A large pragmatic randomized clinical trial in Taiwan found that adding Helicobacter pylori screening to an existing colorectal cancer screening program did not significantly reduce gastric cancer incidence or mortality rates over approximately 5 years of follow-up.

In the study, published in JAMA, researchers randomized 240,000 residents aged 50 to 69 years to receive an invitation for either H. pylori stool antigen (HPSA) testing plus fecal immunochemical testing (FIT) or FIT alone.

The trial was conducted between January 1, 2014, and September 27, 2018, with final follow-up on December 31, 2020. Among the 240,000 randomized adults (mean age = 58.1 years, standard deviation = 5.6; 46.8% female), 63,508 of them were invited for HPSA  plus FIT, and 88,995 were invited for FIT alone. Screening participation rates were 49.6% (n = 31,497/63,508) for HPSA plus FIT and 35.7% (n = 31,777/88,995) for FIT alone.

Among those invited, gastric cancer incidence rates were 0.032% in the HPSA plus FIT group and 0.037% in the FIT-alone group (mean difference = −0.005%, 95% confidence interval [CI] = −0.013% to 0.003%, P = .23). Gastric cancer mortality rates were 0.015% in the HPSA plus FIT group and 0.013% in the FIT-alone group (mean difference = 0.002%, 95% CI = −0.004% to 0.007%, P = .57).

Among the 12,142 participants (38.5%) with positive HPSA results, 8,664 (71.4%) received antibiotic treatment, and eradication occurred in 91.9%. The most common adverse effects among the participants who received antibiotics were abdominal pain or diarrhea (2.1%) and dyspepsia or poor appetite (0.8%).

The study design integrated H. pylori screening with an existing FIT-based colorectal cancer screening program. Participants in the HPSA plus FIT group who tested positive for H. pylori were referred for standardized 10-day sequential antibiotic therapy: for days 1 through 5, esomeprazole (40 mg) once daily and amoxicillin (1 g) twice daily; for days 6 through 10, esomeprazole (40 mg) once daily and clarithromycin (500 mg) plus metronidazole (500 mg) twice daily. Posttreatment H. pylori status was assessed using HPSA at 6 to 8 weeks following treatment completion.

Among the participants who underwent screening, rates of gastric cancer were 0.028% in the HPSA plus FIT group and 0.040% in the FIT-alone group (mean difference = −0.013%, 95% CI = −0.026% to 0.0001%, P = .05). Gastric cancer mortality rates were 0.010% in the HPSA plus FIT group and 0.016% in the FIT-alone group (mean difference = −0.006%, 95% CI = −0.014% to 0.002%, P = .13).

The study also reported outcomes related to colorectal cancer. Among all invited participants, colorectal cancer incidence rates were 0.122% in the HPSA plus FIT group and 0.141% in the FIT-alone group (mean difference = −0.019%, 95% CI = −0.035% to −0.003%, P = .02). Colorectal cancer mortality rates were 0.021% in the HPSA plus FIT group and 0.030% in the FIT-alone group (mean difference = −0.009%, 95% CI = −0.016% to −0.002%, P = .02).

Among the participants who underwent screening, rates of colorectal cancer were 0.104% in the HPSA plus FIT group and 0.119% in the FIT-alone group (mean difference = −0.015%, 95% CI = −0.038% to 0.008%, P = .21). Colorectal cancer mortality rates were 0.010% in both groups (difference = 0%, 95% CI = −0.007% to 0.007%, P > .99).

The percentages of advanced-stage gastric and colon cancers (stage II to IV) at the time of diagnosis were similar between the two groups. For gastric cancer, 75.3% of cases in the HPSA plus FIT group and 75.5% in the FIT-alone group were advanced stage. For colorectal cancer, 59.4% in the HPSA plus FIT group and 58.7% in the FIT-alone group were advanced stage.

The H. pylori reinfection rate was 0.3% (95% CI = 0.1%–1.6%), based on the follow-up of patients who had received successful treatment for a minimum of 2 years.

Among the 5,858 participants who underwent upper endoscopy following positive H. pylori tests, 1,843 (31.5%) of them had peptic ulcers.

The researchers noted several limitations of the study, including the relatively short follow-up period, differences in baseline characteristics between groups, and potential lack of generalizability to communities with different H. pylori prevalence rates. Additionally, among the 240,000 individuals randomized, 38,792 were unreachable for an invitation, which may have affected the validity of the results.

The authors declared having no competing interests.