Incidence of new gastric cancers cut in half after H. pylori treatment

By Robyn Boyle, RPh, for MDLinx
Published April 12, 2018

Key Takeaways

Patients with early gastric cancer who received treatment for Helicobacter pylori had lower rates of subsequent gastric cancer than patients who received placebo, according to a prospective study published in the New England Journal of Medicine.

The study was led by Il Ju Choi, MD, PhD, from the National Cancer Center in Goyang, South Korea. The research team set out to determine if H. pylori treatment prevents metachronous cancer and decreases histologic changes in patients with early gastric cancer.

Endoscopic resection, which preserves the stomach, is indicated for early gastric cancers that are not at risk for lymph-node metastasis. Patients with gastric cancer usually have advanced precancerous changes in gastric mucosa, including glandular atrophy and intestinal metaplasia, on histologic analysis. Results from prior studies evaluating the effectiveness of H. pylori treatment in healthy patients without precancerous changes are inconsistent.

Patients between 18 and 75 years of age with histologically differentiated early gastric cancer or high-grade adenoma (confirmed on endoscopic biopsy) who were scheduled for endoscopic resection were eligible for the study. Inclusion criteria included current H. pylori infection, endoscopic localization of a mucosal tumor without ulceration, and no lymph-node or distant-organ metastasis.

Participants were randomly assigned to receive either H. pylori eradication therapy or placebo. Treatment included amoxicillin 1,000 mg plus clarithromycin 500 mg plus the proton-pump inhibitor rabeprazole 10 mg twice daily for seven days. The placebo group received rabeprazole 10 mg plus placebo pills. Rabeprazole was maintained in both groups for an additional four weeks to promote ulcer healing.

Participants underwent endoscopic evaluation at three, six, and 12 months, then every six or 12 months until the last enrolled patient reached the 3-year follow-up. If H. pylori infection was detected at the closeout endoscopic examination, patients received quadruple therapy for ten days with a proton-pump inhibitor, bismuth, metronidazole, and tetracycline.

Endoscopic biopsy specimens for histologic evaluation of glandular atrophy and intestinal metaplasia were obtained from the gastric antrum lesser, corpus lesser, and corpus greater curvature at baseline, at three months, and at 36 months after randomization.

H. pylori infection status was determined by a rapid urease test on samples obtained from the corpus greater curvature and by Wright–Giemsa staining of biopsy specimens from the three predefined sites. The WHO classification system was used for histologic classification of gastric cancer. Suspicion of invasive carcinoma or higher was considered to be indicative of definite gastric cancer; carcinoma in situ was considered to be an adenoma.

Primary outcomes included the incidence of metachronous gastric cancer, defined as a gastric cancer detected on endoscopy at the 1-year follow-up or later, and the improvement from baseline of at least one grade of glandular atrophy at the corpus lesser curvature at the 3-year follow-up.

Secondary outcomes included the incidence of metachronous adenoma and the overall survival rate, defined as the interval between the initiation of a trial medication and the date of death from any cause or end of study.

A total of 396 patients were included in the modified intention-to-treat analysis population (194 in the treatment group and 202 in placebo group). Demographic and tumor characteristics were similar in the two groups.

During a median follow-up of 5.9 years, metachronous gastric cancer developed in 7.2% in the treatment group and in 13.4% in the placebo group (hazard ratio [HR]: 0.50; P=0.03).

The second primary outcome was analyzed in 327 patients who had biopsy specimens at the 3-year follow-up. The proportion of patients who had an improved grade of atrophy in the corpus lesser curvature was higher in the treatment group than in the placebo group (48.4% vs 15.0%, P < 0.001).

The odds ratio (OR) for improvement was 5.30 in the treatment group compared with the placebo group.

In addition, the proportion of patients who had an improved grade of intestinal metaplasia at the same site was also higher in the treatment group than in the placebo group (36.6% vs 18.3%, P < 0.001). However, no significant difference in grade was found for either glandular atrophy or intestinal metaplasia at the antrum.

H. pylori treatment did not reduce the incidence of metachronous adenoma. During follow-up, metachronous gastric adenomas developed in 16 patients in the treatment group and in 17 in the placebo group.

Death from any cause was reported in 11 patients in the treatment group and in six in the placebo group (HR: 1.95).

After three months of trial medication, H. pylori had been successfully eradicated in 167 patients: 80.4% of the treatment group and 5.4% of the placebo group.

Of 41 cases of metachronous gastric cancer, 32 (14%) developed in patients with persistent infection and 9 (5.4%) in patients with eradicated infection. The HR for the development of metachronous cancer in patients with eradicated infection was 0.32 (P=0.002). Moreover, the incidence of metachronous gastric cancer was significantly lower in the group with eradicated infection than in the group with persistent infection (9.1 cases vs 27.9 cases per 1,000 person-years, P=0.003).

No serious adverse events were reported, and mild drug-related adverse events were more common in the treatment group than in the placebo group.

“Patients with early gastric cancer who received H. pylori treatment had a lower incidence of metachronous gastric cancer and more improvement from baseline in the grade of gastric glandular atrophy at the corpus than did patients who received placebo,” the authors concluded.

In an editorial accompanying the study, Peter Malfertheiner, MD, from Germany, explained that institutionalized screening programs do not exist for gastric cancer prevention in Western countries; however, screening strategies in East Asia are aimed at the detection of gastric cancer at an early and more curable stage and have led to a significant reduction in mortality from the disease.1

Dr. Malfertheiner believes that the results of this study confirm and strengthen previous findings that metachronous cancer can be prevented by H. pylori eradication after endoscopic resection of early gastric cancer. He suggested that H. pylori eradication may stop persistent inflammation to prevent carcinogenic mechanisms, and recommends that such strategies should be implemented before gastric atrophic changes occur, according to local needs and resources.

To read more about this study, click here


  1. Malfertheiner, P. Helicobacter pylori Treatment for Gastric Cancer Prevention. N Engl J Med. 2018;378(12).
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