Treatment of gastric cancer is decided by the stage at diagnosis and by the tumour’s biology, and it is planned by a multidisciplinary team because the options — endoscopy, surgery, chemotherapy, radiotherapy, targeted drugs and immunotherapy — are combined differently at each stage. Two questions organise the decisions: can the tumour be removed completely, and which molecular markers make a systemic drug worth adding?
Endoscopic resection of early cancer
A cancer confined to the mucosa (Tis or T1a) that is small, no more than 2 cm in diameter, of predominantly differentiated type and without ulceration carries a low risk of lymph node spread. In that setting the lesion can be removed endoscopically, by endoscopic mucosal resection or endoscopic submucosal dissection, and the patient avoids a gastrectomy. Careful selection according to these criteria, an experienced endoscopist and surveillance afterwards are all part of the treatment.
Surgery
For cancers that cannot be removed endoscopically, surgery is the main curative treatment: partial (subtotal) or total gastrectomy together with removal of the regional lymph nodes. The extent of resection follows the location of the tumour. A distal tumour is treated by distal subtotal gastrectomy. A tumour involving the cardia is treated by proximal subtotal gastrectomy or total gastrectomy, together with a length of esophagus, because these tumours often spread along the submucosal lymphatics of the esophagus. A tumour that involves the stomach diffusely is treated by total gastrectomy. The spleen is not removed routinely.
The extent of lymph node dissection is debated. A D2 dissection, which clears the nodes along the major arteries supplying the stomach, is standard in Japan and Korea. In Western practice the survival benefit is less certain and the operation carries more morbidity, particularly in less experienced hands.
Treatment around surgery
For a tumour that invades the muscularis propria or has involved lymph nodes but can still be removed, chemotherapy given before and after surgery — perioperative chemotherapy — improves survival compared with surgery alone, so it is the usual approach. Two alternatives are used in different regions: postoperative chemoradiation, used particularly in North America, and adjuvant chemotherapy alone after a D2 gastrectomy, used in East Asia. Because most patients relapse from distant disease, it is the systemic treatment around surgery that reduces that risk.
Advanced and metastatic disease
When the cancer cannot be removed or has already spread, treatment is palliative: it relieves symptoms and lengthens survival but does not cure. Chemotherapy is the backbone, and the drugs added to it are chosen by the tumour’s markers. Trastuzumab is added for tumours that overexpress HER2. The immune checkpoint inhibitors nivolumab and pembrolizumab are added for tumours that are PD-L1 positive or mismatch repair deficient (MSI-high). Zolbetuximab targets CLDN18.2-positive tumours. In later lines of treatment, ramucirumab, alone or with chemotherapy, and trastuzumab deruxtecan for HER2-positive disease are options.
When the tumour obstructs the stomach or bleeds, treatment can also be local: endoluminal stent placement, endoluminal laser therapy, or a gastrojejunostomy to bypass an obstruction; radiotherapy to control bleeding, pain or obstruction; or, in selected patients, palliative resection.
Biomarker testing
Because these drugs are chosen by marker, a patient with advanced gastric adenocarcinoma should have the tumour tested for HER2 amplification, for mismatch repair deficiency or microsatellite instability, and for PD-L1 expression, with CLDN18.2 testing where the drug is available. These markers are the reason the routine evaluation of the tumour includes molecular assessment.