What is the treatment for signet ring cell gastric carcinoma?

Treatment of Signet Ring Cell Gastric Carcinoma

Critical First Principle: Avoid Perioperative Chemotherapy in Localized Disease

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

This represents a fundamental departure from standard gastric adenocarcinoma management and is the most important clinical decision point.

Stage-Based Treatment Algorithm

Very Early Disease (T1a, Intramucosal)

• Endoscopic submucosal dissection (ESD) is NOT recommended for signet ring cell carcinoma, even for small lesions. 1
• These lesions are characteristically multifocal and occur throughout the stomach, making endoscopic or limited resection inappropriate. 1
• This contradicts some older literature suggesting ESD may be acceptable for selected early signet ring cell cases—the guideline position is clear that multifocal disease risk precludes endoscopic approaches. 1

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

Surgical resection with D2 lymphadenectomy is the definitive treatment. 1

Preoperative Staging Requirements:

• Perform staging laparoscopy with or without peritoneal washings in all potentially resectable cases to exclude occult peritoneal metastases that imaging frequently misses. 1, 2
• This step is mandatory—proceeding to surgery without laparoscopy risks discovering unresectable disease intraoperatively. 1

Surgical Principles:

• Complete R0 resection with negative margins is the critical prognostic factor. 1
• Distal gastrectomy is appropriate for distal tumors; total gastrectomy is required for proximal lesions. 1
• D2 lymphadenectomy must be performed, removing perigastric nodes and nodes along celiac arterial branches. 1, 2
• A minimum of 14 lymph nodes, optimally at least 25, must be examined pathologically for accurate staging. 1
• Do not perform routine splenectomy unless the tumor directly invades the spleen—it increases complications without survival benefit. 2, 3

Postoperative Management:

• For pT1aN0 tumors after complete R0 resection, observation without additional adjuvant treatment is recommended. 1
• Do not administer adjuvant chemotherapy for localized signet ring cell carcinoma—this differs from other gastric adenocarcinoma subtypes where perioperative chemotherapy improves outcomes. 1

Locally Advanced Unresectable Disease

• Concurrent chemoradiotherapy is recommended for patients with good performance status (ECOG 0-1). 2, 3
• Chemotherapy regimens include capecitabine + paclitaxel, cisplatin + fluoropyrimidine (5-FU/capecitabine/S-1), or oxaliplatin + fluoropyrimidine given concurrently with radiation. 2
• Re-evaluate for potential surgical resectability after treatment response. 2

Metastatic or Unresectable Disease (Stage IV)

Systemic chemotherapy based on fluoropyrimidine-platinum combinations is recommended for patients with adequate performance status, though response rates are poor in signet ring cell histology. 1

First-Line Chemotherapy Options:

• Docetaxel 75 mg/m² + cisplatin 75 mg/m² + fluorouracil 750 mg/m²/day × 5 days, repeated every 3 weeks. 4
• Alternative regimens include ECF (epirubicin, cisplatin, 5-FU) or ECX (epirubicin, cisplatin, capecitabine). 2

HER2 Testing:

• Perform HER2 testing on all metastatic cases—if HER2-positive, add trastuzumab to platinum/fluoropyrimidine doublet chemotherapy. 1, 2

Performance Status Considerations:

• Best supportive care alone is appropriate for patients with poor performance status (ECOG ≥2). 1
• Palliative chemotherapy should only be offered to patients with adequate performance status. 1

Hereditary Diffuse Gastric Cancer (CDH1 Germline Mutations)

• 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 give perioperative chemotherapy for localized signet ring cell carcinoma—this is associated with worse outcomes compared to surgery alone. 1
• Do not attempt endoscopic resection even for small, early lesions—multifocal disease is characteristic and will be missed. 1
• Do not proceed to surgery without staging laparoscopy—imaging misses peritoneal metastases in a significant proportion of potentially resectable cases. 1, 2
• Do not accept inadequate lymph node evaluation (fewer than 14 nodes examined)—this leads to understaging and suboptimal treatment planning. 1, 2
• Do not perform routine splenectomy—it increases morbidity without oncologic benefit. 2, 3

Prognostic Considerations

• Early-stage signet ring cell carcinoma (T1a-T1b) has favorable prognosis when completely resected, with lower lymph node metastasis rates than other poorly differentiated gastric cancers. 5
• However, advanced signet ring cell carcinoma has significantly worse prognosis than other gastric adenocarcinoma subtypes. 6
• Pretreatment endoscopic biopsy showing signet ring cells accurately predicts final histology (92.5% accuracy) and independently predicts poor prognosis in advanced disease. 7