H Pylori eradication decreases metachronous gastric cancer

A recent South Korean study found that H Pylori treatment in those with early gastric cancer led to a 50% decrease in subsequent gastric cancers (see hpylori rx dec metachronous gastric ca nejm2018​ in dropbox, or DOI: 10.1056/NEJMoa1708423)

Details:

--396 patients who had early gastric cancers or high-grade adenomas and were H Pylori positive, from 2003-2013

--mean age 60, 73% male, 60% alcohol drinker, 40% smoker, tumor size 1.7 cm, 82% in lower part of stomach, 66% well-differentiated tubular adenocarcinoma/26% moderately-differentiated/7% high-grade adenoma, 90% in the mucosa/10% submucosa, 70% marked atrophy at lesser curvature

--randomized to H Pylori eradication vs placebo: meds used were amox 1 gm, clarithro 500mg and rabeprazole 10mg bid for 7 days vs just rabeprazole (a PPI) 10mg plus placebo in the control group

--3 months after treatment, H Pylori was successfully eradicated in 80% in the treatment group and 5% in placebo

--endoscopy was done at 3 months post-resection, 6 months, 1 yr, then every 6-12 months until last enrolled patient reached 3-yr followup

--primary outcomes: incidence of metachronous (subsequent) gastric cancer after >1 year; improvement from baseline in grade of glandular atrophy at 3-year follow-up. H pylori was assessed by rapid urease test and Wright-Giemsa staining on biopsies

--median followup of 5.9 years

Results:

--metachronous gastric cancer developed in 14 patients (7.2%) in the treatment group and in 27 patients (13.4%) in the placebo group (hazard ratio in the treatment group, 0.50; 95% confidence interval, 0.26 to 0.94; P=0.03)

--327 patients in the subgroup that underwent histologic analysis: improvement from baseline in the atrophy grade at the gastric corpus lesser curvature was observed in 48.4% of the patients in the treatment group and in 15.0% of those in the placebo group (P<0.001). OR for improvement was 5.30 (3.08-9.13)

--in those who had successful H Pylori eradication: 9 cases of gastric cancer (5.4%) vs 41 with persistent infection (14.0%), hazard ratio of 0.32 (0.15-0.66), p=0-002

--benefit was evident after 3-4 years and increased over time
--metachronous adenomas were not reduced by H pylori treatment, and neither was survival

--There were no serious adverse events; mild adverse events related to the meds were more common in the treatment group (42.0% vs. 10.2%, P<0.001)​

Commentary:

--H Pylori has been considered a class 1 carcinogen for gastric cancer by the WHO since 1994

--South Korea has had a screening program for gastric cancer (the most prevalent cancer in the country) since 1999, finding that endoscopy screening has led to a 47% decreased gastric cancer mortality, with a graded response: those with 1 screen had a 40% decrease, 2 screens 68% and 3 screens 81% decrease. there was an overall 67% prevalence of H pylori in 1998 in South Korea, decreasing to 54% in 2012, though H pylori was not a specific target of the screening 

--the therapy for early gastric cancer has been endoscopic resection, which preserves the stomach, but can result in subsequent (metachronous) gastric cancer at 3% per year

--this trial did not confirm H pylori eradication as an explicit part of the study, which might have limited its results since 20+% of South Koreans have clarithromycin resistance. But, as noted, the post-hoc analysis of those who did have effective elimination of H pylori showed even greater benefit (68% lower risk) than the overall group (50%)

--though the effect of elimination of H Pylori in several studies is somewhat conflicting, a few prior blogs looked at this issue:

    --a systematic review/meta-analysis found a 46% lower incidence of gastric cancer with H Pylori eradication, see http://gmodestmedblogs.blogspot.com/2019/04/h-pylori-eradication-and-reduced-risk.html 

    --a study on H pylori treatment but continued use of PPIs led to an increase in gastric cancer, but the blog also goes into the different H Pylori strains along with epidemiologic data on gastric cancer prevalence, and reference to several other blogs on H Pylori and its treatment, see http://gmodestmedblogs.blogspot.com/2018/01/h-pylori-ppi-use-and-gastric-cancer.html 

as  mentioned in other blogs, there is some argument in the literature that H Pylori infection may protect against asthma/allergies, or that it might decrease esophageal cancer, even that it is so common that it actually functions as a normal intestinal commensal microbe that has evolved with its human host. i would argue that:

--the data are pretty consistent regarding its association with gastric cancer

--the decrease  of esophageal cancer esp with the CagA variant may be real (since the pH of the stomach and acid reflux into the esophagus is less), though the incidence of esophageal cancer worldwide does pale in comparison to that of stomach cancer

--the association found with asthma/allergies is somewhat tenuous as we have learned more about the microbiome, eg living in more industrialized vs more traditional societies and the "hygiene hypothesis". see http://gmodestmedblogs.blogspot.com/2016/08/microbiome-and-type-1-diabetes-etc.html ​ , and http://gmodestmedblogs.blogspot.com/2015/10/gi-microbiome-in-little-kids-and.html 

so, this article does add to the argument that we should test and treat those with H pylori infections. As mentioned in one of the blogs above, there are different CagA variants of H pylori with apparently different outcomes. so, perhaps an appropriate approach might be to aggressively test and treat those with ongoing H pylori infections (not just positive H pylori antibodies) who come from countries with a high incidence of gastric cancer.