Improvement of survival in advanced gastric cancer over 15 years: real-world analysis by 5-year periods

Background Although immunotherapy and molecular targeted agents have been introduced for advanced gastric cancer (AGC), it remains unclear whether these therapeutic advances have translated into improved survival outcomes in real-world settings. Patients and methods We conducted a retrospective cohort study of patients with advanced gastric or oesophagogastric junction adenocarcinoma who received first-line chemotherapy. Patients were stratified into three chronological periods: A (2009-2014), B (2014-2019), and C (2019-2024). Overall survival (OS) was the primary endpoint. Multivariable Cox proportional hazards models were used to evaluate independent prognostic factors. Results Of the 677 screened patients, 322 were eligible. The baseline characteristics were generally comparable across periods, although the median age was slightly higher in period C than in periods A and B. The use of immune checkpoint inhibitors and molecular targeted agents increased substantially in period C. The median OS sequentially improved: 9.2, 10.7, and 13.6 months in A, B, and C, respectively. Subgroup analyses showed no significant improvement in the OS of patients with peritoneal metastasis. Patients with performance status (PS) 1-2 achieved significantly improved OS, whereas those with PS 0 showed only a modest trend. Multivariable analysis confirmed that a later treatment period was an independent favourable factor, with a significant benefit in C versus A. Conclusions Survival outcomes of patients with AGC improved over time in real-world settings, consistent with the trends observed in clinical trials. However, the lack of improvement in patients with peritoneal metastasis highlights a critical unmet need for this subgroup.