Comparison of outcomes between surgery and non-surgery after conversion therapy for advanced gastric cancer with unresectable factors: a systematic review and meta-analysis.

Background: Advanced gastric cancer (AGC) with unresectable factors presents a significant treatment challenge. Conventional treatments such as systemic chemotherapy, radiotherapy, and immunotherapy can delay disease progression but often yield limited outcomes. For stage III-IV gastric cancer with unresectable factors, conversion therapy based on chemotherapy can achieve tumor downstaging, providing a subset of patients with the opportunity for curative surgery. However, the efficacy of multimodal approaches combining chemotherapy, with or without immunotherapy, and conversion surgery compared to chemotherapy alone remains controversial.

Methods: We conducted a systematic review and meta-analysis of high-quality studies published between January 2014 and November 2024, assessing the role of surgery following conversion therapy in advanced gastric cancer. Relevant studies were retrieved from PubMed, Embase, and Web of Science databases. All included studies were observational; no randomized trials were available. Clinical data, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and adverse event (AE) rates, were analyzed using RevMan 5.4.

Results: Twelve observational cohort studies were included. Conversion surgery(CS) was associated with improved 1-year, 3-year, and 5-year OS rates (RR 0.38, 95% CI: 0.31-0.47; RR 0.64, 95% CI: 0.54-0.76; RR 0.77, 95% CI: 0.65-0.91, respectively) and increased 1-year and 3-year PFS rates (RR 0.57, 95% CI: 0.49-0.99; RR 0.67, 95% CI: 0.57-0.78, respectively). No significant difference in AE rates was observed between groups.

Conclusions: Conversion surgery following chemotherapy in stage III-IV gastric cancer is associated with improved OS and PFS in observational studies. However, these findings may reflect inherent prognostic differences between groups, as surgery was only feasible for chemotherapy responders. Prospective trials are needed to validate causality.