The majority of patients with advanced esophageal or gastric cancer do not start palliative systemic treatment. To gain insight into the considerations underlying the decision not to start systemic treatment, we analyzed characteristics of patients starting and not starting systemic treatment, reasons for not starting systemic treatment, and receipt of local palliative treatments on a nationwide scale. Patients diagnosed with advanced esophageal or gastric cancer between 2015 and 2021 were included (n = 10,948). Survival was compared using propensity score matching on patient and disease characteristics. Most patients did not start systemic treatment (esophageal cancer 59%
gastric cancer 64%). These patients were generally older, more often female, had more comorbidities and a worse performance status. The main reason for not starting systemic treatment was patient or family preference (35%). Among patients who did not start systemic treatment, 47% (esophageal) and 19% (gastric), received local palliative treatment, most commonly radiotherapy. Patients who did not start systemic treatment had worse median overall survival compared to patients who did start (esophageal cancer 2.9 months vs. 8.9 months
gastric cancer 2.2 vs. 8.2 months). These findings indicate that patient condition and disease burden are important aspects in systemic treatment decisions. However, patient or family preference was the main reason for not starting systemic treatment, highlighting that their priorities also strongly influence the decision. Systemic treatment did show to be associated with improved overall survival in matched patients, and therefore adequately weighing treatment risks and benefits based on real world data against patient preferences is of utmost importance.