The association of molecular classification with fertility-sparing treatment of atypical endometrial hyperplasia and endometrial carcinoma：A retrospective study

Yuanyuan Wang ^1,2 Tianjiao Lai ¹ Danxia Chu ¹ Jing Bai ¹ Shuping Yan ¹ Ruixia Guo ^1*

• ¹ First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
• ² The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan Province, China

Background: To evaluate whether molecular classification was associated with treatment response and recurrence in women with atypical endometrial hyperplasia (AEH) or early-stage endometrial cancer (EC) treated with progestin.Methods: A retrospective analysis of 116 patients (71 AEH and 45 EC) who received fertilitysparing therapy between 2010 and 2022 was performed. Tumors were classified via immunohistochemistry and gene sequencing into four subgroups: POLE-mutated (POLEmut), p53 wild type (p53 wt/NSMP), mismatch repair deficient (MMRd), and p53-abnormal (p53abn). The primary outcome was complete response (CR) to hormonal therapy. Secondary outcomes included the recurrence rate after CR and conception success. The treatment response to progestin and recurrence rate were compared across four subgroups.Results: Of 116 patients, 10 (8.62%) were classified as POLEmut, 81 (69.82%) p53 wt, 9 (7.76%) p53abn, 16 (13.76%) MMRd. At 12 months evaluation, 87 patients (75.00%) achieved CR (median treatment duration: 5.95 months; range: 1.6-12.9). Partial response (PR), stable disease (SD), and progressive disease (PD) rates were 6.89% (n=8), 1.72% (n=2), and 16.38% (n=19), respectively.Patients with the p53abn and MMRd subtype had a lower CR rate (33.33%, 37.50%) and a higher progression rate (44.40%, 37.50%) compared to other subgroups (P<0.05). After 24-month follow-up, recurrence rates were markedly higher in p53abn (100%) and MMRd (83.33%) versus POLEmut (33.33%) and p53 wt (17.39%) subgroups (P<0.05). Among 56 (64.37%) patients attempting conception, the pregnancy rate of 38 patients who received in vitro fertilization-embryo transfer was 47.37%(18/38), and the pregnancy rate of 18 patients who chose natural pregnancy was 16.67%(3/18), showing no statistical difference (P=0.072).Conclusion: Molecular classification may be associated with hormonal treatment response in patients with AEH and EC patients with POLEmut and p53wt had better progestin response, MMRd and p53abn had the poorest response and the highest recurrence rate. Recurrence was common after CR, and close review was necessary. For further investigating the role of molecular classification in fertility-sparing treatment of AEH/EC , larger prospective studies were necessary.