Adjuvant sandwich therapy is associated with improved survival in stage III–IVA endometrial cancer: a network meta-analysis

Objective: Patients with advanced endometrial cancer (International Federation of Gynecology and Obstetrics stages III-IVA) face a high risk of recurrence even after surgery.Although adjuvant chemoradiotherapy (CRT) is standard care, the optimal sequencing strategy remains controversial.This research aimed to evaluate the impact of 4 CRT sequencing strategies on survival in patients with stages III-IVA endometrial cancer.Methods: We conducted a network meta-analysis of 9 studies, encompassing 8,401 patients, to compare 4 CRT regimens: concurrent CRT (CCRT), chemotherapy followed by radiotherapy (CR), radiotherapy followed by chemotherapy (RC), and sandwich therapy involving chemotherapy-radiotherapy-chemotherapy (CRC).The primary outcomes were overall survival (OS) and progression-free survival (PFS), which were analyzed using risk ratios (RRs) with 95% confidence intervals (CIs).Treatment rankings were determined based on surface under the cumulative ranking (SUCRA) probabilities.Results: CRC demonstrated superior survival outcomes compared to other regimens, with significantly higher mortality risks observed in comparator groups: for OS, CCRT showed a 99% increased risk (RR=1.99;95% CI=1.28-3.09),CR 48% (RR=1.48;95% CI=1.11-1.97),and RC 57% (RR=1.57;95% CI=1.09-2.26);for PFS, CR exhibited 40% higher recurrence risk (RR=1.40;95% CI=1.16-1.68)and RC 35% (RR=1.35;95% CI=1.03-1.77).SUCRA values ranked CRC highest for both OS (92.98%) and PFS (96.32%), with no significant differences in grade 3 toxicity across regimens. Conclusion:For patients with stages III-IVA endometrial cancer, CRC is associated with survival benefits without an increase in toxicity.Pending prospective validation, these findings support CRC as the preferred adjuvant regimen.