Gastric Adenocarcinoma

Gastric adenocarcinoma is the dominant gastric malignancy and arises from the glandular mucosa.

Lauren histology broadly separates intestinal and diffuse patterns. Diffuse cancers, including poorly cohesive and signet ring phenotypes, infiltrate the gastric wall and have a greater tendency toward peritoneal dissemination.

Linitis plastica represents diffuse infiltrative involvement producing a rigid poorly distensible stomach.

Curative management requires adequate local resection and treatment of micrometastatic disease.

Progressive weight loss, early satiety, epigastric discomfort, iron deficiency anaemia and anorexia are common.

Distal tumours may cause gastric outlet obstruction. Proximal tumours may produce dysphagia.

Occult peritoneal spread can occur despite relatively unimpressive CT findings, particularly with diffuse or poorly cohesive disease.

Upper gastrointestinal endoscopy with multiple biopsies: establish histology and tumour location.

CT chest, abdomen and pelvis: determine regional and distant disease.

Staging laparoscopy with peritoneal cytology: important before perioperative treatment in resectable locally advanced disease and particularly with cT3 or cT4, node positive or poorly cohesive cancers.

Endoscopic ultrasound is most useful for early lesions when deciding between endoscopic resection and surgery.

Early gastric cancer

Selected superficial mucosal cancers with a very low risk of lymph node metastasis can undergo endoscopic submucosal dissection.

The resected specimen must be assessed for:

• Depth of invasion
• Differentiation
• Ulceration
• Lymphovascular invasion
• Horizontal and vertical margins

Noncurative endoscopic pathology requires surgical gastrectomy with lymphadenectomy in a fit patient.

Resectable locally advanced disease

For most fit patients with T2 or greater or node positive resectable adenocarcinoma, perioperative systemic therapy is appropriate.

A standard FLOT regimen every 14 days is:

• Docetaxel 50 mg/m² IV
• Oxaliplatin 85 mg/m² IV
• Leucovorin 200 mg/m² IV
• Fluorouracil 2600 mg/m² continuous IV infusion over 24 hours

Four cycles are given before surgery and four after surgery when tolerated. Perioperative FLOT improved median overall survival compared with older epirubicin based regimens.

A current option for resectable gastric adenocarcinoma is the addition of:

Durvalumab 1500 mg IV every 4 weeks during perioperative FLOT, followed after surgery by 1500 mg IV every 4 weeks for up to ten additional cycles. This reduced recurrence and improved event free survival compared with FLOT alone.

Surgery

The operation is determined by tumour position.

Distal cancer: distal subtotal gastrectomy is preferred when an adequate oncological proximal margin can be achieved. It provides equivalent oncological control with less morbidity than total gastrectomy in appropriately selected distal disease.

Diffuse, proximal or extensive disease: total gastrectomy is usually required.

Perform appropriate regional lymphadenectomy. D2 lymphadenectomy is the standard oncological dissection in experienced centres.

Routine splenectomy is not required unless the tumour directly involves the spleen or splenic hilar clearance is specifically necessary.

After total gastrectomy, reconstruct with Roux en Y oesophagojejunostomy.

Postoperative nutritional consequences include weight loss, iron deficiency, vitamin B12 deficiency, calcium and vitamin D deficiency and dumping symptoms. Lifelong vitamin B12 replacement is required after total gastrectomy.

Metastatic disease

Test advanced adenocarcinoma for:

• HER2
• PD L1 combined positive score
• MSI or mismatch repair deficiency
• CLDN18.2 where available

These biomarkers determine whether treatment includes HER2 targeted therapy, immune checkpoint therapy or CLDN18.2 directed therapy.

A malignant outlet obstruction can be treated with endoscopic stenting, endoscopic gastroenterostomy or surgical gastrojejunostomy depending on performance status and expected survival.

Operate in metastatic disease only for a defined indication such as perforation, uncontrolled bleeding or obstruction not adequately controlled by less invasive measures.