Gastric Cancer: Symptoms, Types, Causes and Treatment

Gastric cancer, or stomach cancer, remains a significant global health challenge despite advances in detection and treatment. Its often subtle onset and diverse presentation make early diagnosis difficult, contributing to poor outcomes in many cases. By understanding the symptoms, types, causes, and available treatments, patients and caregivers can better navigate this complex disease. This article synthesizes the latest research to provide a comprehensive, human-centered overview of gastric cancer.

Symptoms of Gastric Cancer

Gastric cancer symptoms can be elusive, overlapping with many benign gastrointestinal conditions. Many patients first notice vague digestive complaints, while others experience more alarm-specific symptoms as the disease progresses. Recognizing and interpreting these symptoms early can be life-saving, but it's not always straightforward for patients or clinicians.

Symptom	Description	Prognostic Value	Sources
Dyspepsia	Indigestion, discomfort	Common, non-specific	1 2 3
Fatigue	Persistent tiredness	Common, especially early	2 5
Weight Loss	Unintentional loss	Poor prognosis	1 5
Dysphagia	Difficulty swallowing	Advanced disease	1 2
Vomiting	Nausea, vomiting episodes	Less prognostic value	1 3 5
Abdominal Mass	Palpable lump	Advanced disease	1
GI Bleeding	Blood in vomit/stool	Variable significance	1

Table 1: Key Symptoms

Symptom Overview

Early vs. Late Symptoms

• Early Symptoms: In the initial stages, gastric cancer may cause mild indigestion, heartburn, or a sense of fullness after eating small amounts. These symptoms are easily mistaken for routine digestive issues, making early detection challenging. Fatigue and persistent tiredness are also frequently reported but are often overlooked or misattributed to lifestyle factors 2 3.
• Alarm Symptoms: As cancer advances, more concerning symptoms may appear, such as significant unintentional weight loss, persistent vomiting, difficulty swallowing (dysphagia), and the presence of a palpable abdominal mass. These so-called "alarm symptoms" are strongly associated with a worse prognosis and often signal advanced, possibly inoperable disease 1 5.

Symptom Clusters and Experience

Patients typically experience multiple symptoms simultaneously, often fluctuating in intensity. The burden is especially high in advanced or metastatic disease, where tiredness and loss of appetite dominate the clinical picture. Co-occurring symptoms and their management become a central focus in improving quality of life 3 4 5.

Patient Perception and Delayed Diagnosis

Misinterpretation or normalization of symptoms, such as attributing heartburn or tiredness to stress or diet, can delay medical consultation. Many patients only seek help when symptoms persist, worsen, or significantly disrupt daily life—a factor contributing to late diagnosis and limited treatment options 2.

Types of Gastric Cancer

Gastric cancer is not a single disease but a collection of subtypes with distinct biological behaviors, prognoses, and treatment responses. Understanding these types is crucial for personalized care and guiding therapy.

Type	Key Features	Prognosis	Sources
Intestinal Adenocarcinoma	Gland-forming, linked to chronic gastritis	Moderate	7 9 14
Diffuse Adenocarcinoma	Poorly cohesive, aggressive	Poor	7 8 10
Proximal (Cardia)	Origin near gastroesophageal junction	Variable	7 9
Distal (Non-cardia)	Lower stomach, linked to H. pylori	Variable	7 9

Table 2: Main Types of Gastric Cancer

Histological Subtypes

Intestinal Type

• Characteristics: Resembles intestinal glandular tissue, usually forms gland-like structures. It often follows a sequence of precancerous changes, known as Correa's cascade, starting with chronic inflammation and progressing through stages such as atrophy and intestinal metaplasia 7.
• Epidemiology: More common in older adults and regions with a higher prevalence of Helicobacter pylori infection.
• Prognosis: Generally better than the diffuse type, partly due to a more predictable growth pattern and earlier detection 7 14.

Diffuse Type

• Characteristics: Characterized by poorly cohesive cancer cells that infiltrate the stomach wall, leading to thickening without forming a discrete mass. This type includes signet ring cell carcinoma.
• Behavior: More aggressive, occurs at a younger age, and has a higher recurrence rate and poorer prognosis 7 8 10.
• Molecular Features: Associated with specific genetic mutations (e.g., CDH1) and unique proteomic signatures, offering potential targets for novel therapies 8 10.

Anatomical and Molecular Classifications

• Proximal (Cardia) vs. Distal (Non-cardia): Gastric cancers are also classified by their location in the stomach. Proximal cancers arise near the gastroesophageal junction and may represent a different clinical entity compared to distal cancers, which are more often linked to environmental and infectious risk factors 7 9.
• Molecular Subtypes: Recent advances in genomics have identified four molecular subtypes (mesenchymal-like, microsatellite unstable, TP53-active, TP53-inactive), each with distinct clinical outcomes and treatment implications. For example, microsatellite-unstable tumors tend to have better prognosis and may respond differently to immunotherapy 6 10 19.

Causes of Gastric Cancer

The development of gastric cancer results from a complex interplay between environmental exposures, infections, lifestyle choices, and genetic predisposition. Understanding these causes is essential for prevention and risk reduction.

Cause Category	Specific Example	Strength of Evidence	Sources
Infection	Helicobacter pylori	Strong	7 11 12
Diet	High salt, low fruit/vegetable	Strong	7 11 13 18
Lifestyle	Smoking, alcohol	Strong	7 11 15
Genetics	Family history, genetic syndromes	Moderate-Strong	7 11 14

Table 3: Leading Causes and Risk Factors

Key Risk Factors

Helicobacter pylori Infection

• Role: Chronic infection with H. pylori is the single most significant risk factor for gastric cancer, especially for non-cardia types. The bacterium induces chronic inflammation, leading to a cascade of precancerous changes in the stomach lining 7 12.
• Mechanisms: Certain bacterial strains, host genetics, and environmental factors can amplify the carcinogenic risk. H. pylori can directly interact with and reprogram gastric epithelial cells, activating pathways linked to cancer development 12.

Diet and Nutrition

• High Salt Intake: Diets high in salted, smoked, or pickled foods increase risk, especially when combined with H. pylori infection.
• Low Fruit and Vegetable Intake: Lack of dietary antioxidants and micronutrients may promote carcinogenesis 7 11 18.
• Other Dietary Factors: Nitrites and nitrates in processed meats, as well as certain food preservatives, have also been implicated.

Lifestyle and Environmental Exposures

• Smoking: Cigarette smoking significantly increases gastric cancer risk, with the risk rising with duration and quantity of smoking. Importantly, risk decreases after smoking cessation, approaching that of non-smokers after about 10 years 15.
• Alcohol: Heavy alcohol use may contribute, though the association is less robust than with smoking.

Genetics and Family History

• Inherited Syndromes: A small percentage of gastric cancers arise due to inherited gene mutations (e.g., hereditary diffuse gastric cancer from CDH1 mutations) 7 14.
• Family History: Individuals with a first-degree relative with gastric cancer are at higher risk, underlining the role of genetic susceptibility and shared environmental factors 11 14.

Other Factors

• Demographics: Incidence increases with age, with a median diagnosis age of 70. However, about 10% of cases occur in those 45 or younger, often linked to genetic factors 14.
• Occupational and Environmental Exposures: Certain industrial exposures and ionizing radiation have been identified as risk factors in epidemiological studies 11.

Treatment of Gastric Cancer

Treatment for gastric cancer depends on the stage at diagnosis, tumor location and subtype, and patient-specific factors. A multidisciplinary approach—combining surgery, chemotherapy, radiotherapy, targeted therapies, and supportive care—offers the best chance for improved outcomes. However, the prognosis remains poor in advanced cases, highlighting the importance of early detection.

Stage/Type	Main Treatment	Key Points	Sources
Early, localized	Endoscopic/surgical resection	Curative in early cases	7 17 18
Locally advanced	Surgery + perioperative chemo	Improves survival	17 18 19
Advanced/metastatic	Chemotherapy, targeted, palliative	Median survival <1 year	16 17 18 19 20
HER2-positive	Trastuzumab + chemo	Improved outcomes	16 18 19 20
Symptom management	Palliative/supportive care	Quality of life focus	3 4 5 18

Table 4: Treatment Strategies by Stage and Type

Curative Approaches

Early-Stage Disease

• Endoscopic Resection: For very early cancers confined to the mucosa or superficial submucosa, endoscopic removal can be curative, especially in countries with robust screening programs.
• Surgery: Surgical removal of the tumor with adequate lymph node dissection (D2 lymphadenectomy) remains the cornerstone for localized disease 7 17 18.
• Adjuvant/Perioperative Chemotherapy: Chemotherapy before and after surgery (perioperative) or after surgery (adjuvant) can reduce recurrence and improve survival in stage 1B or higher cancers 18 19.

Advanced and Metastatic Disease

• Chemotherapy: Systemic chemotherapy is the mainstay of treatment for advanced or metastatic disease. Doublet regimens (platinum plus fluoropyrimidine) are standard first-line, with sequential lines used as disease progresses. Combination regimens offer modest survival benefits over single agents but increase side effects 16 17 18 19 20.
• Targeted Therapies: For tumors overexpressing HER2, trastuzumab (a monoclonal antibody) combined with chemotherapy significantly improves survival. Ramucirumab (anti-angiogenic) and immune checkpoint inhibitors (nivolumab, pembrolizumab) are options in certain cases, particularly in later lines of therapy and specific molecular subtypes 16 18 19 20.
• Radiotherapy: May be used in select cases for local control or symptom relief, often as part of a combined modality approach.

Multidisciplinary and Supportive Care

• Personalized Therapy: Molecular classification (e.g., microsatellite instability, HER2, PD-L1 expression) is increasingly guiding therapy choices and clinical trial eligibility 6 10 19.
• Symptom Management: Addressing the high burden of symptoms such as pain, fatigue, and appetite loss is essential, especially in advanced disease. Supportive care, including nutritional support, palliative interventions, and psychosocial support, is a critical aspect of comprehensive treatment 3 4 5 18.

Research and Future Directions

• Immunotherapy and Novel Agents: Ongoing research is focused on harnessing the immune system and developing molecularly targeted drugs tailored to specific subtypes 8 10 19 20.
• Prevention: Eradication of H. pylori and lifestyle modifications (smoking cessation, healthy diet) can reduce risk and are essential public health strategies 7 12 13 15.

Conclusion

Gastric cancer remains a formidable health challenge worldwide, particularly due to its late presentation and biological diversity. However, advances in understanding its symptoms, types, causes, and treatment options offer hope for improved outcomes.

Key Takeaways:

• Symptoms are often vague and easily overlooked—persistent digestive complaints, weight loss, and fatigue warrant medical attention, especially in at-risk individuals.
• Gastric cancer encompasses multiple types, each with distinct behaviors and responses to therapy.
• Major causes include H. pylori infection, diet, smoking, and genetics—many of which are modifiable.
• Treatment is stage-dependent, with curative options for early disease but a continued emphasis on palliation and quality of life in advanced cases.
• A personalized, multidisciplinary approach, guided by molecular subtyping and patient needs, is the new standard of care.

Early recognition, prevention strategies, and continued research into targeted therapies and immunotherapy are crucial steps toward reducing the global burden of gastric cancer.