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Gastric cancer is the second most common cancer in the world, and Helicobacter pylori infection is the single most important risk factor for gastric cancer. H. pylori is recognized as a class I or definite carcinogen by the World Health Organization (1), and current clinical guidelines from the United States (2), Europe (3), and Asia (4) advocate H. pylori eradication in people at high risk for gastric cancer. However, the efficacy of this approach is unknown, partly because it is uncertain when the cascade of neoplastic changes induced can be halted. Specifically, does H. pylori play an important role in the later stages of neoplastic progression? Recent evidence suggests that other elements of the gastric microbiome are also important in the development of gastric cancer, either as cofactors or as drivers of neoplasia. The article by Li et al. in this issue of the Journal presents new analyses from the Shandong Intervention Trial that shed light on a broader role for antibiotics in the prevention of gastric cancer (5). Randomized clinical trials have shown that antibiotics targeting H. pylori can prevent secondary outcome measures related to gastric cancer. Among patients from a high-risk area in China with precursor lesions, 1 week of antibiotics reduced the rate of progression of intestinal metaplasia compared with placebo (9). Correa et al. randomized adults with precursor gastric lesions to antibiotics vs placebo and demonstrated that regression of metaplasia was proportional to the amount of time spent free of H. pylori infection (10). Furthermore, among patients who underwent endoscopic resection for early gastric cancer, treatment with 1 week of antibiotics reduced risk for metachronous gastric cancer after 3 years of follow-up (11). Finally, a large randomized trial was conducted in Changle County in Fujian Province, China, an area with a remarkably high baseline rate of gastric cancer (150 per 100 000 population) (12). Among 1630 participants with positive H. pylori serologies randomly assigned to 2 weeks of antibiotics vs placebo and actively followed for 7.5 years, there was no statistically significant difference in the incidence of gastric cancer. In a post hoc analysis, the investigators identified a protective effect for antibiotics among those without precursor lesions. This finding led to speculation that H. pylori infection may cause in patients an early " point of no return " —the development of intestinal metaplasia—after which treatment with antibiotics has minimal effect. Well-established animal models of gastric cancer …

Prevention of Gastric Cancer With Antibiotics: Can It Be Done Without Eradicating Helicobacter pylori?