What is the treatment for signet ring cell gastric carcinoma?

Treatment of Signet Ring Cell Gastric Carcinoma

For localized signet ring cell gastric adenocarcinoma, surgery alone with D2 lymphadenectomy is the recommended initial treatment—perioperative chemotherapy provides no survival benefit and worsens outcomes in this specific histologic subtype. 1

Stage-Specific Treatment Algorithm

Very Early Disease (T1a, Intramucosal)

• Endoscopic resection is contraindicated for signet ring cell carcinoma, even for small T1a lesions, because these tumors are characteristically multifocal and occur throughout the stomach, making endoscopic or limited resection inappropriate 1
• This prohibition applies regardless of size or other favorable features that would otherwise qualify non-signet ring cell tumors for endoscopic submucosal dissection 1
• Surgical resection with D2 lymphadenectomy remains necessary even for early-stage disease 1

Localized Resectable Disease (T1b and Higher, Non-Metastatic)

• Surgery alone with D2 lymphadenectomy is the standard treatment—do not use perioperative chemotherapy as it provides no survival benefit and is associated with worse outcomes specifically in signet ring cell histology 1
• This represents a critical departure from the treatment of other gastric adenocarcinoma subtypes, where perioperative chemotherapy (ECF/ECX regimen) is standard for stage IB and above 2
• Complete R0 resection with negative margins is essential, as margin status is a critical prognostic factor 1
• Distal gastrectomy is appropriate for distal tumors; total gastrectomy is required for proximal lesions 1
• A minimum of 14 lymph nodes, optimally at least 25, must be examined pathologically for accurate staging 1

Post-Resection Management

• For pT1aN0 tumors after complete R0 resection, observation without additional adjuvant treatment is recommended 1
• Do not routinely administer adjuvant chemotherapy for completely resected signet ring cell carcinoma, as it does not improve outcomes in this histology 1

Preoperative Staging Requirements

Mandatory Staging Laparoscopy

• Perform laparoscopy with or without peritoneal washings preoperatively in all potentially resectable cases to exclude occult peritoneal metastases, as imaging frequently misses peritoneal disease that would fundamentally change management 1, 2
• This is particularly critical for signet ring cell carcinoma given its propensity for peritoneal spread 1

Additional Staging

• Complete staging workup includes CT of chest, abdomen, and pelvis 2
• HER2 testing should be performed if metastatic disease is documented or suspected, as trastuzumab is indicated for HER2-positive metastatic disease 1

Metastatic or Unresectable Disease

Systemic Chemotherapy

• For unresectable or metastatic disease, systemic chemotherapy based on fluoropyrimidine-platinum combinations is recommended, though response rates are poor in signet ring cell histology 1
• The FDA-approved regimen for gastric adenocarcinoma is docetaxel 75 mg/m² as a 1-hour intravenous infusion, followed by cisplatin 75 mg/m², followed by fluorouracil 750 mg/m² per day as a 24-hour continuous infusion for 5 days, repeated every 3 weeks 3
• Alternative first-line regimens include ECF (epirubicin, cisplatin, fluorouracil) or ECX (epirubicin, cisplatin, capecitabine) 2
• For HER2-positive tumors, add trastuzumab to first-line platinum/fluoropyrimidine doublet chemotherapy 1

Patient Selection

• Palliative chemotherapy should only be offered to patients with adequate performance status 1
• Best supportive care alone is appropriate for patients with poor performance status 1

Hereditary Diffuse Gastric Cancer (CDH1 Mutation)

Prophylactic Surgery

• For patients with CDH1 germline pathogenic variants, prophylactic total gastrectomy between ages 20-30 years is the only effective prevention strategy 1
• D1 lymphadenectomy is recommended as a pragmatic compromise for prophylactic procedures 1
• Baseline endoscopy is mandatory before prophylactic surgery to exclude established cancer requiring neoadjuvant treatment 1

Critical Pitfalls to Avoid

Do Not Use Perioperative Chemotherapy for Localized Disease

• The American College of Surgeons specifically recommends against perioperative chemotherapy for localized signet ring cell gastric adenocarcinoma, as it provides no survival benefit and worsens outcomes 1
• This is the most important distinction from treatment of other gastric adenocarcinoma subtypes 1

Do Not Attempt Endoscopic Resection

• Even for small, early-stage lesions that would otherwise qualify for endoscopic resection, do not attempt endoscopic submucosal dissection, as signet ring cell carcinomas are multifocal 1

Do Not Skip Staging Laparoscopy

• Proceeding to surgery without staging laparoscopy risks missing peritoneal metastases that imaging cannot detect, leading to non-curative resections 1, 2

Do Not Accept Inadequate Lymph Node Evaluation

• Fewer than 14 lymph nodes examined leads to understaging and suboptimal treatment planning 1, 2

Do Not Perform Routine Splenectomy

• Splenectomy should not be performed unless the tumor directly invades the spleen, as it increases postoperative complications without survival benefit 2, 4