacy and complication rates to palliative gastrojejunostomy in randomized comparisons, and possibly better short-term quality of life.
• Endoscopic hemostatic/ablative therapy: Laser photocoagulation or argon plasma coagulation can be effective for control of tumor-related bleeding, particularly for large tumors with diffuse bleeding.^[31]

Total gastrectomy

• Roux-en-Y esophagojejunostomy^[32]
• Jejunal interposition
• Double tract method

Distal gastrectomy

• Billroth I gastroduodenostomy^[33]
• Billroth II gastrojejunostomy
• Roux-en-Y gastrojejunostomy
• Jejunal interposition

Pylorus-preserving gastrectomy^[34]

• Gastro-gastrostomy
• Proximal gastrectomy
• Esophagogastrostomy
• Jejunal interposition
• Double tract method

• Surveillance after curative-intent gastrectomy typically includes history and physical examination every 3-6 months for the first 1-2 years, then every 6-12 months up to 5 years; cross-sectional imaging (CT) and laboratory studies (including complete blood count and vitamin B12/iron levels) are performed at intervals guided by risk of recurrence.^[1]
• Surveillance endoscopy is performed periodically to evaluate the anastomosis and remnant stomach (if present) and to screen for metachronous gastric cancer.
• Nutritional support, including monitoring for and treatment of vitamin B12 deficiency, iron deficiency, osteoporosis, and dumping syndrome, is an essential component of long-term post-gastrectomy care.
• Helicobacter pylori eradication should be confirmed, as persistent infection increases the risk of metachronous gastric neoplasia after both endoscopic and surgical resection.

• Elderly and frail patients: Endoscopic resection and, when surgery is required, less extensive lymphadenectomy or minimally invasive approaches may be preferred to reduce operative morbidity; outcomes of EMR and gastrectomy for early gastric cancer in elderly patients are comparable to those in younger patients when appropriately selected.^[10]
• HER2-positive and microsatellite instability-high/mismatch-repair-deficient tumors: Biomarker-directed therapy (anti-HER2 or immune checkpoint

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