Efficacy of Fertility-Sparing Treatment With Progestin Is Associated With Different Molecular Classification in...

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).

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.

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).

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.