OLGA STAGE II IS A SIGNIFICANT RISK FACTOR FOR GASTRIC CANCER: A SYSTEMATIC REVIEW AND META-ANALYSIS EMPHASISING INTERMEDIATE HISTOLOGICAL STAGES

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Introduction

Gastric cancer (GC) is the fifth most common malignancy worldwide and the fourth leading cause of cancer death. In Colombia, it ranks third in incidence and first in mortality, with a 5-year survival below 25% in advanced stages. Early detection relies on identifying premalignant lesions. OLGA and OLGIM histological staging systems enable risk stratification. While stages III–IV are known high-risk states, the role of stage II remains unclear. This study focuses on OLGA II to address this gap.

Aims & Methods

This systematic review and meta-analysis, registered on PROSPERO (CRD42024549931), adhered to PRISMA 2020 guidelines. The primary objective was to determine whether OLGA stage II confers a statistically significant risk of GC compared to stages 0–I. Secondary objectives included evaluating risks across all advanced stages (II–IV) and contrasting OLGA versus OLGIM staging.
We searched PubMed, EMBASE, and Cochrane up to 31 May 2024 using terms including "OLGA", "OLGIM", "gastric cancer", and "gastric intraepithelial neoplasia". Inclusion criteria covered cohort, case-control, and cross-sectional studies reporting GC incidence stratified by OLGA/OLGIM stage. Data extraction and quality assessment were performed independently by two reviewers using the Newcastle-Ottawa Scale, with evidence certainty assessed via GRADE. Meta-analytical synthesis used random-effects modelling, and heterogeneity was assessed with I² and Tau² statistics.

Results

Twenty-eight studies met inclusion criteria, comprising 13 cohort, 11 case-control, and 4 cross-sectional studies.

OLGA II vs 0–I (Cross-sectional studies): A significantly increased GC risk was observed (Z = 3.14; P = 0.002; I² = 65%), suggesting OLGA II as an early but meaningful predictor of malignant transformation.
OLGA II (Cohort studies): No statistically significant difference was found (P = 0.28; I² = 0%), though sample size was limited.
OLGIM II: Demonstrated increased risk only in case-control settings (Z = 11.26; P < 0.00001), but not in cohort studies.

Findings for OLGA and OLGIM stages III–IV corroborated existing evidence of elevated risk. However, this is the first meta-analysis to demonstrate a potential oncogenic risk beginning at OLGA stage II, particularly evident in cross-sectional data.
Sensitivity analyses affirmed result consistency, and the certainty of evidence was rated moderate. Subgroup comparisons revealed that OLGA may outperform OLGIM in early risk discrimination.

Table 1. Summary of Gastric Cancer Risk According to OLGA and OLGIM Stages

Staging System	Stage	Study Design	Pooled Risk Estimate	95% CI	Heterogeneity (I²)	Significance (p-value)
OLGA	II vs 0–I	Cross-sectional	OR 2.34	1.36 – 4.02	65%	0.002
OLGA	II vs 0–I	Cohort	RR 1.20	0.85 – 1.69	0%	0.28
OLGA	III–IV vs 0–II	Case-control & Cohort	OR 4.87 / RR 3.12	–	88%	< 0.00001
OLGIM	II vs 0–I	Case-control	OR 1.95	1.52 – 2.50	0%	< 0.00001
OLGIM	II vs 0–I	Cohort	RR 1.10	0.85 – 1.42	0%	0.74
OLGIM	III–IV vs 0–II	Case-control & Cohort	OR 3.89 / RR 2.91	–	82%	< 0.00001

Abbreviations: OR = Odds Ratio; RR = Risk Ratio; CI = Confidence Interval

Conclusion

Our study highlights a pivotal finding: OLGA stage II—previously considered an intermediate state—emerges as a statistically significant risk factor for gastric cancer. These findings suggest that the progression to malignancy may begin earlier than currently recognised. Incorporating OLGA II into surveillance strategies could lead to improved early detection, especially in high-incidence countries. The data support a shift toward broader inclusion criteria for endoscopic follow-up and reinforce the clinical utility of histological staging in GC prevention frameworks.

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