Outcomes of fertility preservation treatments in patients with endometrial cancer with different molecular classifications based on an NGS panel

Yan Xu; Mingming Zhao; Li Zhang; Tianyou Wang; Bo Wang; Yu Xue; Zhiying Xu; Wenyu Shao; Xiaojun Chen; Chao Wang

doi:10.3389/fonc.2023.1282356

Outcomes of fertility preservation treatments in patients with endometrial cancer with different molecular classifications based on an NGS panel

Front Oncol. 2023 Nov 9:13:1282356. doi: 10.3389/fonc.2023.1282356. eCollection 2023.

Authors

Yan Xu^#¹, Mingming Zhao^#¹, Li Zhang¹, Tianyou Wang¹, Bo Wang¹, Yu Xue¹, Zhiying Xu¹, Wenyu Shao¹, Xiaojun Chen¹, Chao Wang¹

Affiliation

¹ Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.

^# Contributed equally.

Abstract

Background: The molecular classification of endometrial cancer has previously been shown to be associated with clinical outcomes. However, there are insufficient data to support the routine use of molecular classification for the treatment of patients seeking fertility preservation.

Methods: Here, we retrospectively investigated 90 patients received fertility-sparing treatment. We used a next generation sequencing (NGS) panel to classify these patients into four subtypes. All patients received hormonal therapy combined with hysteroscopy. Therapeutic effects were evaluated by hysteroscopy every three months during the treatment.

Results: Patients with POLE mutations had the highest disease progression rate (50.0%, P=0.013), while the microsatellite instability-high (MSI-H) group had the highest recurrence rate (50.0%, P=0.042). PIK3CA mutation (hazard ratio (HR): 0.61; 95% confidence interval (CI): 0.37-0.99; P=0.046), overweight (HR: 0.56; 95% CI: 0.32-0.96; P=0.033) and obesity (HR: 0.44; 95% CI: 0.20-0.95; P=0.036) were associated with a significantly lower cumulative complete response (CR) rate. The combination of gonadotropin-releasing hormone analogues (GnRH-a) and letrozole (HR: 3.43; 95% CI: 1.81-6.52; P< 0.001) was associated with a significantly higher cumulative CR rate. KRAS mutation was significantly associated with disease progression (P=0.002). In wild-type TP53 patients, PTEN and PIK3CA mutations significantly prolonged the duration of treatment to achieve CR (log rank P=0.034; P=0.018).

Conclusion: The implementation of molecular classification for EC patients undergoing fertility-sparing treatment is promising and can facilitate the selection of appropriate medical regimes to achieve better outcomes in patients with EC who require fertility preservation treatment.

Keywords: NGS - next generation sequencing; endometrial cancer; fertility preservation treatment; molecular classifcation; molecular features.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. National Natural Science Foundation of China (General Program, 82273233), Natural Science Foundation of Shanghai (22ZR1408900), Clinical Research Plan of SHDC (No. SHDC2020CR4079), National Natural Science Foundation of China (General Program, 81772777), and Shanghai “Rising Stars of Medical Talent” Youth Development Program-Outstanding Youth Medical Talents (SHWJRS2021-99).