Effects of a fertility-sparing re-treatment for recurrent atypical endometrial hyperplasia and endometrial cancer: a systematic literature review

Isao Murakami; Hiroko Machida; Tohru Morisada; Yasuhisa Terao; Tsutomu Tabata; Mikio Mikami; Yasuyuki Hirashima; Yoichi Kobayashi; Tsukasa Baba; Satoru Nagase

doi:10.3802/jgo.2023.34.e49

Effects of a fertility-sparing re-treatment for recurrent atypical endometrial hyperplasia and endometrial cancer: a systematic literature review

J Gynecol Oncol. 2023 Jul;34(4):e49. doi: 10.3802/jgo.2023.34.e49. Epub 2023 Mar 6.

Authors

Affiliations

¹ Department of Obstetrics and Gynecology, Toho University Ohashi Medical Center, Tokyo, Japan. [email protected].
² Department of Obstetrics and Gynecology, Tokai University School of Medicine, Isehara, Japan.
³ Department of Obstetrics and Gynecology, Kyorin University Faculty of Medicine, Tokyo, Japan.
⁴ Department of Obstetrics and Gynecology, Faculty of Medicine, Juntendo University, Tokyo, Japan.
⁵ Department of Obstetrics and Gynecology, Tokyo Women's Medical University, Tokyo, Japan.
⁶ Division of Gynecology, Shizuoka Cancer Center, Shizuoka, Japan.
⁷ Department of Obstetrics and Gynecology, Iwate Medical University, Iwate, Japan.
⁸ Department of Obstetrics and Gynecology, Yamagata University Faculty of Medicine, Yamagata, Japan.

^# Contributed equally.

Abstract

Objective: To examine the effectiveness of progestin re-treatment for recurrent endometrial intraepithelial neoplasia (EIN), atypical endometrial hyperplasia (AH) and endometrial cancer (EC) following initial fertility-sparing treatment.

Methods: A comprehensive systematic review and meta-analysis were conducted by an Expert Panel of the Japan Society of Gynecologic Oncology Endometrial Cancer Committee. Multiple search engines, including PubMed/MEDLINE and the Cochrane Database, were searched in December 2021 using the keywords "Endometrial neoplasms," "Endometrial hyperplasia," "Endometrial intraepithelial neoplasia," "Fertility preservation," "Progestins," AND "Recurrence." Cases describing progestin re-treatment for recurrent EIN, AH and EC were compared with cases that underwent conventional hysterectomy. The primary outcomes were survival and disease recurrence, and the secondary outcome was pregnancy.

Results: After screening 238 studies, 32 with results for recurrent treatment were identified. These studies included 365 patients (270 received progestin re-treatment and 95 underwent hysterectomy). Most progestin re-treatment involved medroxyprogesterone acetate or megestrol acetate (94.5%). Complete remission (CR) following progestin re-treatment was achieved in 219 (81.1%) cases, with 3-, 6- and 9-month cumulative CR rates of 22.8%, 51.7% and 82.6%, respectively. Progestin re-treatment was associated with higher risk of disease recurrence than conventional hysterectomy was (odds ratio [OR]=6.78; 95% confidence interval [CI]=1.99-23.10), and one patient (0.4%) died of disease. Fifty-one (14.0%) women became pregnant after recurrence, and progestin re-treatment demonstrated a possibility of pregnancy (OR=2.48; 95% CI=0.94-6.58).

Conclusion: This meta-analysis suggests that repeat progestin therapy is an effective option for women with recurrent EIN, AH and EC, who wish to retain their fertility.

Keywords: Endometrial Hyperplasia; Endometrial Neoplasm; Fertility Preservation; Progestins; Recurrence.

Publication types

Systematic Review
Meta-Analysis

MeSH terms

Endometrial Hyperplasia* / drug therapy
Endometrial Neoplasms* / drug therapy
Female
Fertility Preservation* / methods
Humans
Neoplasm Recurrence, Local
Pregnancy
Progestins / therapeutic use
Retrospective Studies
Treatment Outcome

Substances

Progestins