Gastric Cancer after Helicobacter pylori Eradication: Characteristics, Diagnosis, and Management

Background: Helicobacter pylori eradication is one of the most well-established strategies for the prevention of gastric cancer and is recommended in several countries, particularly in high-risk countries. However, gastric cancer can still develop even after successful eradication. As H. pylori eradication has become more prevalent, the characterization, surveillance, and management strategies for gastric cancers that arise following eradication have emerged as important clinical challenges. Summary: Gastric cancers that develop after H. pylori eradication typically arise in the context of preexisting atrophic gastritis or intestinal metaplasia, high-risk background mucosa rather than obligate precursor lesions, reflecting a field effect that predispose gastric stem cells to malignant transformation. Although H. pylori eradication reduces the overall risk of gastric cancer, residual risk depends on the extent and severity of atrophy or intestinal metaplasia. Molecular changes, including persistent CpG island hypermethylation and aberrant miRNA expression, particularly within intestinal metaplasia, may persist after eradication. These cancers are mainly the intestinal type and frequently present as small, depressed, gastritis-like appearance or lesions covered by epithelium with low-grade atypia, making endoscopic diagnosis challenging. Risk prediction can be improved through endoscopic assessment of precancerous lesions, advanced high-resolution imaging endoscopy techniques, and molecular biomarkers. Given the persistent risk, individualized, risk-based long-term surveillance strategies are recommended, particularly for patients with extensive atrophy or intestinal metaplasia. Key Messages: (1) Despite H. pylori eradication, the risk of gastric cancer persists in patients with atrophic mucosal changes and intestinal metaplasia. (2) Gastric cancers after H. pylori eradication exhibit distinct endoscopic and pathological features compared to those without prior eradication, making early diagnosis challenging. (3) Risk stratification based on endoscopic assessment, advanced imaging, and molecular biomarkers can refine surveillance strategies, emphasizing the importance of long-term, personalized follow-up after eradication.