Post-Resection Chemoprevention Tied to Lower Gastric Cancer Risk

Therapy for Helicobacter pylori after endoscopic resection of gastric dysplasia was linked with a reduced risk of gastric cancer and neoplasm occurrence, according to a nationwide cohort study out of South Korea.

About half of the patients were treated post-resection with H. pylori therapy, which consisted either of a proton pump inhibitor (PPI), clarithromycin, and amoxicillin (triple therapy received by 98.4%) or PPI, bismuth, metronidazole, and tetracycline (quadruple therapy done in 13.1%).

Receipt of such therapy was closely tied lower gastric cancer risk for an adjusted hazard ratio (aHR) 0.88 (95% CI 0.80 to 0.96), they reported in Gastroenterology.

H. pylori treatment also significantly cut metachronous gastric neoplasm development (aHR, 0.76, 95% CI 0.70 to 0.82), the authors noted. And the therapy offered "prominent protective effect for late-onset gastric cancer development" in the long term:

• ≥3 years: aHR, 0.84 (95% CI 0.75-0.94)
• ≥5 years: aHR, 0.80 (95% CI 0.68-0.95)

Hong’s group pointed out that "H. pylori is the strongest identified risk factor for gastric cancer, and an estimated 50% of the world’s population is infected with H. pylori. Indeed, persistent H. pylori infection has been reported to be associated with a high rate of recurrence after endoscopic resection," and their findings bolstered the idea of chemoprevention because "receiving eradication therapy reduced the risk of gastric cancer by 12% and metachronous gastric neoplasm by 24%" versus no post-resection treatment.

"More established guidance on the management of gastric dysplasia after endoscopic resection is required," they concluded.

In an editorial accompanying the study, Alexander C. Ford, MBChB, MD, of Leeds Gastroenterology Institute/St. James’s University Hospital in Leeds, England, and David Y. Graham, MD, of Baylor College of Medicine/Michael E. DeBakey Veterans Affairs (VA) Medical Center in Houston, confirmed that the call by Hong’s group for "uniform guidance on the management of gastric dysplasia after endoscopic resection" was reasonably supported by their data.

"However, a broader view is that all countries with a high risk of gastric cancer should consider some form of population-based screening," they advised, such as one-time screening at age 20, followed by contact tracing of infected patients versus a full-scale, population-based screening program.

Stakeholders still seem keen to cast a wide net for screening and prevent H. pylori. For instance, the Asian Pacific Alliance on Helicobacter and Microbiota (APAHAM) gathered in 2020 and came up with 26 consensus statements, including the idea that the "strategy of screen-and-treat for H. pylori infection is most cost-effective in young adults in regions with a high incidence of [gastric cancer] and is recommended preferably before the development of atrophic gastritis and intestinal metaplasia." They also suggested in a Gut article that people ages >50 years may also benefit from screening "integrated or included into national healthcare priorities, such as colorectal cancer screening programs."

Meanwhile, in a 2022 Journal of the Formosan Medical Association article experts in Taiwan touted the success of the population-wide screening program in the Matsu Islands through which the " prevalence of H. pylori infection rapidly declined from 63% to [about] 10% and a reinfection rate of less than 1% per person-year was observed. In 2016, the program resulted in a significant reduction of gastric cancer by 53%. By 2023, fewer than 6 per 100,000 residents will be diagnosed with stomach cancer and by 2025, the incidence and mortality rates will be cut by 68% and 39%, respectively."

The current retrospective study had 69,722 patients (age 62.3 years; 62.8% male), about 30% of whom had diabetes mellitus, 30% hypertension, and about 40% hepatic disease. Hong and co-authors noted that they "verified the occurrence of new-onset gastric cancer and metachronous gastric neoplasm, which encompasses both cancer and dysplasia, >1 year after the index endoscopic resection. Newly diagnosed gastric cancer 3 years and 5 years was regarded as late-onset gastric cancer."

In a 2023 Nature Reviews Clinical Oncology article, Hashem B. El-Serag, MD, MPH, also of the DeBakey VA, and co-authors noted that "other well-established risk factors include excess body fat, cigarette smoking and diets high in salt and processed meats…Epstein–Barr virus infection, autoimmune gastritis and Ménétrier disease," while "possible protective factors include high vegetable intake and treatment with nonsteroidal anti-inflammatory drugs and statins."

A 2023 study in The New England Journal of Medicine found that germline pathogenic variants in nine genes, such as BRCA 1/2 and PALB2, were associated with the risk of gastric cancer. "Furthermore, pathogenic variants and H. pylori infection interacted to markedly increase the risk of gastric cancer in persons with both risk factors," reported Yukihide Momozawa, DVM, PhD, of the RIKEN Center for Integrative Medical Sciences in Yokohama, Japan, and co-authors.

Study limitations included its observational nature and the potential for "healthy user bias," whereby "treated patients who are more health-conscious might exhibit fewer occurrences of gastric cancer, not necessarily due to the preventive effects of H. pylori treatment itself but rather because of other confounding factors," the authors stated. Also, the study was done in a region where there is a higher incidence of gastric cancer, so the results may not apply to other races/ethnicities. Finally, Hong and co-authors did not have data on cigarette smoking, BMI, or genetic risk factors.

The study was supported by the SK Chemical Research Fund of the Korean Society of Gastroenterology and the Soon Chun Hyang University Research Fund.

Hong and co-authors reported no relationships relevant to the contents of this paper to disclose.

Ford reported no relationships relevant to the contents of this paper to disclose.

Graham reported support from the Office of Research and Development Medical Research Service/Department of VA Public Health Service and the NIH/Texas Medical Center Digestive Diseases Center.

Yoo HW, et al "Helicobacter pylori treatment and gastric cancer risk after endoscopic resection of dysplasia: A nationwide cohort study" Gastroenterol 2023; DOI: 10.1053/j.gastro.2023.10.013.

Ford AC, Graham DY "Toward quantification of H. pylori-associated gastric cancer risk: Further evidence supporting development of population-based strategies for H. pylori eradication" Gastroenterol 2023; DOI: 10.1053/j.gastro.2023.10.027.