Gastric Cancer after <italic>Helicobacter pylori</italic> Eradication: Characteristics, Diagnosis, and Management.

Introduction
Gastric cancer remains the fifth most common cancer, was responsible for over one million new cases in 2020, and is the fourth leading cause of cancer deaths globally [1]. Helicobacter pylori infection has been classified as group 1 carcinogen and is considered the principal cause of non-cardia gastric cancer [2]. It is estimated that more than 85% of non-cardia gastric cancers could be prevented if the population were not infected with H. pylori [3]. The incidence and mortality rates of non-cardia gastric cancer have steadily declined over the past half-century, largely due to global efforts for eradication and reduced prevalence of H. pylori [4, 5].
However, gastric cancer still develops after successful H. pylori eradication [6, 7]. Although eradication significantly reduces gastric cancer risk, it does not completely prevent carcinogenesis partly because of the heterogeneous nature of gastric cancer etiology and partly because of irreversible histologic, genetic, and epigenetic alterations in gastric mucosa. Persistent precancerous lesions, such as atrophic gastritis (AG) and intestinal metaplasia (IM), sustain a risk of malignant transformation within gastric mucosa, even after H. pylori eradication [8–12]. Notably, AG and IM should be understood as high-risk background mucosa, not obligate precursors, creating a field effect in which malignant transformation arises from gastric stem cells [13]. Epigenetic modifications, particularly DNA methylation, persist beyond eradication [14, 15], although some are reversible [16–24]. Gastric cancer after H. pylori eradication presents distinct clinical, histological, and molecular features compared with gastric cancer developing without eradication, highlighting the importance of understanding the underlying mechanisms to optimize surveillance and treatment strategies.

Carcinogenesis of Gastric Cancer after H. pylori Eradication

H. pylori infection is a major risk factor for gastric cancer and a central component of Correa’s cascade, in which chronic gastritis progresses through atrophy, IM, and dysplasia to intestinal-type cancer [25–27]. Over 85% of non-cardia gastric cancers are attributable to H. pylori infection [3]. H. pylori eradication is recognized as an effective preventive strategy. However, H. pylori eradication does not fully eliminate the risk of gastric cancer. Eradication reduced the risk of gastric cancer by 63% among individuals without precancerous lesions and by 43% overall, regardless of histological findings in a 27-year follow-up study [28]. A meta-analysis of randomized clinical trials (RCTs) reported 46% and 39% reductions in incidence and mortality, respectively [29].
Residual cancer risk may stem from causes independent of H. pylori. Approximately 3–5% of gastric cancers develop independently of H. pylori infection due to other causes, such as Epstein-Barr virus infection, genetic abnormalities in the host, autoimmune gastritis, or proximal cancers related to acid reflux [30]. More importantly, irreversible mucosal changes, including advanced atrophy, IM, and genetic alterations present at eradication, continue to drive carcinogenesis despite bacterial clearance.

Incomplete Recovery of Gastric Mucosa after H. pylori Eradication
The extent to which precancerous lesions such as AG and IM regress after H. pylori eradication may influence the potential to reduce gastric cancer risk. Many studies have consistently noted that inflammation and mucosal activity decrease after H. pylori eradication, indicating partial recovery of gastric mucosal change [9, 31, 32]. Yet, whether precancerous lesions can reverse after eradication remains uncertain.
Eradication prevents further mucosal damage, yet cancer risk reduction is most effective if treatment occurs before advanced atrophy. Thus, residual risk depends on the extent and severity of AG at eradication [30]. Previous studies have reported improvements in AG after H. pylori eradication, but the findings for IM remain inconsistent [33–35]. A series of investigations with 5- to 10-year follow-up has observed improvement in AG in the antrum and corpus, as well as regression of IM in the lesser curvature of the corpus [8, 9]. However, a meta-analysis reported significant regression of AG in the antrum and corpus, whereas IM exhibited no significant changes [10]. Another meta-analysis by Wang et al. [11] observed improvement in corpus atrophy but found limited benefit for atrophy in the antrum or for IM in the corpus and antrum. Overall, AG is generally considered a reversible lesion, whereas advanced IM is regarded as an irreversible change once established. The multistep progression of gastric carcinogenesis and the partial reversibility of precancerous lesions after H. pylori eradication are illustrated in Figure 1.

Genetic/Epigenetic Alteration Involved in Gastric Cancer after H. pylori Eradication
Exposure to carcinogenic factors leads to the accumulation of genetic and epigenetic alterations throughout the multistep process of carcinogenesis [36]. Gastric cancer risk reflects the interaction of H. pylori virulence, host genetics, and environmental factors [37, 38]. H. pylori infection triggers inflammation that accelerates cellular turnover in the gastric mucosa and generates a microenvironment rich in reactive oxygen and nitrogen species, thereby increasing DNA damage and mutation [39–41]. Beyond inflammation, H. pylori infection induces genetic and epigenetic alterations within gastric epithelial cells that contribute to genomic instability, while advancing tumors acquire the capacity to avoid immune surveillance and invade surrounding tissues [42, 43]. Studies on whether such alterations are reversible remain limited. Some epigenetic alterations have been shown to be reversible following eradication. Thus, the successful elimination of chronic H. pylori infection could serve as a preventive strategy to suppress the accumulation of molecular abnormalities and mitigate the precancerous gastric environment.

Genetic Alteration Involved in Gastric Cancer after H. pylori Eradication
Gastric carcinogenesis involves genetic and epigenetic changes induced by various carcinogenic factors [44]. In gastric cancer, driver mutations remain relatively rare except TP53 and CDH1. Although driver genes like ARID1A and RHOA have been identified, alterations in these genes account for only a minority of cases [44, 45]. H. pylori infection contributes to DNA repair defects, oncogene activation, inactivation of tumor suppressor genes, and telomerase activation. Although H. pylori eradication has not been shown to reverse chromosomal abnormalities such as the loss of heterozygosity or microsatellite instability (MSI) within the gastric mucosa [46], the extent to which genetic alterations may be restored following eradication remains unclear.

Mismatch Repair Deficiency. MSI, resulting from mismatch repair (MMR) deficiency, leads to replication errors in simple repetitive sequences known as microsatellites [47]. MSI has been observed not only in gastric cancer but also in precancerous lesion such as IM, suggesting that MSI may play a role in early stage of gastric cancer development [48, 49]. MSI is closely linked to these gastric mucosal alterations induced by H. pylori infection [50–52]. Although eradication raises the possibility of reversing some MSI as H. pylori infection is associated with decreased expression of MMR proteins, including hMLH1 and hMSH2, frameshift mutations in hMSH3 and hMSH6 and the loss of hMLH1 and hMSH2 function may contribute to persistent genomic instability that can persist despite H. pylori eradication. However, recent evidence suggests that some MMR protein expression may partially recover after eradication therapy [52, 53], indicating that the process may not be entirely irreversible in all cases.

Oncogenes and Tumor Suppressor Genes. Several oncogenes involved in promoting cell proliferation, inhibiting apoptosis, and inducing phenotypic changes, including c-met, HER2 (c-erbB2), c-erbB3, K-sam, ras, and c-myc, are subject to mutation, amplifications, or overexpression during gastric carcinogenesis [54, 55]. Conversely, tumor suppressor genes such as p53, p16, APC, and RUNX3 become inactivated [54, 56–58]. However, there is currently limited evidence that eradication of H. pylori can reverse such genetic alterations once established.

Telomere and Telomerase. Shortening of telomeres and activation of telomerase have been reported in intestinal metaplasia, suggesting their involvement in the pathogenesis of intestinal-type gastric cancer [59, 60]. Studies have indicated that H. pylori infection may reactivate telomerase [61, 62], and telomerase activity has been observed to decrease following H. pylori eradication [61]. Further investigations are needed to clarify the clinical implications of changes in activity of telomerase in gastric cancer development.

Epigenetic Alteration
While H. pylori eradication has limited efficacy in suppressing oncogene activity or reversing the silencing of tumor suppressor genes, epigenetic silencing may be reversible. In gastric cancer, tumor suppressor or tumor-related genes are more frequently inactivated by CpG island hypermethylation than by mutations [63]. Integrated analyses of genetic and epigenetic alterations indicate that inactivation of tumor suppressor genes such as p16, hMLH1, and CDH1 occurs more commonly through aberrant DNA methylation than through mutations [64]. Several studies have shown that successful eradication of H. pylori can reduce DNA methylation and restore the histological phenotype in non-neoplastic mucosa, though this effect appears limited to mucosa not yet beyond the “point of no return.”

Gene Promoter Methylation. Aberrant DNA methylation is a key mechanism of epigenetic gene silencing, and dysregulation of this process is widely recognized as a crucial contributor to various human cancers [65]. Gene promoter methylation is a primary form of epigenetic alteration responsible for suppressing gene expression [15]. Chronic inflammation triggered by H. pylori infection leads to the accumulation of aberrant DNA methylation in gastric mucosal cells [66, 67]. This process contributes to the silencing of multiple tumor suppressor genes [64] and the activation of retrotransposons [68, 69]. Promoter hypermethylation of genes including p16, CDH1, MGMT, MLH1, APC, and RUNX3 has been reported in gastric cancer [70]. H. pylori infection has been shown to induce promoter hypermethylation of genes like p16, CDH1, and MLH1 [63]. Studies examining the effects of eradication on epigenetic alterations revealed gene-specific changes through promoter methylation in CDH1, APC, COX2, MLH1, and p16 in gastric mucosa [20].
Eradication has been observed to reduce methylation levels, though the degree of reduction varies depending on specific genetic markers and persists over the long term [21, 24]. Persistent methylation levels after eradication may reflect methylation within gastric stem cells, representing a permanent epigenetic component. In contrast, methylation in differentiated cells may decline over time as these cells are replaced by newly generated, unmethylated cells, constituting a transient component [71]. RCTs in Hong Kong demonstrated that eradication therapy reduced E-cadherin (CDH1) promoter methylation density and subsequent neoplastic transformation [18, 19], and Sepulveda et al. [22] reported a significant decrease in CpG island hypermethylation of the MGMT gene within 6–8 weeks after eradication from 70% to 48%.
A long-term follow-up study demonstrated that H. pylori eradication reduced gene methylation in non-intestinal metaplasia (non-IM) mucosa but not in IM. CpG island methylator phenotype (CIMP) was more frequently observed in the IM of patients who developed gastric cancer after eradication [53]. Nakajima et al. [21] reported that methylation levels gradually declined with reduced inflammatory infiltration after eradication; however, in patients who had undergone endoscopic resection (ER), levels remained significantly higher than in healthy controls.

miRNA. miRNAs are non-coding RNAs, approximately 18–25 nucleotides in length, that play a role in post-transcriptional gene silencing [72, 73]. H. pylori infection alters the expression profiles of various miRNAs, contributing to increased genetic instability [39, 43]. Silencing of miRNA genes through DNA methylation has been suggested as an additional mechanism contributing to the epigenetic field defect in gastric cancer. Methylation levels of miR-124a-1, miR-124a-2, and miR-124a-3 were significantly elevated in H. pylori-infected individuals and remained high even after eradication [74].
The relationship between miRNA expression changes after eradication and the risk of gastric cancer remains unclear. Among 30 miRNAs that were downregulated in H. pylori infection, 14 showed recovery after eradication [75]. A case-control study matching patients who had undergone ER for early gastric cancer with healthy controls by sex and age found dysregulation of specific miRNAs in the gastric mucosa exhibiting corpus gastritis induced by H. pylori. While eradication led to improvement of miRNA expression profiles in non-metaplastic mucosa, miRNA alterations persisted in the gastric mucosa of patients with IM or those at high risk for gastric cancer [76]. A comprehensive summary of molecular alterations and clinicopathological risk factors associated with gastric cancer after H. pylori eradication is presented in Table 1.

Diagnosis of Gastric Cancer after H. pylori Eradication

Endoscopic and Histological Characteristics of Gastric Cancer after H. pylori Eradication

Endoscopic Characteristics

H. pylori eradication may alter tumor morphology and affect detectability, as post-eradication gastric cancers often present as depressed, ulcer-type, or gastritis-like appearance. Matsuo et al. [77] demonstrated that they typically exhibited flat-depressed morphology, resembling cancers in H. pylori-negative patients. Depressed-type lesions were more frequent in patients with early gastric cancer after H. pylori eradication than in H. pylori-positive patients [78, 79]. Ito et al. [80] reported tumors after eradication in the short-term exhibited a superficial-elevated type with reduced height of the lesions. Possible mechanisms include decreased serum gastrin and cytokine levels, which may suppress cell growth and cause lesion flattening [81–85].
A gastritis-like appearance is characterized by uniform papillae or tubular pits with a whitish border, regular or faint microvessels, and unclear demarcation, resembling the adjacent noncancerous mucosa under narrow-band imaging (NBI) with magnifying endoscopy [86]. A gastritis-like appearance was present in 44% of lesions in the eradication group compared to 4% in the non-eradication group [86]. A retrospective study by Kamada et al. [87] reported that 90% of cancers after eradication were ulcer-type, all with severe baseline corpus atrophy. Tumor size has been reported as equal to or smaller than that of cancers in non-eradicated patients [78, 79].

Histological Characteristics
After eradication, nearly normal epithelium often covers adenomas and gastric cancers exhibit mildly atypical surface epithelium [88]. This finding has been termed epithelium with low-grade atypia (ELA) [80]. ELA is characterized by its localization on the surface of gastric cancer tissue, the composition of columnar epithelium with spindle or oval nuclei, preservation of nuclear polarity, and clear distinction from the surrounding non-neoplastic mucosa [89]. It was identified in 22 of 27 post-eradication cancers, frequently expressing gastric-type mucin [89]. Deep sequencing showed mutation profiles of ELA similar to cancer tissue, implying potential reversibility [90, 91]. Non-neoplastic epithelium covered 8% of post-eradication cancers but was absent in infected cases [92], and non-neoplastic columnar epithelium appeared in 8 of 33 patients within a month after eradication, explaining less distinct tumor margins [80].
The cellular origin of ELA remains a subject of ongoing scientific debate. While genomic analyses provide evidence supporting the hypothesis that ELA originates from gastric cancer cells [90], subsequent studies demonstrate that ELA may arise from normal gastric epithelium based on mucin phenotype and proliferation marker profiling [93]. This controversy has important clinical implications for diagnostic strategies and risk assessment, as the cellular origin may influence the prognostic significance and management approach for patients presenting with ELA. Further research is needed to definitively resolve this question and establish standardized diagnostic criteria.
Intestinal-type cancers predominate after eradication, with diffuse-type being rare. In 573 patients followed-up for 6.2 years, 95% of cancers were of the intestinal type, a finding supported by other studies [94–97]. Post-eradication cancers also show lower Wnt5a expression and reduced Ki-67 index, suggesting relatively low aggressiveness [77, 78]. Representative endoscopic and histopathological features of gastric cancer developing after H. pylori eradication are shown in Figure 2.

Challenges in Endoscopic Diagnosis
The indistinct tumor margins and presence of ELA complicate endoscopic detection, delaying early detection of gastric cancer and gastric adenoma [89]. After H. pylori eradication, gastric cancers often present as flat or depressed lesions with a gastritis-like appearance. These lesions typically show pale or whitish mucosa, indistinct borders, and regular or faint microvascular patterns, making them difficult to distinguish from the surrounding non-neoplastic mucosa. The reduced mucosal inflammation and gastrin levels after eradication may contribute to lesion flattening and subtle color change. Careful inspection using image-enhanced endoscopy and magnification is therefore useful for early detection (Fig. 3). Submucosal invasion rates are higher in gastric cancers after eradication compared with H. pylori-positive cases [79, 98].
Image-enhanced techniques such as linked color imaging, NBI, and i-scan have shown utility, but large-scale evidence in post-eradication settings remains limited [99–101]. Magnifying NBI could improve diagnostic accuracy by identifying irregular microvascular and microsurface patterns within reddish depressed lesions and guiding targeted biopsy, which significantly increases diagnostic yield [102–106]. In a randomized trial, blue laser imaging-bright detected early gastric cancer more effectively than white-light imaging (WLI) (93.1% vs. 50.0%), identifying all 14 gastric cancers after eradication compared with only 2 of 11 by WLI (p < 0.001) [106]. Similarly, Kitagawa et al. [107] reported lower miss rates with linked color imaging than WLI (30.7% vs. 64.9%, p < 0.001) in eradicated patients. The distinctive endoscopic and histopathological characteristics of post-eradication gastric cancers, compared with those in H. pylori-positive patients, are summarized in Table 2.

Management and Surveillance

Risk Stratification for Gastric Cancer after H. pylori Eradication
Identifying high-risk patients after successful eradication is recommended for surveillance. While many risk factors overlap with those before eradication, some hold particular significance.

Endoscopic and Histological Risk Factors
A systematic review and meta-analysis by Kodama et al. [108] reported that severe atrophy (RR 3.40), severe intestinal metaplasia (RR 5.38), xanthoma (RR 2.75), and map-like redness (RR 2.34) are significantly associated with increased gastric cancer risk after H. pylori eradication. Despite regression of many H. pylori-associated findings, atrophy, IM, and xanthoma often persist for more than 10 years, supporting their use in risk assessment [108, 109].
A cohort study of 573 patients who underwent eradication reported cumulative gastric cancer incidence rates at 10 years of 0.7%, 3.4%, and 16% for patients with none/mild (C0–C2), moderate (C3, O1), and severe (O2, O3) atrophic changes, respectively [97]. Kodama et al. [110] identified severe endoscopic atrophy, Operative Link for Gastritis Assessment (OLGA) staging (stages 0–II/III, IV), histological atrophy and inflammation in the antrum as risk factors for gastric cancer after eradication. Age and histological atrophy were consistent predictors across studies [111, 112].
IM confers substantial risk for gastric cancer after eradication. Biopsy-based evaluation revealed that IM confined to the antrum increased cancer risk 3.6-fold, while IM extending to the corpus raised the risk 3.7-fold [97]. In a case-control study by Kodama et al. [110], IM in the greater curvature of the corpus showed the strongest association (OR 6.26; 95% CI, 1.28–30.60; p = 0.023). Although undifferentiated gastric cancer is relatively rare, it can still develop long after H. pylori eradication, with female sex and the lack of follow-up identified as risk factors, indicating the importance of long-term surveillance [113].
While there is limited data on risk factors specific to primary gastric cancer after eradication, several factors, including endoscopic and histological atrophy, histological IM, male sex, advanced age, and delayed eradication therapy, have been implicated as risk factors for both primary and metachronous gastric cancer. In contrast, BMI, smoking, endoscopic IM, and map-like redness appeared to be specific to metachronous cancer [114]. Further long-term studies are warranted to clarify endoscopic predictors for both cancer types and guide surveillance strategies.

Molecular Biomarkers
Gene expression analyses show that gastric cancers arising after H. pylori eradication possess distinct molecular features, with DNA methylation-related markers drawing particular interest for risk stratification. A genome-wide methylation study identified novel epigenetic markers (FLT3, LINC00643, RPRM, JAM2, ELMO1, BHLHE22, RIMS1, GUSBP5, and ZNF3) that were significantly hypermethylated in gastric cancer tissues compared to atrophic mucosa after eradication [115]. The accumulation of aberrant epigenetic alterations, referred to as epimutation burden, has been shown to strongly correlate with the methylation level of a single marker gene [116].
In a multicenter prospective study, miR124a-3, a DNA methylation marker, could predict the risk of metachronous gastric cancer in patients who had undergone ER. However, its clinical utility was limited, as the cancer incidence remained high even in patients with the lowest methylation levels [117, 118]. The DNA methylation level of RIMS1 in the gastric mucosa could stratify gastric cancer risk among patients with open-type atrophy after eradication. The highest quartile of RIMS1 methylation was associated with markedly increased incidence compared to those in the lowest quartile, with a 25.7% methylation threshold proposed for intensive endoscopic surveillance [119].
Despite promising preliminary results, several significant barriers prevent the clinical implementation of these molecular biomarkers: current detection methods vary widely among laboratories, with no consensus on optimal sample preparation, analysis protocols, or cutoff values. Most studies have been conducted in limited ethnic populations or geographic regions, resulting in insufficient validation across diverse cohorts. The economic impact of biomarker testing compared with standard endoscopic surveillance remains uncertain, as no formal cost-effectiveness analyses have been performed. Moreover, existing evidence is largely derived from retrospective or proof-of-concept investigations, lacking prospective trials that demonstrate improved patient outcomes. Technical variability between laboratories and the need for specialized equipment further restrict widespread implementation. Taken together, these challenges highlight that current biomarker research remains exploratory and that further validation, methodological standardization, and prospective evaluation of clinical benefit are required before routine application can be justified.
Persistence of MSI or Das-1 expression after eradication could indicate a high-risk group for metachronous gastric cancer development [120], and MOS methylation has been linked to recurrence after ER [24, 121]. Eradication therapy may partially reverse DNA methylation and support the reduced incidence of metachronous gastric cancer. CDH1 methylation significantly declined 2–4 years after eradication in patients regardless of family history but remained elevated for more than 5 years in those with prior gastric cancer [122].

Additional Clinical Risk Factors
Serum pepsinogen levels change after H. pylori eradication. Haneda et al. [123] proposed an optimal cutoff of 4.5 for the pepsinogen I/II ratio (PGI/II) for gastric cancer after eradication, superior to conventional criteria (e.g., PGI ≤70 ng/mL and PGI/II ≤3.0), identifying approximately 75% of gastric cancers after eradication.
Long-term proton pump inhibitor (PPI) use has also emerged as a potential risk factor. Cheung et al. [124] reported increasing cancer risk with duration (HR 5.0 at >1 year, 6.7 at >2 years, 8.3 at >3 years). Supporting this, a Korean study reported a significant increased risk (HR 2.22) associated with PPI use of at least 180 days [125]. However, there were also studies that showed that PPIs did not increase the risk of gastric cancer compared to histamine receptor blockers [126]. While observational studies have reported elevated gastric cancer risks with prolonged PPI therapy, it is important to note that these studies demonstrate association rather than proven causality. Several factors complicate the interpretation. Residual confounding factors, such as underlying gastric pathology that necessitates PPI use, may explain the observed risk. Therefore, the clinical significance of this association requires careful interpretation and further investigation.

Treatment of Gastric Cancer after H. pylori Eradication
Although gastric cancers developing after H. pylori eradication may differ in features and prognosis, treatment principles are similar to those before eradication. In a multicenter study, Ikeda et al. [127] reported that early gastric cancers in eradicated patients were smaller, more often flat/depressed, and predominantly differentiated. Despite diagnostic challenges, ESD outcomes were comparable to non-eradicated cases. Specifically, there were no significant differences between the eradication and non-eradicated groups in terms of en bloc resection rate (100% vs. 99.6%), complete resection rate (98.5% vs. 98.4%), curative resection rate (91.5% vs. 89.0%), or median procedure time (56 min vs. 60 min). These findings suggest that H. pylori eradication status does not significantly affect the technical feasibility or short-term outcomes of ER. Successful eradication has been reported to reduce the risk of malignant transformation in gastric dysplasia and improve resection margin delineation when performed in patients with H. pylori infection [128].

Surveillance after H. pylori Eradication
Although eradication is an effective approach to reduce the risk of both primary and metachronous gastric cancers, a residual risk persists, making regular endoscopic surveillance advisable. Surveillance strategies should be risk adapted based on precancerous conditions such as the extent and severity of AG and intestinal metaplasia. Severe atrophy and IM are strong predictors of cancer risk, and the same criteria should be applied to patients after H. pylori eradication. Despite limited prospective studies and RCTs, triennial surveillance is recommended but should be guided by individual risk assessment [129]. Individuals classified as OLGA stages III–IV are considered at high risk and should consider regular long-term endoscopic surveillance [30]. The ESGE and AGA recommend surveillance every 3–5 years for high-risk patients with intestinal metaplasia [130, 131].
In patients with early gastric cancer (EGC), eradication markedly reduces metachronous cancer after ER [132–134]. Notably, patients who developed EGC after eradication had a 5-year cumulative incidence of metachronous cancer of 30.9%, significantly higher than in non-eradicated patients or those eradicated after ESD [127]. After curative ER (R0 with histologically curative criteria), routine short-interval endoscopy solely to confirm local recurrence (e.g., 3- or 6-month checks) is usually unnecessary; instead, annual endoscopic follow-up is recommended to detect metachronous gastric cancer [135]. Regarding surveillance duration, evidence is mixed: some reports suggest a decrease in metachronous risk beyond 10 years, but a larger cohort with longer follow-up showed a continued increase in incidence with several metachronous gastric cancer-related deaths, supporting prolonged or risk-adapted surveillance rather than a fixed stopping point. Early site-directed inspection remains warranted in exceptions (e.g., non-curative resection, uncertain margins, piecemeal resection, or endoscopic/histological concern for residual disease) [136].
The timing of cancer detection after eradication varies widely, ranging from several months to more than a decade [97, 137]. The risk of developing gastric cancer was 0.30% per year [137]. In a prospective study, Kamada et al. [87] observed a 1.1% cancer incidence over 4.5 years in 1,787 patients. Moreover, invasive cancers detected 10 years after eradication often showed aggressive features, supporting surveillance beyond a decade [138]. Gastric cancers detected within the first year after eradication may represent missed lesions from previous endoscopic examinations [139], highlighting the need for careful endoscopic surveillance during the first year after eradication [140].

Conclusion
Although H. pylori eradication reduces gastric cancer risk, a residual risk remains, particularly in patients with persistent AG and intestinal metaplasia. Gastric cancers after eradication show distinctive endoscopic, histopathological, and molecular characteristics, which complicate early detection. Therefore, risk stratification and tailored surveillance strategies are warranted, along with the application of advanced endoscopic technologies and molecular biomarkers. Risk stratification should incorporate the extent of AG (OLGA staging), presence and extent of intestinal metaplasia, family history of gastric cancer, age at eradication, and eradication status; corresponding strategies may include annual endoscopy for high-risk patients, biennial surveillance for intermediate risk, and individualized follow-up for low-risk patients, with comorbidity and life expectancy explicitly considered. These proposals align with contemporary risk-based guidance while acknowledging the limited prospective evidence base. Long-term, individualized management is necessary even after successful eradication. Future research should focus on identifying predictive biomarkers and refining surveillance strategies to further improve prevention and outcomes.

Conflict of Interest Statement
The authors have no conflicts of interest to declare.

Funding Sources
This work was supported by the Korean Ministry of Education, Science and Technology (2019R1A5A2027588 and 2022R1A2C2008281) and the Ministry of Health and Welfare, Republic of Korea (Grant No. HA23C0266).

Author Contributions
Study concept and design: J.M.P. Drafting of the manuscript: S.M. and J.M.P. Critical revision of the manuscript for important intellectual content: I.K., D.K., Y.K.C., and J.M.P. Final approval of the manuscript: all authors.