Stomach Cancer Symptoms, Stages and Treatment – Patient Guide

What Are Stomach and Gastroesophageal Junction Cancer?

Stomach cancer (gastric adenocarcinoma) is a cancer arising from the glandular cells lining the inner surface of the stomach, and accounts for approximately %95 of stomach cancers. Adenocarcinomas developing where the esophagus and stomach meet (gastroesophageal junction, GEJ) belong to the same biological family, but are addressed with their own classification and treatment nuances — this guide covers both comprehensively. The past three years have seen successive new FDA approvals at an unprecedented pace in the treatment of this disease group: new biomarkers (Claudin 18.2), new antibody-drug conjugates, perioperative immunotherapy and, most recently (August 25, 2026), a completely new targeted therapy-immunotherapy combination for HER2-positive disease have been approved. This guide discusses every detail, from the causes and diagnosis of the disease to staging and the most current treatment options.

Three main axes determine the treatment approach in stomach cancer: the tumor's location (gastroesophageal junction or stomach body — distinguished by the "Siewert classification"), its stage (early/resectable or metastatic) and its molecular profile (HER2, Claudin 18.2, microsatellite instability, PD-L1 status). Particularly in metastatic disease, which biomarker is positive now directly determines which drug will be used — therefore, the staging and treatment sections of this guide are structured around this molecular framework.

Stomach Anatomy

The stomach is a digestive organ in the upper abdominal cavity, between the esophagus and the duodenum, the first part of the small intestine. It consists of four main regions: the cardia, where the esophagus opens into the stomach; the dome-shaped fundus above the cardia; the corpus (body), the largest part of the stomach, where food is stored and digested; and the antrum/pylorus, opening into the small intestine.

From inside to outside, the stomach wall consists of the mucosa (the inner lining containing glandular cells — the vast majority of adenocarcinomas start here), submucosa, muscularis propria (muscle layer) and, outermost, the subserosa/serosa layers. This layered structure forms the basis of staging by tumor depth (T category).

While the stomach mechanically mixes food and breaks it into small pieces, it also chemically initiates protein digestion by secreting hydrochloric acid and the enzyme pepsin; its acidic environment also acts as a barrier against harmful microorganisms.

How Common Is It? (Current Statistics)

Risk Factors

• Helicobacter pylori infection (the most important risk factor)
• Smoking (RR ~1,61)
• High-salt food consumption (RR ~1,55)
• Processed/red meat consumption
• Low fruit and vegetable consumption
• Chronic atrophic gastritis and pernicious anemia (RR ~6,8)
• Previous gastric surgery (long-term risk of gastric stump cancer)
• Epstein-Barr virus (EBV) infection (a distinct molecular subtype of stomach cancer)
• Obesity
• Chronic gastroesophageal reflux (GERD) — particularly for cardia/GEJ cancers

Hereditary Stomach Cancer Syndromes

A small proportion of stomach cancers (approximately %1-3) are associated with hereditary syndromes; however, recognizing them is crucial because the risk in these patients is often very high.

Histological and Molecular Classification

Lauren Classification: Intestinal and Diffuse Types

Described in 1965 (Laurén P., Acta Pathologica Microbiologica Scandinavica, 1965), this classic histological classification divides gastric adenocarcinoma into two main biological behaviors:

TCGA Molecular Subtypes

According to the comprehensive molecular analysis by The Cancer Genome Atlas (TCGA) consortium (Nature, 2014), gastric adenocarcinoma is divided into four molecular subtypes: EBV-positive (%9 — associated with Epstein-Barr virus, characterized by high PD-L1 expression), microsatellite unstable (MSI) (%22), genomically stable (%20 — associated with diffuse histology and RHOA mutations) and chromosomally unstable (CIN) (%50 — the most common subtype, associated with amplifications in receptor genes such as HER2). Although this classification matters in research, current clinical treatment decisions rely more on the targetable biomarkers described below.

Symptoms

• Indigestion (dyspepsia) and upper abdominal discomfort
• Difficulty swallowing (particularly in GEJ/cardia tumors)
• Early satiety after eating a small amount of food
• Unexplained weight loss
• Nausea and vomiting
• Anemia (low blood count) and associated fatigue
• Black/tarry stools or occult bleeding (due to chronic blood loss)
• In advanced stages: abdominal swelling (ascites), jaundice, palpable lymph nodes

Early-stage stomach cancer usually causes no obvious symptoms; therefore, it is important to consult a physician promptly when the symptoms above appear — particularly in people over 50, with a history of H. pylori or a family history. These symptoms can also arise from many benign causes other than stomach cancer, but must be assessed for differential diagnosis.

How Is It Diagnosed?

Endoscopy and Biopsy

Upper gastrointestinal endoscopy is the gold standard for diagnosing stomach cancer; a thin, flexible camera directly visualizes the inner surfaces of the stomach, esophagus and duodenum, and suspicious areas undergo biopsy for pathological examination. After the diagnosis is confirmed, a second endoscopy/biopsy may be needed for surgical planning.

Imaging for Staging

Contrast-enhanced computed tomography (CT) (chest, abdomen, pelvis) is the main imaging method for assessing local tumor spread and possible distant metastases. Endoscopic ultrasonography (EUS) is more sensitive than CT for assessing tumor depth in the stomach wall (T stage) and surrounding lymph nodes. In suspicious cases, PET-CT may contribute to screening for distant metastases.

Biomarker (Molecular) Tests

Testing four biomarkers that directly guide treatment selection is now considered standard for every patient diagnosed with metastatic stomach/GEJ cancer:

Staging: The TNM System (AJCC 8. Edition)

T Category

N and M Categories

N0: no regional lymph node metastasis. N1: metastases in 1-2 regional lymph nodes. N2: metastases in 3-6 regional lymph nodes. N3a: metastases in 7-15 regional lymph nodes. N3b: metastases in 16 or more regional lymph nodes. M0: no distant metastasis. M1: distant metastasis present (including distant lymph nodes or peritoneal spread).

Stage Groups

Treatment Planning: A Multidisciplinary Approach

Stomach/GEJ cancer treatment is planned by a multidisciplinary team of surgeons, medical oncologists, radiation oncologists, gastroenterologists, pathologists and dietitians. Three main questions determine treatment decisions: (1) Is the tumor resectable (can it be completely removed surgically)? (2) Is the disease localized/locally advanced or metastatic? (3) What is the tumor's HER2, Claudin 18.2, MSI and PD-L1 status ? The answers to these three questions determine the treatment steps discussed in detail below.

Surgical Treatment

Endoscopic Resection: For Very Early Stages

For tumors confined to the most superficial layer of the stomach wall with a very low risk of lymph node involvement (typically T1a, meeting certain size/histology criteria), the tumor can be removed from the stomach wall through an endoscope. Two techniques are used for this: Endoscopic Mucosal Resection (EMR) and, preferred for larger/deeper lesions, Endoscopic Submucosal Dissection (ESD). This approach offers curative treatment while preserving the entire stomach.

Gastrectomy

For most early and locally advanced stomach cancers, standard curative surgery removes the tumor, the diseased part of the stomach and regional lymph nodes (gastrectomy). Depending on tumor location and spread, options include total gastrectomy (the entire stomach), subtotal/partial gastrectomy (part of the stomach, with reconstruction of the digestive tract) or proximal/distal gastrectomy ; surgery can be performed using an open or laparoscopic (minimally invasive) technique.

Lymph Node Dissection: D1 and D2

According to the Japanese Gastric Cancer Association (JGCA) classification, lymphadenectomy accompanying gastrectomy is classified by the stations it includes: D1 (perigastric stations), D1+ (stations additional to D1 — used for early-stage tumors not meeting endoscopic resection criteria) and D2 (in addition to D1, includes stations along the left gastric, common hepatic, celiac and splenic arteries). For curative surgery, current NCCN and JGCA guidelines define the standard approach as D2 lymphadenectomy; it should be performed in experienced centers by specialist surgeons.

Palliative Surgical Procedures: Managing Obstruction

In advanced or unresectable disease, if tumor-related gastric outlet obstruction develops, stomach contents can be diverted to the small intestine by gastrojejunostomy (open or laparoscopic). During this procedure, nutritional support may require a tube placed directly into the stomach through the abdominal skin, a gastrostomy tube (G-tube) , or a tube placed in the small intestine, a jejunostomy tube (J-tube) ; today, endoscopic stent placement is also a frequently preferred, less invasive alternative for relieving obstruction.

Systemic Treatment in Early-Stage and Locally Advanced (Resectable) Disease

Because patients with MSI-high tumors may derive a different degree of benefit from chemotherapy, neoadjuvant chemotherapy is assessed case by case within the multidisciplinary team. Adjuvant radiotherapy (alone or combined with chemotherapy) may also be considered in selected patients with insufficient lymph node removal or inadequately clear surgical margins.

First-Line Treatment in Metastatic Stomach/GEJ Cancer

Treatment selection in metastatic disease is now almost entirely determined by biomarker results. The pathway below directs patients to different treatment arms according to HER2 status, followed by Claudin 18.2 and PD-L1/MSI status.

Note: Overall survival benefit was statistically significant only in the triple combination (zanidatamab+tislelizumab+chemotherapy) arm; the rate of grade ≥3 adverse events was higher with the triple combination (%71,8) than in the other two arms (%59,0 and %59,5). This approval was granted only one day before this guide was prepared and is an extremely recent development.

Second- and Later-Line Treatment in Metastatic Stomach/GEJ Cancer

Treatment-Related Side Effects and Their Management

Chemotherapy (FLOT Components and Others)

Agents such as 5-fluorouracil/capecitabine, oxaliplatin, docetaxel, cisplatin and irinotecan can cause class-typical side effects such as nausea and vomiting, bone marrow suppression (neutropenia, anemia, thrombocytopenia), mucositis, diarrhea, hand-foot syndrome and peripheral neuropathy. Blood counts are monitored regularly, effective preventive drugs are used for nausea, and signs of peripheral neuropathy (tingling or numbness in the hands/feet) must be reported to the physician.

Targeted Therapies

Trastuzumab and zanidatamab require monitoring of cardiac function before treatment and at regular intervals (risk of cardiac toxicity). Ramucirumab is associated with hypertension, proteinuria and increased bleeding risk; blood pressure should be monitored regularly. Trastuzumab deruxtecan carries a drug class-specific risk of interstitial lung disease/pneumonitis — developing a cough or shortness of breath requires urgent assessment. Zolbetuximab is frequently associated with nausea and vomiting; these side effects are usually more pronounced during initial infusions and are managed with prophylactic antiemetics.

Immunotherapy (Nivolumab, Pembrolizumab, Tislelizumab)

Checkpoint inhibitors carry a risk of "immune-related adverse events" due to the immune system attacking its own tissues (colitis, hepatitis, pneumonitis, thyroid dysfunction and other endocrine disorders, skin reactions). These side effects can usually be managed well when recognized and treated early; however, because some may be serious/life-threatening, any new symptom (diarrhea, jaundice, cough/shortness of breath, extreme fatigue) must be reported immediately.

Long-Term Effects After Gastrectomy

Dumping syndrome (early/late symptoms due to food passing too quickly into the small intestine), B12 and iron deficiency (requiring regular monitoring and supplementation when needed), adverse effects on bone health and weight loss are common long-term problems after gastrectomy. Small, frequent meals; avoiding drinking fluids with meals; a diet high in protein/fiber and low in simple sugars; and regular dietitian follow-up are the main management approaches.

FDA Approval History: The Accelerating Revolution in Stomach/GEJ Cancer Treatment

Diagnosis, Licensing and Reimbursement in Türkiye

No records were found in Turkish drug databases (TİTCK product codes, price list) for zolbetuximab (Vyloy), zanidatamab (Ziihera) or tislelizumab (Tevimbra); these three drugs are considered unlicensed in Türkiye and therefore not covered by SGK, at least as of the date this guide was prepared — particularly as not even a day has passed since FDA approval of the zanidatamab+tislelizumab combination, this is an expected outcome. Because current licensing and reimbursement status can change quickly, direct checks of TİTCK and SGK's official sources are recommended before treatment decisions.

Frequently Asked Questions

Are stomach cancer and a stomach ulcer the same?

No. A stomach ulcer is a benign sore, usually due to H. pylori or painkiller use; however, because some ulcer-like lesions may actually be cancer, nonhealing or recurrent ulcers must be assessed by biopsy.

What is the difference between stomach cancer and gastroesophageal junction (GEJ) cancer?

Both can be adenocarcinomas, but the precise tumor location (Siewert classification) affects the surgical approach and some treatment decisions; GEJ tumors can be treated with esophageal or stomach cancer protocols according to location.

Is everyone with metastatic stomach cancer now given the same chemotherapy?

No. Today, patients are assigned to different biomarker-directed treatment arms according to HER2, Claudin 18.2, PD-L1 and MSI status; therefore, performing these tests in every patient diagnosed with metastatic disease is crucial.

There is a family history of stomach cancer. Am I at risk too?

A family history can increase stomach cancer risk; particularly if stomach cancer occurred at a young age or in multiple close relatives, genetic counseling and testing may be recommended for syndromes such as hereditary diffuse gastric cancer (CDH1). It is important to share your family history with your doctor in detail.

How can very recently approved drugs such as zanidatamab+tislelizumab be accessed in Türkiye?

Such a recently approved treatment generally takes time to enter the licensing and reimbursement process in Türkiye. You are advised to confirm the current situation directly with your physician or TİTCK/SGK's official sources, and ask about clinical trials you may qualify for.