H Pylori treatment in elderly dec gastric cancer

​A recent analysis of a Hong Kong database found that older individuals receiving clarithromycin-based H. pylori eradication had a lower risk of gastric cancer (see h pylori treatment dec gastric ca older pts gastro2016 in dropbox, or 

doi: https://doi.org/10.1053/j.gastro.2018.03.028)

Details:

-- 73,237 subjects were identified in the Hospital Authority database of Hong Kong who had H. pylori infections and received a course of triple therapy for H. pylori eradication that contained clarithromycin.

-- H. pylori testing is not routinely performed in Hong Kong unless there are dyspeptic symptoms or upper endoscopy is performed for other reasons.

-- mean age 55 at the time of H. pylori treatment, 47% male, history of peptic ulcer in 5%, upper endoscopy diagnosed H. pylori in 83%, diabetes 13%/hypertension 22%/dyslipidemia 9%/ischemic heart disease 10%

-- 13.4% needed retreatment for H. pylori, defined as having a subsequent prescription of another course of eradication therapies including either repeat triple therapy, a second line (bismuth-containing quadruple therapy or PPI/levofloxacin/amoxicillin therapy) or third line therapy (rifabutin-containing), determined by record review

Results:

-- among those receiving H. pylori eradication therapy, 0.27% (3.2 per 10,000 person-years) developed gastric cancer during a median follow-up time of 7.6 years; among those who were retreated the incidence rate was 0.48% (6.2 per 10,000 person-years)

-- compared with the matched general population, 18% lower​ gastric cancer risk in those >60 years old receiving treatment, standardized incidence ratio 0.82 (0.69-0.97), p=0.02

-- the risk of gastric cancer was significantly higher in male versus female subjects who received H. pylori treatment who were >60 years old (RR 1.8, p=0.001); as well as in those 40 to 59 years old who required retreatment for the infection (RR 2.5, p=0.003)

-- on reviewing their graphs comparing expected versus observed cases of gastric cancer by age group:

    -- no difference before 10 years after therapy in any age group

    -- a trend but no significant difference in those <40 years old

    -- a significant 68% decrease in those in the 40-59 age group (0.08 - 0.88), p=0.04 (mean annual incidence rate of 3 vs 9.2 cases in 27,439 people)

    -- a significant 58% decrease in those >60 years old (0.18-0.84), p=0.02 [though the absolute risk reduction was much higher in this group, given the much higher prevalence of gastric cancer: mean annual incidence rate of 7 vs 16.1 cases in 8747 people)

Commentary:

-- H. pylori infection is the most frequent bacterial infection the world, infecting more than 50% of individuals in less developed regions. This infection has been identified as the major etiologic factor for gastric cancer. [i have also found H Pylori infection in several US-born people who have never traveled to less-developed countries, so testing should still be considered in clinical situations which might implicate H Pylori: eg dyspepsia, and even a case where someone had refractory ITP]

-- Gastric cancer is typically diagnosed in older patients; in Hong Kong the mean age of diagnosis in men is 71 and women 68 years of age

-- A prior blog evaluated a systematic review/meta-analysis finding that those with H. pylori infections who were treated seem to have a 46% lower incidence of gastric cancer, with more impressive reductions in high prevalence H. pylori  regions (see http://gmodestmedblogs.blogspot.com/2019/04/h-pylori-eradication-and-reduced-risk.html/ ).

-- A few studies have looked at treating patients with preneoplastic or neoplastic lesions, with somewhat mixed results. For example a Chinese study found progression of preneoplastic gastric lesions to gastric cancer even with H. pylori eradication. Another study found that after endoscopic resection of early gastric cancer, there seemed to be a decrease in the development of metachronous cancers.

--The current analysis suggests that gastric cancer protection by treating H. pylori infections extends to older individuals. The fact that younger people did not show as much protection probably reflects the fact that gastric cancer is much more common in older patients, and this study only had a 13 year follow-up (i.e., the incidence of developing gastric cancer, even in those H. pylori positive, does not become evident for at least 10 years, so younger people did not reach an age where gastric cancer is sufficiently common).

--And, though treatment in the older patients is helpful, earlier treatment is likely more beneficial overall, since treatment takes the 10 years to show benefit, several of these older patients probably had pre-existing neoplastic gastric lesions where the benefits of therapy are not as clear, and earlier treatment does not seem to be associated with later reinfection by H pylori (per other studies). So treating younger patients should have a more longterm benefit than identifying at treating those >60 years old, though would be good to have a study with longer follow-up to be sure.

-- There are a few limitations to the study, a large database analysis of the population:

    -- there was no cohort of untreated H. pylori subjects as a comparison group, since the general practice in Hong Kong was to treat all cases found [and their cases were symptomatic, so cannot comment on the effects of treating asymptomatic people from this study]

    -- therefore, comparisons to the general untreated population likely includes a large number of infected as well as uninfected patients (the local prevalence of H. pylori being 56%), so the likelihood of gastric cancer benefit is  probably considerably more than the above numbers reflect.

    -- They only included patients treated with clarithromycin-based therapies, though this was the majority treatments prescribed at that time in Hong Kong

    -- this study only included patients in the Hospital Authority database, though this system provides about 90% of local Healthcare Services.

    -- The local practice was to check for H. pylori eradication, though these data were not available in the database.

-- About 13.4% of the patients needed H. pylori retreatment, pretty much the expected rate, but this was determined by scouring the database and finding that another therapy was subsequently given. We do not have data on the successful eradication rates in these patients (who had twice the risk of gastric cancer as those treated only once), but it likely was lower than those treated with one course of therapy (perhaps these patients had harder-to-treat variants of H pylori, this group included more individuals who were nonadherent to therapy, …)

So, this study further supports aggressive detection and treatment of H. pylori, even in those older than 60. It should be noted, as above, that there is an approximately 10 year lag after therapy to  observe a decrease in gastric cancer, and that the incidence of gastric cancer increases exponentially with age, so that likely optimization of results would be through earlier detection and treatment. And it probably makes sense to confirm H. pylori eradication after therapy.​