Introduction
Post-endoscopy upper gastrointestinal cancers (PEUGIC) - malignancies diagnosed within three years of a cancer-negative endoscopy - represent a significant but poorly quantified diagnostic gap in upper gastrointestinal (UGI) cancer care. Late presentation limits treatment options and drives poor survival; PEUGIC reflects missed or sub-optimally characterised lesions at index endoscopy, and may in part be avoidable.
Aims & Methods
To determine the pooled proportion of PEUGIC among all diagnosed upper gastrointestinal (UGI) cancers, to describe variation by geographic region, time period and cancer site, and to identify study-, population- and participant-level factors influencing this proportion.
We conducted a systematic review and meta-analysis (PROSPERO CRD42024543642) of MEDLINE, Embase and Cochrane Central were searched (January 2000–July 2026) for cohort, case-control and cross-sectional studies reporting PEUGIC rate (PEUGIC/total UGI cancers). Two reviewers independently screened studies, extracted data (study characteristics, PEUGIC definitions, cancer site, and participant demographics), and assessed risk of bias using a modified Newcastle-Ottawa scale, with disagreements resolved by a third reviewer. Proportions were pooled using a random-effects model with Freeman-Tukey double arcsine transformation and restricted maximum likelihood estimation. Heterogeneity was quantified using I² and H² statistics. Subgroup analyses, leave-one-out sensitivity analysis, and univariate/multivariable meta-regression were performed to explore heterogeneity by region, cancer site, endoscopy indication, recruitment/publication period and study quality. Publication bias was assessed using Doi plots, the LFK index and Egger's test.
Results
53 studies comprising 4,831,380 participants and over 7.1 million endoscopies were included, yielding 215,544 UGI cancers, with a PEUGIC rate of 9.92% (95% CI 8.07–11.93%). Heterogeneity was considerable (I²=99.3%), though leave-one-out analysis showed no single study substantially altered the pooled estimate. The pooled median diagnostic interval was 16.2 months. Rates varied significantly by WHO region (Western Pacific 13.2%, Europe 9.1%, Americas 8.2%; p<0.005). Endoscopy indication was also a strong driver: gastric cancer screening populations had the highest rate (18.9%), followed by Barrett's surveillance cohorts (12.6%) and unselected populations (8.2%; p<0.005). Barrett's oesophagus cohorts showed a higher pooled PEEC rate than non-Barrett's unselected cohorts (13.7% vs 7.4%; p<0.005). Cancer site (gastric 10.3%, oesophageal 8.4%, duodenal 11.2%), definitional time window (12 vs 24 vs 36 months), publication year, recruitment period and Newcastle-Ottawa quality score were not significant predictors. On multivariable meta-regression, only gastric cancer screening indication independently predicted a higher PEUGIC rate (risk difference +9.8%, p=0.026). Doi plots suggested possible small-study effects for the overall and oesophageal subgroups (LFK index 2.1 and 3.5 respectively), though Egger's test was non-significant throughout.
Conclusion
Approximately 1 in 10 UGI cancers are diagnosed within three years of a cancer-negative endoscopy. Mean delays in diagnosis (assuming detectable disease at index) are 16 months. Variability in PEUGIC rates across regions, populations, and cancer sites suggests unwarranted variation and avoidable cases. Global quality improvement efforts are required to reduce PEUGIC rates and improve early diagnosis.
References
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