Older Age and Persistent H. pylori Infection Raise Odds of New Stomach Tumors After Curative Endoscopic Removal of Early Gastric Cancer

Patients who undergo curative endoscopic submucosal dissection (ESD) for early gastric cancer face a substantial long-term risk of developing new tumors in the remaining stomach, and a large retrospective cohort study from Korea now identifies which clinical factors are most closely tied to that risk. In an analysis of 1,200 patients who achieved curative resection of early gastric cancer and were followed for at least 12 months, 185 patients — 15.4 percent of the cohort — developed metachronous neoplasms during surveillance. These new lesions included 102 cases of metachronous cancer and 83 cases of metachronous adenoma only.

The findings, published in Frontiers in Medicine in the gastroenterology section, point to older age and persistent Helicobacter pylori infection as the two factors independently associated with a higher hazard of metachronous neoplasm after curative ESD. Even after curative resection, metachronous recurrence — the appearance of a second, separate neoplasm in the stomach after the first has been definitively removed — remains an important clinical issue during long-term follow-up. The new study quantified that concern precisely: the estimated cumulative probability of developing a metachronous neoplasm was 7.6 percent at three years after ESD and rose to 12.3 percent at five years, meaning roughly one in eight patients could expect a new gastric lesion within five years of curative resection.

To identify which patients carry the greatest risk, the researchers used a Cox proportional hazards model, with time from ESD to the first metachronous neoplasm — or to censoring for patients who remained free of recurrence — as the primary analysis framework. In the adjusted full-cohort model, each additional year of age was associated with a 3.5 percent increase in the hazard of metachronous neoplasm (hazard ratio 1.035 per year, 95 percent confidence interval 1.015 to 1.055, P < 0.001). Persistent H. pylori infection carried an even starker signal: patients in whom the bacterium was not eradicated had a hazard ratio of 2.391 (95 percent confidence interval 1.398 to 4.088, P = 0.001) compared with those without persistent infection — nearly a two-and-a-half-fold elevation in risk.

Diabetes mellitus showed a borderline association with a hazard ratio of 1.391 (95 percent confidence interval 0.988 to 1.958, P = 0.058), a result that narrowly missed conventional thresholds for statistical significance and should be interpreted with caution. The H. pylori finding stands out because, unlike age, it is a parameter that clinicians can measure and act on during follow-up. The study's data indicate that patients who remained infected after their ESD faced markedly higher hazard of a second neoplasm than those without persistent infection.

While the retrospective design of the study means the association cannot be read as proof that eradication therapy would prevent recurrence, the nearly 2.4-fold hazard difference provides a concrete clinical parameter that surveillance programs and treating physicians can incorporate into risk stratification after curative resection. Beyond the primary analysis, the team conducted secondary exploratory analyses using a different comparator: patients who remained free of recurrence for at least 10 years served as controls. In this framework, age and diabetes mellitus were associated with overall metachronous neoplasm.

When the outcome was broken down by lesion type, age and diabetes mellitus were associated with metachronous cancer specifically, while age and lower serum albumin were associated with metachronous adenoma. The divergence between the two analytical approaches is itself informative: the full-cohort model, which adjusts for competing factors across the entire follow-up period, isolated persistent H. pylori infection as a key independent factor, whereas the exploratory comparison highlighted metabolic and nutritional variables. The authors characterize the secondary analyses as exploratory, and the differing patterns underscore that the full-cohort findings on age and H. pylori are the more robust results of the study.

The practical implication of the work is a reinforcement of current surveillance practice rather than a call to change it. Because the cumulative risk of a new neoplasm climbs steadily — from 7.6 percent at three years to 12.3 percent at five years — and because older patients and those with persistent H. pylori infection face disproportionately higher hazards, the findings support continued endoscopic surveillance after curative ESD rather than early discharge from follow-up. For patients treated with ESD, the study offers quantified evidence that a stomach cleared of one cancer is not a stomach freed from cancer risk.

The study's design also defines its limits. The authors note that all claims expressed in the article are solely those of the authors and do not necessarily represent those of their affiliated organizations or the publisher. Nevertheless, with 1,200 patients and a long-term recurrence-free subgroup followed for at least a decade, the analysis provides a detailed statistical portrait of who develops second gastric neoplasms after curative endoscopic resection — and it does so with hazard ratios precise enough to matter for both surveillance scheduling and patient counseling.

Subject of Research: Clinical risk factors for metachronous gastric neoplasms after curative endoscopic submucosal dissection of early gastric cancer

Article Title: Clinical parameters associated with metachronous recurrence after curative endoscopic submucosal dissection for early gastric cancer

Article References: Joo, M. K., Kim, S. H., Kim, W. S., & Lee, B. J. (2026). Clinical parameters associated with metachronous recurrence after curative endoscopic submucosal dissection for early gastric cancer. Frontiers in Medicine, 13, Article 1965395. https://doi.org/10.3389/fmed.2026.1965395

Image Credits: AI Generated

DOI: 10.3389/fmed.2026.1965395

Keywords: early gastric cancer, endoscopic submucosal dissection, metachronous recurrence, Helicobacter pylori, gastric adenoma, surveillance, Cox proportional hazards model, diabetes mellitus, serum albumin, retrospective cohort study, Clinical, parameters