Preoperative Radiotherapy in Patients with Gastric and Gastro-Oesophageal Cancer: A Systematic Review and Meta-analysis

Background Gastric (GC) and gastroesophageal junction (GEJ) cancers are among the most prevalent digestive cancers, characterized by a poor prognosis, particularly in advanced stages, where the 5-year survival rate remains below 20%. While surgery is still the standard treatment, its limited ability to lower recurrence rates highlights the necessity for effective perioperative therapies. In this context, Radiotherapy (RT) and chemoradiotherapy (CRT) have been investigated for their potential to improve tumor control, pathologic complete response (pCR), and overall survival (OS) in advanced GC. This systematic review and meta-analysis aimed to assess the efficacy and safety of preoperative RT/CRT on key clinical outcomes in patients with GC, focusing on pathologic complete response (pCR), overall survival (OS), and postoperative complications, such as anastomotic leaks and postoperative mortality. Methods A systematic search of PubMed, Embase, and Web of Science databases was conducted for randomized controlled trials and single-arm studies comparing preoperative RT/CRT with chemotherapy or surgery alone. Outcomes were pooled using risk ratios (RRs) or hazard ratios (HRs) with 95% confidence intervals (CIs), and heterogeneity was assessed using I-2 statistics. Furthermore, quality assessment was performed using RoB 2 and ROBINS-I tools. We also utilized tools to enhance the interpretation and understanding of the meta-analysis results, including GRADE, the leave-one-out method, Baujat and Doi plots. Results Ten studies including 6 RCTs and 4 single-arm studies, comprising 2,138 patients were included. CRT significantly improved pCR rates compared to control groups (RR 2.72; 95% CI 1.89-3.92; p < 0.000001; I-2 = 0%), with a pCR rate of 21% in single-arm analysis. No statistical significance was observed in the hazard ratio analysis for OS (HR 0.84; 95% CI 0.65-1.10; p = 0.209; I-2 = 67%), including the subgroup analyses at three (RR 1.15; 95% CI 0.93-1.43; p = 0.183; I-2 = 70%) and five years (RR 1.23; 95% CI 1.00-1.51; p = 0.051; I-2 = 58%). Moreover, the rates for anastomotic leaks (RR 0.86; 95% CI 0.66-1.14; p = 0.294; I-2 = 0%) and postoperative mortality (RR 0.88; 95% CI 0.46-1.70; p = 0.71; I-2 = 25%) showed no significant differences between groups, with low event rates in single-arm studies, 7% and 3%, respectively. Conclusion Preoperative CRT significantly improves pCR rates, highlighting its potential as a valuable strategy in tumor downstaging. However, it does not enhance survival outcomes, while notably, it does not increase surgical complications. Future studies incorporating biomarkers and standardized protocols are essential to refine patient selection, ensuring optimized treatment strategies and maximizing clinical benefits.