gastric cancer screening/prevention; h pylori

I have had 2 Cape Verdean patients over the past few years who have developed gastric cancer.  Several months ago I met with a Cape Verdean doctor who confirmed that gastric cancer was relatively common in Cape Verde.  Gastric cancer screening in general does not make sense in the United States given the low prevalence of gastric cancer.  However, many of our patients come from countries with much higher prevalence, prompting this review.  I am sending this out  generally because many of us see patients coming from high prevalence countries.

 

Most of the data is not great.  There has been mass population screening in Japan since 1983  for individuals over 40, where gastric cancer is the leading cause of cancer death.  A systematic review was done by the Japanese Health Ministry (see gastric ca screening japan 2008 in dropbox, or doi:10.1093/jjco/hyn017), which only found 10 studies directly related to screening, none of which were randomized controlled trials -- only case-control or cohort studies.  They noted in Japan there has been an overall decrease of gastric cancer mortality from 1980 to 2003, from 69.9 to 34.5 per 100,000 in males, and 34.1 down to 13.2 per 100,000 in females.  In their systematic review they found that the best evidence was for barium studies (the most widely used intervention), finding a 40-60% decrease in gastric cancer mortality and a 5 year survival rate of 74-80% for those screened versus 46-56% for the non-screened group.  They found that the data were more mixed and less compelling for endoscopy screening, or blood tests for serum pepsinogen or Helicobacter pylori antibody.  A cohort study in Korea, looking retrospectively at 2485 patients with gastric adenocarcinoma, found that those screened at 4-5 year intervals had a higher risk for gastric cancer than those screened at 2-3 year intervals. Those at the highest risk, people with a family history of gastric cancer and those in their 60s, were found to have a higher stage of gastric cancer when the intervention was performed every 3 years as opposed to annually.  This all led to the recommendation for screening every 2 years by upper GI series or endoscopy for individuals over 40 years old.  Since none of these studies were RCTs, there may be significant biases (lead time bias, length bias, etc.)

 

There was an RCT in 2004 on H. pylori eradication as a means to prevent gastric cancer ( see hpylori and gastric cancer jama 2004 in dropbox, or JAMA 2004; 291: 187-194).  In this Chinese trial (from Fujian Province, where mortality rate from gastric cancer is 153/100K, and where they have found a 2-4 fold increase in gastric cancer in those H pylori positive) 1630 healthy carriers of H. pylori were enrolled, of whom 988 did not have any precancerous lesions on endoscopy (gastric atrophy, intestinal metaplasia, or gastric dysplasia) at study entry.  The H. pylori status was documented by the endoscopic exam.  Patients were randomly assigned H pylori therapy (a two-week course of omeprazole 20 mg, amoxicillin/clavulanate 750 mg, and metronidazole 400 mg, all twice a day) versus placebo, and followed 7.5  years.  Results:

 

        --76.4% of patients given triple therapy for H pylori were  successfully treated, per urea breath test.  Those who failed treatment were given quad therapy --the ultimate eradication rate was 83.7%

      --Primary outcome (incidence of gastric cancer during followup): No difference, with 7 cases in the H. pylori treatment group and 11 cases in the placebo.

        --Secondary outcome (incidence of gastric cancer, comparing those with or without precancerous lesions): In those without precancerous lesions none developed gastric cancer in those treated for H. pylori, 6 did the placebo group, statistically significant.  Of note, the cumulative incidence of cancer in the placebo group was increasing dramatically after about 6 years, whereas those were H. pylori negative remained without cancer (ie very impressive splaying of the curves).

        --Smoking and older age were independent risk factors for the development of gastric cancer, with smoking, having a hazards, ratio of 6.2.

 

so, what is one to do in the United States?  At this point, given the lack of large RCTs, it seems to me to be hard to recommend an aggressive screening program with either upper GI radiography or endoscopy.  However, given the very high prevalence of H pylori infection in many of these patients (including our Cape Verdean patients), and given the known association of H. pylori infection and gastric cancer at least in some high prevalence countries, and given the RCT from Fujian Province,  I personally think that it would be appropriate to screen and treat patients for H pylori infection, using the H. pylori antibody as a reasonable marker of infection.