Helicobacter Pylori Treatment for the Prevention of Metachronous Gastric Cancer
May 28, 2018
Summarized by / Author: Rohini Manaktala MD (1), Rooma Nankani MD (1)
Summary Reviewer:Paul Robert Anthony Jr. MD (2)
Contribution To Literature:
This trial revealed the beneficial outcome of treating early gastric cancer with H.pylori eradication therapy and the reduction in future development of metachronous gastric cancer compared to placebo.
The goal of the trial was to determine the incidence of metachronous gastric cancer detected on endoscopy performed at 1-year follow up or later and improvement from baseline in the grade of glandular atrophy in the gastric corpus lesser curvature at the 3 year follow up for individuals with early gastric cancer status post resection and treatment with H.pylori eradication therapy.
It was a prospective, single-center, double-blinded, placebo-controlled and randomized trial performed at the National Cancer Center in South Korea that enrolled patients from August 2003 through March 2013.
Patients were randomized in a 1:1 fashion before endoscopic resection to either H.pylori eradication therapy (n = 236) or placebo (n = 234). The treatment group received amoxicillin 1000 mg, clarithromycin 500 mg and proton-pump inhibitor rabeprazole 10 mg which were given twice daily for a week. The placebo group received rabeprazole 10 mg and placebo pills. Both groups received proton-pump inhibitor for additional 4 weeks to promote ulcer healing.
Total number of patients: 470
Duration of follow-up (endoscopy evaluation): at 3 months, 6 months, 1 year and then every 6 months or 12 months until the last enrolled patient reached the 3 year follow up point
Mean patient age: 59 years
Percentage male: 75%
Between the ages of 18 and 75 years
Histologically confirmed diagnosis of differentiated early gastric cancer or high grade adenoma
Endoscopic localization of a mucosal tumor without ulceration and no lymph-node or distant organ metastasis on CT scan
The stratification factor for group assignment was the severity of the baseline grade of histologic atrophy at the antrum
Paients started the assigned trial medication within 1 week after endoscopic resection
Quadruple antibiotic therapy (proton-pump inhibitor, bismuth, metronidazole, tetracycline) was provided for 10 days if H.pylori infection was detected at closeout endoscopic examination
The development of metachronous gastric cancer was found to have occurred in 7.2% of the treatment group and in 13.4% of the placebo group (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.26-0.94; P=0.03).
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 for such improvement was 5.30 (95% CI, 3.08 to 9.13) in the treatment group as compared with the placebo group.
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.
Major adverse events included death from any cause which was reported in 11 patients in the treatment group and in 6 in the placebo group (HR, 1.95; 95% CI, 0.72-5.27; P=0.19).
Minor adverse events included: taste alteration, nausea, vomiting, diarrhea, abdominal pain, hypersensitivity, dizziness, headache and insomnia. These events were more common in the treatment group than placebo (42.0% vs. 10.2%, P<0.001).
The trial demonstrated a significant reduction in metachronous gastric cancer development among patients who had received treatment for H.pylori infection than those who had received placebo. This is because persistent inflammation of gastric mucosa from H.pylori infection promotes carcinogenesis and increases tumor growth/invasion. Findings from this trial are in agreement with results from previous systemic reviews and open label trials. Additionally, this trial found that the proportion of patients with improvement in the grade of gastric corpus atrophy from baseline was significantly higher in the treatment group than placebo at the 3 year follow up.
An advantage of this trial was a longer duration of follow up than previous trials (median follow up 5.9 years versus <3 years). However there are some limitations to the trial which include: (i) disappearance of preventive effect of H.pylori treatment on metachronous cancer after follow up duration of more than 5 years and (ii) exclusion of patients with synchronous gastric cancers that were initially missed but detected within 1 year after treatment. Moreover, in this trial hazard ratio for incidence of metachronous gastric cancer was found to be higher than previous trials which could be explained by the fact that H.pylori eradication was not confirmed and salvage treatment was not given to patients who failed eradication therapy due to the limitation of blinded process.
In conclusion, H.pylori therapy reduces but cannot completely eradicate the risk of metachronous gastric cancer. Also, it was found that H.pylori treatment did not affect the subsequent incidence of gastric adenoma or overall survival.
Choi I., Kook M., Kim Y., et al. Helicobacter Pylori Therapy for the Prevention of Metachronous Gastric Cancer. NEJM. 2018, 378 (12): 1085-1095. Source
1. Department of Internal Medicine, University of Connecticut Health Center
2. Department of Infectious Disease, Saint Francis Hospital, Hartford, Connecticut