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Fertility-sparing approach in endometrioid grade II endometrial cancer: the role of molecular classification
Giorgio Bogani1, Luigi De Vitis2, Andrea Mariani3
1Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Department of Gynecologic Oncology, Milan, Italy.
Objective:
To investigate whether molecular classification could support individualized selection of patients with grade II endometrioid endometrial cancer for fertility-sparing approaches.
Methods:
This is a retrospective multi-institutional study. Data of patients undergoing fertility-sparing treatment with a levonorgestrel intrauterine device (with or without oral hormonal therapy) were retrieved. Surrogate molecular classification was used to categorize patients into 4 classes: (1) POLE-mutated, (2) mismatch repair deficient/microsatellite instability high, (3) p53 abnormal, and (4) no specific molecular profile.
Results:
Overall, data from 23 patients with grade II endometrioid endometrial cancer starting a fertility-sparing attempt were retrieved. The median patient age was 36 (range; 30-41) years. All patients underwent hysteroscopic-guided endometrial biopsies. Hysteroscopic resection of the tumor was performed in 9 (39.1%) patients. According to surrogate molecular classification, 1 (4.3%), 2 (8.7%), 3 (13.1%), and 17 (73.9%) patients were classified as POLE-mutated, p53 abnormal, mismatch repair deficient/microsatellite instability high, and no specific molecular profile, respectively. Molecular classification was not associated with 6-month response rates (p = .080) nor with best response rates (p = .366). Overall, 7 women attempted to achieve a pregnancy; 3 underwent in vitro fertilization. Three patients achieved a pregnancy (1 first-trimester miscarriage and 2 term live births). A total of 10 (43.4%) patients were diagnosed with progressive disease during hysteroscopic surveillance. Overall, 19 (82.6%) patients required hysterectomy. Three (13%) patients required adjuvant therapy for the presence of locally advanced disease (1 stage II, and 2 stage III). Over a median (range) follow-up of 28.7(8.2-91.1) months, no recurrence or disease-related death occurred.
Conclusions:
Less than 10% of women with grade II endometrioid endometrial cancer starting a fertility-sparing attempt achieve a term pregnancy. In our series, molecular classification did not influence response rate. Further collaborative registers are needed.
Insights
Fertility-sparing treatment for grade II endometrioid endometrial cancer yielded low pregnancy rates, with less than 10% achieving term birth. Molecular classification did not predict treatment response in this study.
Area of Science:
- Gynecologic Oncology
- Reproductive Medicine
- Molecular Pathology
Background:
- Endometrioid endometrial cancer (EEC) grade II presents treatment challenges, particularly for patients desiring fertility preservation.
- Fertility-sparing approaches (FSA) are considered, but their efficacy and patient selection require further investigation.
Purpose of the Study:
- To evaluate the utility of molecular classification in selecting patients with grade II EEC for FSA.
- To assess pregnancy outcomes and treatment response in patients undergoing FSA for grade II EEC.
Main Methods:
- Retrospective multi-institutional study of 23 patients with grade II EEC undergoing FSA using a levonorgestrel intrauterine device.
- Surrogate molecular classification categorized patients into POLE-mutated, mismatch repair deficient/microsatellite instability high, p53 abnormal, or no specific molecular profile groups.
- Outcomes assessed included response rates, pregnancy achievement, disease progression, and need for hysterectomy.
Main Results:
- Only 3 out of 7 women attempting pregnancy achieved live births (2 term), representing less than 10% of all patients.
- Molecular classification did not correlate with 6-month or best response rates (p = .080 and p = .366, respectively).
- High rates of disease progression (43.4%) and subsequent hysterectomy (82.6%) were observed.
Conclusions:
- Fertility-sparing treatment for grade II EEC results in low term pregnancy rates.
- Current molecular classification methods did not demonstrate predictive value for treatment response in this cohort.
- Further research through collaborative registries is essential to refine patient selection for FSA.
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