Stomach Cancer Treatment by Stage

Stomach cancer follows a stage ladder more closely than most cancers do. Even so, only two questions really open the conversation.

Can the tumour be removed? And has it spread beyond the stomach and its nearby lymph nodes?

The answers set the shape of the plan. Removable disease is built around an operation, with chemotherapy wrapped around it. Disease that has spread is built around drugs, and the drug choice depends on tests done on the tumour itself.

This page describes the usual options and what decides between them. It is not advice about your own treatment.

Stage 0 means the cancer is confined to the stomach lining. NCI lists surgery and endoscopic mucosal resection as the options.

Endoscopic removal avoids an operation on the stomach. It is not for everyone. NCI describes it for early tumours with good-risk features: Tis or T1a, 2 cm or smaller, mostly well-differentiated, and without ulceration. Those features predict a low chance the cancer has reached lymph nodes.

Careful selection matters, and so does the endoscopist's experience. NCI says close follow-up afterwards should be part of the plan. In a prospective series of 445 people in Tokyo, complete removal was achieved in 278 of 405 people with intramucosal cancer, and disease-free survival was 100 percent at a median 38 months.

Selected stage IA cancers may also be treated this way.

Surgical removal with lymph node clearance is the treatment of choice for stage I disease. Which operation depends on where the tumour sits.

• A distal subtotal gastrectomy is used when the tumour is not in the fundus or near the junction with the oesophagus. NCI reports equivalent survival to total removal, with less illness afterwards.
• A proximal subtotal or total gastrectomy, with removal of part of the oesophagus, is used when the tumour involves the cardia.
• A total gastrectomy is used when the tumour is spread through the stomach, or arises in the body and reaches within 6 cm of the cardia or the far end.

Nearby lymph nodes are removed with every one of these. NCI says the spleen is not removed routinely, and that the value of an extended node dissection is uncertain.

For anything beyond the earliest disease, surgery alone is often not enough. NCI notes the risk of the cancer returning both locally and at a distance is high.

Two approaches have randomised support.

Perioperative chemotherapy means treatment before and after the operation. The AIO-FLOT4 trial randomised 716 people with stage IB to III disease. FLOT is docetaxel, oxaliplatin and fluorouracil with leucovorin, split evenly between the weeks before surgery and the weeks after it. The number of cycles, the interval and the doses are set by your oncology team against your fitness, organ function and how you tolerate the first rounds. Median overall survival was 50 months with FLOT against 35 months with the older ECF or ECX regimen. Margin-free removal was achieved in 85 percent against 78 percent.

The earlier MAGIC trial established the idea using ECF. Five-year overall survival was 36.3 percent with perioperative chemotherapy against 23 percent with surgery alone.

Chemoradiation after surgery is the other approach. With more than 10 years of follow-up, median survival was 35 months against 27 months for surgery alone.

NCI is candid that no randomised trial has compared these two strategies against each other. Which one a team favours can depend on how much surgery has already happened, and on the quality of the node dissection.

For stage I disease with involved nodes or muscle invasion, NCI lists either approach as an option.

Advanced or recurrent stomach cancer is treated with drugs, and the tumour is tested first. NCI says people with metastatic gastric adenocarcinoma should be tested for HER2 amplification, mismatch repair or microsatellite instability status, and the PD-L1 combined positive score.

Claudin 18.2 is the fourth test. It matters because of one drug.

What the current FDA labels support:

• HER2-positive disease. Trastuzumab is approved with chemotherapy for HER2-overexpressing metastatic stomach or gastro-oesophageal junction cancer. Pembrolizumab is approved with trastuzumab and fluoropyrimidine and platinum chemotherapy as first-line treatment when the tumour is HER2-positive and the PD-L1 combined positive score is 1 or more.
• HER2-negative disease. Pembrolizumab is approved with fluoropyrimidine and platinum chemotherapy first-line when the combined positive score is 1 or more. Nivolumab is approved with fluoropyrimidine and platinum chemotherapy for advanced or metastatic disease when PD-L1 is 1 or more.
• Claudin 18.2-positive, HER2-negative disease. Zolbetuximab is approved with fluoropyrimidine and platinum chemotherapy as first-line treatment.

Two notes on where the summary and the labels differ. NCI lists nivolumab with chemotherapy without the PD-L1 requirement now written into the label, and lists it as an option for HER2-positive disease. NCI's list also does not include pembrolizumab as first-line treatment for HER2-negative disease. If you are offered one of these, it is fair to ask which biomarker result supports it.

If chemotherapy alone is used, doublets and triplets are both options. NCI reports a meta-analysis favouring combinations over single drugs, but no clear winner among them.

NCI lists ramucirumab with or without chemotherapy as a second-line option. Its label covers advanced stomach or junction cancer that has progressed after fluoropyrimidine or platinum chemotherapy, alone or with paclitaxel.

Trastuzumab deruxtecan is approved for HER2-positive stomach or junction cancer after a trastuzumab-based regimen. Pembrolizumab is an option for tumours that are mismatch repair deficient or MSI-high.

For a third line, trifluridine with tipiracil is approved after at least two prior lines that included a fluoropyrimidine, a platinum, and either a taxane or irinotecan.

Symptom-directed treatment runs alongside. A stent, laser treatment or a bypass operation can relieve blockage. Radiation can help with bleeding, pain and obstruction.

This is not a side note. The stomach is where eating happens, and every operation on it changes that.

Meals usually become smaller and more frequent. Some people get dumping syndrome, where food moves into the intestine too quickly. After a total gastrectomy, vitamin B12 has to be given for life, because the stomach makes the factor needed to absorb it.

Ask to see a dietitian early. Weight loss during treatment is common and is worth reporting rather than absorbing.

SEER reports five-year relative survival of 39.8 percent for stomach cancer for 2016 through 2022. By stage at diagnosis it is 78.1 percent for localised, 39.0 percent for regional and 8.1 percent for distant disease.

Only 32 percent are found while still localised. Thirty-five percent have already spread. Those figures predate the newest first-line combinations, so they lag behind current treatment.

• Call 911 or go to an emergency department if you vomit blood, or pass black tarry stools, or your abdomen becomes suddenly and severely painful, hard or swollen.
• Ring your cancer team without delay, day or night, if you have a temperature of 100.4°F (38°C) or higher during chemotherapy, or shaking chills. Fever on chemotherapy is a medical emergency, because your white cells may be too low to fight the infection. Do not wait for a call back, and if you cannot reach the team in a few minutes, go to an emergency department and say at once that you are on chemotherapy.
• Call your care team the same day if vomiting stops you keeping fluids down, or you cannot pass gas or stool. Both can mean the stomach or bowel is blocked.
• Call your care team within a day or two if pain is not controlled by your usual medicine, if food starts sticking, or if you are losing weight without trying.

Stomach Cancer, Stomach Cancer Stages, What Does HER2 Status Mean?, and Nutrition During Treatment.

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