REN Qian, ZHANG Lijuan, XUE Yu, LU Danhua, WANG Weina, LIU Chunhong, WANG Yifei, FU Yuanyuan, SUN Yuefang, JI Guo, HUANG Qiongyi, ZHENG Jiayi, ZHU Huiting, SHAN Weiwei, CHEN Xiaojun
Objective To explore the efficacy of fertility-preserving therapy (FST) in patients with POLE ultra-mutant (POLEmut) endometrial carcinoma (EC)/endometrial atypical hyperplasia (EAH), and to compare the therapeutic effects between theprogestogen/gonadotropin-releasing hormone agonist (GnRH-a) and immune checkpoint inhibitors (ICIs) regimens. Methods Clinical data of POLEmut EC/EAH patients who received FST were collected retrospectively at Obstetrics and Gynecology Hospital of Fudan University and Shanghai Tenth People's Hospital of Tongji University from April 2019 to November 2025. They were divided into progestogen/GnRH-a group (n=8) and ICIs group (n=5). Therapeutic, follow-up and pregnancy outcomes were compared between groups. Results Among the 13 patients, 7 cases underwent off-indication FST, and 5 cases in the ICIs group were off-indication. There was no significant difference in the complete response (CR) rate between the two groups (P=1.000). The median CR time in the ICIs group (28.2 weeks) was shorter than that in the progestogen/GnRH-a group (35.9 weeks, P=0.450). There were 4 refractory cases, including 3 in the progestogen/GnRH-a group and 1 case in the ICIs group, with no statistical difference (P=1.000). The median total follow-up time and post-CR follow-up time in the ICIs group were significantly shorter than those in the progestogen/GnRH-a group (median 21.1 months vs 44.6 months, 14.0 months vs 33.8 months, both P<0.05). No recurrence was observed in the ICIs group, while 2 cases of recurred were in the progestogen/GnRH-a group (P=0.467). Among the 8 CR patients, 7 achieved successful pregnancy, including 5 cases in the progesterone/GnRH-a group, all of which resulted in successful pregnancies with 4 live births; 2 cases in the ICIs group achieved successful pregnancy, both of which were in the third trimester. Conclusion Both progestogen/GnRH-a and ICIs regimens are effective for FST in POLEmut EC/EAH patients. With all ICIs patients undergoing off-indication FST, the ICIs regimen shows a trend of faster onset, better short-term disease control and favorable pregnancy outcomes, which may be a preferred FST option.