Real-world insights into young-onset gastroesophageal adenocarcinoma: an all-Ireland population-based cancer registry analysis

Background
Population-based studies report a rising incidence of young-onset (YO) oesophageal and gastric cancer. We examined clinicopathological features, treatment, and outcomes in YO (18-50 years), midlife-onset (MO, 50-70 years), and late-onset (LO, >70 years) oesophageal and gastric adenocarcinoma.

Methods
Population-based data were collected from the National Cancer Registry Ireland (NCRI) and Northern Ireland Cancer Registry (NICR). Incidence trends were determined using Joinpoint regression. Kaplan-Meier curves, log-rank tests, and multivariable Cox regression were used to assess survival differences. Multivariable Cox regression was adjusted for key clinical covariates, and excluded patients with missing covariates.

Results
We analysed 21 706 patients diagnosed with oesophageal or gastric adenocarcinoma from 1999 to 2022. YO gastric tumours were more diffuse (YO 26.6% versus MO 13.8% versus LO 10.4%, P < 0.001) and poorly differentiated (YO 60.6% versus MO 56.4% versus LO 55.0%, P < 0.0001); and presented more frequently with stage IV disease (YO 53.7% versus MO 46.4% versus LO 44.6%, P < 0.001). Incidence rates increased significantly across all age groups for lower oesophageal cancer: YO [average annual percentage change (AAPC) 2.6%, 95% confidence interval (CI) 1.1% to 4.3%], MO (AAPC 3.3%, 95% CI 2.4% to 4.4%), and LO (AAPC 2.1%, 95% CI 1.2% to 3.1%). Gastric cancer incidence was stable in YO but declined in the MO (AAPC -2.6%) and LO (AAPC -2.1%) groups. LO had poorer overall survival versus YO [hazard ratio 1.84, 95% CI 1.71% to 1.98%), P < 0.001, multivariable Cox analysis].

Conclusion
Oesophageal adenocarcinoma incidence is rising across all age groups, while gastric adenocarcinoma incidence was stable in the YO population and declining in older adults. Despite more advanced and aggressive disease at presentation, YO patients had better overall survival.