What is the treatment approach for gastric invasive adenocarcinoma?

Treatment Approach for Gastric Invasive Adenocarcinoma

The optimal treatment for gastric invasive adenocarcinoma involves surgical resection with appropriate lymphadenectomy, combined with perioperative chemotherapy for most cases beyond stage Ia, as this approach significantly improves 5-year survival rates compared to surgery alone. 1

Initial Staging and Assessment

• Complete staging workup includes physical examination, blood count, liver and renal function tests, endoscopy with biopsy, CT scan of abdomen and pelvis, and chest X-ray or CT of thorax 1
• Endoscopic ultrasound (EUS) helps determine proximal and distal tumor extent, though less useful for antral tumors 1
• Laparoscopy with or without peritoneal washings is recommended for potentially resectable cases to exclude metastatic disease 1, 2
• PET/CT may be useful for detecting occult metastatic disease, though histologic confirmation of PET-avid lesions is recommended 1
• HER2 testing should be performed if metastatic disease is documented or suspected 1, 3

Treatment Planning

Multidisciplinary Approach

• Treatment planning must involve surgeons, medical and radiation oncologists, gastroenterologists, radiologists, and pathologists 1
• Stage should be determined according to the TNM system and AJCC stage grouping 1

Surgical Management

• Surgical resection is the only potentially curative modality for stages I-IV M0 1

• The extent of gastric resection depends on tumor location:

  • Distal gastrectomy for distal tumors when adequate proximal margin can be obtained 1
  • Total gastrectomy for proximal tumors or those along greater curvature of corpus/fundus 1
  • Adequate resection margins: ≥3 cm for Borrmann I-II tumors and ≥5 cm for Borrmann III-IV 1

• Lymphadenectomy recommendations:

  • D2 lymphadenectomy is standard for resectable gastric cancer classified as cT1N+ and cT2-4N-/+ 1
  • At least 14, optimally 25 lymph nodes should be examined pathologically 1
  • Splenectomy is not routinely recommended unless directly involved by tumor 1

Early Stage Disease (T1a)

• For very early gastric cancers (T1a), endoscopic resection may be appropriate if they are well-differentiated, ≤2 cm, confined to mucosa, and non-ulcerated 1, 4
• No additional treatment is necessary for Tis and T1N0 tumors with R0 resection 4

Treatment of Localized Disease (Beyond T1a)

• Perioperative chemotherapy is the standard of care in most of Europe for stage Ib or higher 1:

  • ECF regimen (epirubicin 50 mg/m², cisplatin 60 mg/m², and continuous 5-FU 200 mg/m²/day) given as three cycles pre- and post-operatively significantly improves 5-year survival from 23% to 36.3% 1
  • ECX (epirubicin, cisplatin, capecitabine) is commonly used as an alternative to ECF 1

• Alternative approach (common in the US):

  • Postoperative chemoradiotherapy with 5-FU/leucovorin before, during, and after radiotherapy (45 Gy in 25 fractions) has shown 15% improvement in 5-year overall survival 1

Treatment of Locally Advanced Unresectable Disease

• Concurrent chemoradiotherapy is recommended for patients with unresectable locally advanced gastric cancer with good performance status 1
• Chemotherapy regimens used with radiation include:
  • Capecitabine + paclitaxel
  • Cisplatin + 5-FU/capecitabine/S-1
  • Oxaliplatin + 5-FU/capecitabine/S-1 1
• Re-evaluation for potential surgical resectability should be performed after treatment response 1

Treatment of Metastatic Disease (Stage IV)

• Palliative chemotherapy is recommended for patients with stage IV disease and good performance status 1
• Common regimens include combinations incorporating:
  • Platinum agents (cisplatin, oxaliplatin)
  • Fluoropyrimidines (5-FU, capecitabine, S-1)
  • Anthracyclines (epirubicin)
  • Taxanes (paclitaxel, docetaxel) 1
• For HER2-positive metastatic gastric cancer, trastuzumab in combination with cisplatin and capecitabine or 5-fluorouracil is indicated 3
• For advanced disease that progresses after first-line therapy:
  • Ramucirumab as a single agent or in combination with paclitaxel is approved for patients with disease progression on or after first-line platinum or fluoropyrimidine-based chemotherapy 5

Special Considerations

• Molecular profiling is increasingly important for treatment decisions, with specific subtypes including microsatellite instability-high, Epstein-Barr virus-induced, HER2-positive, and PD-L1-high subtypes potentially benefiting from targeted approaches 6
• Laparoscopic staging should be considered for advanced cases to avoid unnecessary laparotomies in patients with unresectable disease 2
• Patients with poor performance status (ECOG 2) may benefit from best supportive care or palliative interventions to improve nutrition and alleviate symptoms 1

Pitfalls to Avoid

• Inadequate lymph node evaluation (fewer than 14 nodes) may lead to understaging and suboptimal treatment 1
• Omitting laparoscopy in potentially resectable cases may miss peritoneal metastases not detected on imaging 1, 2
• Routine splenectomy increases postoperative complications without survival benefit 1
• Relying solely on CT for staging may miss peritoneal disease, emphasizing the need for comprehensive staging 7, 8