Adjuvant chemoradiotherapy versus radiotherapy alone in high-risk endometrial cancer: A systematic review and meta-analysis

Abstract

Background: The benefits of adjuvant chemoradiotherapy (CRT) for high-risk endometrial cancer (HREC) in International Federation of Gynecology and Obstetrics (FIGO) stages I-III remain controversial. A systematic review and meta-analysis was conducted to evaluate the clinical effectiveness and safety of postoperative CRT over radiotherapy (RT) alone, exclusively for patients with HREC for the following key endpoints: overall survival (OS), progression-free survival (PFS), the local recurrence rate, the distant metastasis rate, cancer-specific survival (CSS), grade III/IV acute and late toxicities, and the small bowel obstruction rate.

Methods: Five databases, namely, PubMed, EMBASE, Cochrane Library, Web of Science and ClinicalTrials.gov, were systematically explored and supplemented by manual searching to identify relevant studies published before Dec 9, 2017. Only prospective randomized controlled trials (RCTs) conducted for HREC comparing CRT and RT alone after surgery were included. All statistical analyses were performed using RevMan Version 5.3 software.

Results: Six eligible trials involving 2105 patients were identified for the final meta-analysis (CRT: n = 1064; RT: n = 1041). No statistically significant differences were evident between the CRT and RT groups regarding OS (n = 2105, RR = 1.02, 95% CI 0.98-1.06, P = 0.40). Additionally, no differences were apparent in terms of the local recurrence rate (n = 690, RR = 0.48, 95% CI 0.19-1.18, P = 0.11) or distant metastasis rate (n = 1445, RR = 0.94, 95% CI 0.72-1.23, P = 0.67). However, CRT significantly prolonged overall five-year PFS (80.2% vs. 74.5%, +5.7%; RR = 1.08, P = 0.005) and five-year CSS (86.1% vs. 79.0%, +7.1%; RR = 1.09, P = 0.03). A higher incidence of grade III/IV toxicities (P < 0.00001) was evident with CRT, while grade III/IV late toxicities and the small bowel obstruction rate were not significantly different between the two groups.

Conclusions: For patients with endometrial cancers with stage I-III risk factors, adjuvant CRT can significantly improve PFS and CSS compared with RT. With the exception of increased acute toxicities, CRT is well accepted and tolerated in HREC patients.

Keywords: Chemoradiotherapy; Endometrial cancer; Meta-analysis; Radiotherapy; Systematic review.