Fertility-preserving treatment for stage IA endometrial cancer: a systematic review and meta-analysis

Abstract

Objective: The increasing use of fertility-preserving treatments in reproductive-aged patients with early-stage endometrial cancer necessitates robust evidence on the effectiveness of oral progestins and levonorgestrel-releasing intrauterine device. We conducted a systematic review and meta-analysis to examine the outcomes following these 2 primary progestin-based therapies in reproductive-aged patients with early-stage endometrial cancer.

Data sources: We conducted a systematic review of observational studies and randomized controlled trials following the Cochrane Handbook guidance. We conducted a literature search of 5 databases and 1 trial registry from inception of the study to April 16, 2024.

Study eligibility criteria: Studies reporting complete response within 1 year in reproductive-aged patients with clinical stage IA endometrioid cancer undergoing progestin therapy treatment were included. We used data from both observational and randomized controlled studies.

Study appraisal and synthesis methods: The primary exposure assessed was the type of progestational treatment (oral progestins or LNG-IUD). The primary outcome was the pooled proportion of the best complete response (CR) within 1 year of primary progestational treatment. We performed a proportional meta-analysis to estimate the treatment response. Sensitivity analyses were performed by removing studies with extreme effect sizes or removing grade 2 tumors. The risk of bias was assessed in each study using the Joanna Briggs Institute critical appraisal checklist.

Results: Our analysis involved 754 reproductive-aged patients diagnosed with endometrial cancer, with 490 receiving oral progestin and 264 receiving levonorgestrel-releasing intrauterine device as their primary progestational treatment. The pooled proportion of the best complete response within 12 months of oral progestin and levonorgestrel-releasing intrauterine device treatment were 66% (95% CI, 55-76) and 86% (95% CI, 69-95), respectively. After removing outlier studies, the pooled proportion was 66% (95% CI, 57-73) for the oral progestin group and 89% (95% CI, 75-96) for the levonorgestrel-releasing intrauterine device group, showing reduced heterogeneity. Specifically, among studies including grade 1 tumors, the pooled proportions were 66% (95% CI, 54-77) for the oral progestin group and 83% (95% CI, 50-96) for the levonorgestrel-releasing intrauterine device group. The pooled pregnancy rate was 58% (95% CI, 37-76) after oral progestin treatment and 44% (95% CI, 6-90) after levonorgestrel-releasing intrauterine device treatment.

Conclusion: This meta-analysis provides valuable insights into the effectiveness of oral progestins and levonorgestrel-releasing intrauterine device treatment within a 12-month timeframe for patients with early-stage endometrial cancer who desire to preserve fertility. These findings have the potential to assist in personalized treatment decision-making for patients.

Keywords: endometrial cancer; fertility-preserving treatment; hormonal therapy; levonorgestrel-releasing intrauterine device; progestin.