Efficacy of Fertility‐Sparing Treatment With Progestin Is Associated With Different Molecular Classification in Endometrial Carcinoma and Atypical Endometrial Hyperplasia

OBJECTIVE: To investigate the impact of various molecular characteristics on the outcomes of fertility-preserving therapy in patients with endometrial cancer (EC) and atypical endometrial hyperplasia (AEH). METHODS: A total of 14 EC cases and 60 AEH cases were retrospectively analyzed at the Women's Hospital, Zhejiang University from January 2013 to October 2022. RESULTS: This study investigated the molecular profiles and outcomes of fertility preservation in 74 cases. The most prevalent molecular profile was NSMP type (63.9%), followed by p53abn type (21.3%) and MMRd type (14.8%). After 6 months of progesterone therapy, the cumulative CR rates were 100% for NSMP type, 83.3% for MMRd type, and 33.3% for p53abn type (p = 0.006). The CR rate in the p53abn group was significantly lower than in the other two groups (p = 0.006), with a notably higher recurrence rate (p = 0.006). ER and PR expression was significantly lower in the MMRd and p53abn groups (p = 0.002). A total of 26 pregnancies (42.6%) were observed. In the EC group, the pregnancy rate of p53abn was lower than that of the NSMP group (0% vs. 83.3%, p = 0.02). In the AEH group, pregnancy rates of p53abn and MMRd were not significantly different from the NSMP group (0% vs. 50%, p = 0.16; 33.3% vs. 50%, p = 0.20). CONCLUSION: Molecular classification may serve as a predictive tool for the efficacy of fertility preservation therapy in patients with EC and AEH and was found to be particularly useful for identifying p53 mutants, which are associated with a high risk of recurrence, as well as MMRd types, which are known to lead to poor responses to progesterone treatment.