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

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.

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.

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.

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.