Levonorgestrel-releasing intrauterine system-based therapies for early-stage endometrial cancer: a systematic review and meta-analysis

Objective: To conduct a systematic review and meta-analysis of studies evaluating the oncological and fertility outcomes of early-stage endometrial cancer (EC) treated with the levonorgestrel-releasing intrauterine system (LIUS)-based regimens.

Methods: The Meta-analyses Of Observational Studies in Epidemiology statement for meta-analyses was followed. Searches were conducted on MEDLINE, Embase, PubMed, Preprints, and the Cochrane Central Register of Controlled Trials from January 1990 to August 4, 2022. The Joanna Briggs Institute Critical Appraisal Checklist was used for quality assessment. The primary endpoint was the complete response (CR) rate and the secondary endpoints were relapse, pregnancy, and live birth rate.

Results: A total of 25 studies (821 women) were included. The CR rate of LIUS-based regimens was 63.4% (95% confidence interval [CI]=52.3%-73.2%), with 29.6% (95% CI=23.3%-36.8%) of cases experiencing recurrence during follow-up. In sensitivity analyses, patients younger than 45 years of age with a body mass index <30 kg/m² who were treated with LIUS-based regimens achieved a high CR rate of 84.6% (95% CI=80.3%-88.1%) over a median follow-up of more than 24 months. Overall pregnancy and live birth rates were 37.9% (95% CI=24.1%-53.9%) and 39.3% (95% CI=24.0%-57.0%), respectively. No statistical differences were apparent in CR or relapse rates among the LIUS+GnRH agonist, LIUS+oral progesterone, or hysteroscopic resection followed by LIUS subgroups.

Conclusion: LIUS-based therapies are viable for the conservative management of early-stage endometrioid EC on CR and fertility outcome.

Trial registration: PROSPERO Identifier: CRD42022352890.