Treatment requires both appropriate systemic therapy and an operation that provides an R0 resection with adequate lymphadenectomy.
Perioperative therapy
For resectable gastric and gastroesophageal junction adenocarcinoma, durvalumab plus FLOT is now an approved perioperative option and produced better event free survival than FLOT alone.
FLOT every 14 days:
- Docetaxel 50 mg/m² IV
- Oxaliplatin 85 mg/m² IV
- Leucovorin 200 mg/m² IV
- Fluorouracil 2600 mg/m² continuous infusion over 24 hours
Four FLOT treatments are given before surgery and four after surgery.
For patients weighing at least 30 kg:
Durvalumab 1500 mg IV every 4 weeks with perioperative chemotherapy for up to four durvalumab cycles, followed by durvalumab 1500 mg IV every 4 weeks for up to ten additional cycles.
Availability and regulatory approval vary by country.
FLOT without immunotherapy remains a valid perioperative regimen where durvalumab is unavailable or inappropriate.
Surgery
Siewert I: usually treated with transthoracic oesophagectomy and mediastinal plus upper abdominal lymphadenectomy.
Siewert III: generally treated as gastric cancer with total gastrectomy, distal oesophageal resection and appropriate perigastric lymphadenectomy.
Siewert II: the operation is individualised according to tumour extension. Transthoracic oesophagectomy is favoured when oesophageal involvement and mediastinal nodal risk dominate. Extended total gastrectomy with distal oesophagectomy may be appropriate when disease is predominantly gastric and an adequate proximal margin can be achieved.
The objective is anatomical, not semantic: achieve an R0 resection while removing the lymphatic basin at greatest risk.
Metastatic or unresectable disease requires biomarker directed systemic therapy. Test adenocarcinoma for HER2, PD L1, MSI or mismatch repair deficiency and relevant additional targets.
