Neoplastic Progression Risk in Females With Barrett’s Esophagus: A Systematic Review and Meta-Analysis of Individual Patient Data

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Females with Barrett's esophagus (BE) have a lower risk of neoplastic progression than males, but sufficiently powered risk analyses are lacking. This systematic review and meta-analysis of individual patient data (IPD) aimed to provide more robust evidence on neoplastic progression risk in females. We conducted a systematic literature search of 3 electronic databases (Medline, Embase, Google Scholar) from inception until August 2023. Eligible studies (1) reported original data on progression from nondysplastic BE, indefinite for dysplasia, or low-grade dysplasia to high-grade dysplasia or esophageal adenocarcinoma; and (2) included female and male patients. IPD were quality controlled by 2 independent reviewers. The primary outcome was the association between sex and neoplastic progression risk, adjusted for risk factors using multivariable Cox regression analysis. Secondary outcomes were sex differences in time to progression and annual progression rate. IPD were obtained from 11 of 66 eligible studies, including 2196 (31%) females. Neoplastic progression risk was lower in females (hazard ratio for males vs females, 1.44; 95% confidence interval, 1.13-1.82) after adjusting for age, smoking, medication use, hiatal hernia, BE length, and baseline pathology. The annual progression rate was 0.88% in females vs 1.29% in males. Time to progression was similar in both sexes: 3.7 years (interquartile range, 2.1-7.7 years) in females and 4.2 years (interquartile range, 2.0-8.1 years) in males. Although females had a lower neoplastic progression risk, sex differences were smaller than previously reported, and time to progression was similar for both sexes. Future research should focus on other factors than sex to identify low- and high-risk BE patients.