Efficacy and Toxicity of Adjuvant Therapies for High-Risk Endometrial Cancer in Stage I–III: A Systematic Review and Network Meta-Analysis

BACKGROUND The use of adjuvant therapy for high-risk endometrial cancer patients (HREC) in International Federation of Gynecology and Obstetrics (FIGO) stage I-III remains debatable. This network meta-analysis was conducted to compare and rank adjuvant therapies based on efficacies and toxicities to facilitate clinical decision-making and further research. MATERIAL AND METHODS We searched 3 databases - PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials - from inception to December 9, 2019. Only randomized controlled trials that compared any of these adjuvant therapies (pelvic radiotherapy, vaginal brachytherapy, chemotherapy, and chemoradiotherapy) with each other or surgery alone were included. The network meta-analysis was performed in a frequentist framework using Stata software 15.0. RESULTS Fourteen RCTs with 5872 participants were eligible. No significant difference between treatments was observed in 5-year overall survival (OS) or distant metastasis. Compared with surgery alone, adjuvant pelvic radiotherapy plus chemotherapy (pelvic RT-CT) prolonged 5-year progression-free survival (PFS) and pelvic radiotherapy (pelvic RT) (RR=0.61, 95% CI 0.39-0.96; RR=0.779, 95% CI 0.63-0.95). Compared with surgery alone, pelvic RT, the combination of pelvic RT and vaginal brachytherapy (pelvic RT-VBT), chemotherapy (CT), and pelvic RT-CT led to fewer local recurrences (RR=0.33, 95% CI 0.21-0.50; RR=0.15, 95% CI 0.03-0.74; RR=0.39, 95% CI 0.21-0.73; RR=0.17, 95% CI 0.06-0.46). Adjuvant CT was found to result in more grade III/IV late toxicities than surgery alone (RR=11.8, 95% CI 1.02-137.14). Pelvic RT-CT ranked first for OS, PFS, distant metastasis, and local recurrence. CONCLUSIONS Pelvic RT-CT is superior to other treatments for PFS and local recurrence rate, and associated related toxicities are tolerable, suggesting it may be an ideal adjuvant therapy for HREC patients.