Adenocarcinoma of the stomach; H. pylori-driven; often diagnosed late with poor prognosis.
Also known as: gastric cancer, stomach cancer, gastric adenocarcinoma
Overview
Malignant neoplasm of the stomach, predominantly adenocarcinoma (>90%). Lauren classification: intestinal type (well-differentiated, glandular, associated with H. pylori/atrophic gastritis) and diffuse type (poorly cohesive, signet-ring cells, linitis plastica, hereditary CDH1 mutation in some).
Epidemiology
~27,000 new cases and ~11,000 deaths annually in the US. Worldwide, 5th most common cancer; high incidence in East Asia, Eastern Europe, and Latin America. 5-year survival ~33% (US); >60% in countries with screening (Japan, South Korea).
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Older adult with new dyspepsia, weight loss, and iron-deficiency anemia.
Differential diagnosis
Peptic ulcer disease — Benign ulcers can mimic; biopsy ALL gastric ulcers; repeat EGD to confirm healing
Gastric lymphoma (MALT or DLBCL) — H. pylori association; biopsy with immunohistochemistry; MALT may regress with H. pylori treatment
GIST (gastrointestinal stromal tumor) — Submucosal mass; KIT/PDGFRA+; biopsy via EUS; treat with imatinib
Functional dyspepsia — Normal EGD; same symptoms; diagnosis of exclusion
Gastroparesis — Early satiety, vomiting undigested food; gastric emptying study
Pancreatic cancer (with gastric outlet obstruction) — Painless jaundice, weight loss; pancreatic mass on CT
Diagnostic workup
Diagnostic criteria
Histologic confirmation on biopsy. HER2, MMR/MSI, PD-L1 testing on all advanced/metastatic cases to guide systemic therapy. Staging by AJCC 8th edition TNM.
Labs
CBC (microcytic anemia)
BMP, LFTs, albumin
H. pylori testing
CEA, CA 19-9, CA 72-4 — not diagnostic; may aid in surveillance
Imaging
Upper endoscopy with biopsy — diagnostic; multiple biopsies of any ulcer or mass
Endoscopic ultrasound (EUS) — accurate T and N staging; allows FNA of lymph nodes
CT chest/abdomen/pelvis with contrast — staging, metastases
PET-CT — selected cases; useful for detecting distant disease
Diagnostic laparoscopy with peritoneal washings — recommended for T3/T4 or node-positive disease before definitive therapy (10-30% have occult peritoneal disease)
Diagnostic algorithm
Lauren Subtype
Intestinal
Diffuse
Histology
Well-differentiated glands
Poorly cohesive, signet-ring cells
Distribution
Sporadic, regional clusters
More uniform global incidence
Precursor
H. pylori → atrophic gastritis → metaplasia → dysplasia
Often de novo; CDH1 mutation in hereditary
Age
Older
Younger
Sex
Male > female
Equal
Prognosis
Better
Worse (linitis plastica)
Pattern
Mass lesion
Diffuse infiltration
Lauren classification of gastric adenocarcinoma — intestinal vs diffuse type.
Treatment
First-line
Multidisciplinary management
H. pylori eradication if present
Stage-directed treatment (see by_subtype)
Early gastric cancer (T1a, well-differentiated, non-ulcerated, <2 cm)
Endoscopic submucosal dissection (ESD) — curative in carefully selected lesions
Surveillance EGD
Locally advanced (T2-T4 or node-positive)
Perioperative chemotherapy with FLOT (5-FU/leucovorin/oxaliplatin/docetaxel) × 4 cycles before and after surgery — current standard (FLOT4 trial)
Total or subtotal gastrectomy with D2 lymphadenectomy
Adjuvant chemoradiation (capecitabine + RT) — alternative for patients who did not receive neoadjuvant therapy (MAGIC/INT-0116)
Biopsy ALL gastric ulcers — 4% are malignant; repeat EGD in 8-12 weeks to confirm healing.
H. pylori eradication reduces gastric cancer risk; effect strongest when treated before atrophic gastritis or metaplasia develops.
FLOT regimen replaced ECF as preferred perioperative chemotherapy for resectable disease (FLOT4 trial).
HER2-positive metastatic gastric cancer benefits from trastuzumab — test all advanced cases.
Diagnostic laparoscopy detects peritoneal disease missed by CT in 10-30% of locally advanced cases.
Linitis plastica (diffuse infiltration) carries the worst prognosis and is typically not amenable to curative resection.
Hereditary diffuse gastric cancer (CDH1 mutation): consider prophylactic total gastrectomy in carriers.
Japan/Korea perform screening EGD due to high prevalence; not cost-effective in low-incidence US population.
References
NCCN 2024 — NCCN Guidelines Version 2.2024 — Gastric Cancer
FLOT4 — Al-Batran SE et al. Perioperative chemotherapy with FLOT versus ECF/ECX for resectable gastric or GEJ adenocarcinoma. Lancet 2019;393:1948-1957
ToGA Trial — Bang YJ et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or GEJ cancer. Lancet 2010;376:687-697
MAGIC Trial — Cunningham D et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. NEJM 2006;355:11-20
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