| Background and Objectives:Endometrial cancer is the most common gynecologic malignancy and affects predominantly postmenopausal and menopausal women.Globally,the incidence of endometrial cancer appears to be rising and the number of young patients are tending to increase. Approximately 14% of women diagnosed with endometrial cancer are younger than 40 years of age,and about 80% of these women are nulliparous.Therefore,fertility-sparing treatments have become more desirable in recent years. Endometrial cancer can be diagnosed early because of its early clinical symptoms.The prognosis is relatively good and most cases are sensitive to hormone therapy. So young patient in early stage can consider hormone therapy for fertility sparing.Fertility sparing in endometrial cancer currently lack randomized controlled clinical trials of large sample. The 2012 NCCN guidelines mentioned about the fertility-sparing therapy in young patient with endometrial cancer for the first time.Until 2016 NCCN guideline also,the clear treatment process about the dosage,treatment time, the molecular marker to predict the theraputic effect of progesterone in young patient with endometrial cancer is not given.We conducted a prospective study in 36 patients using large dose of oral progesterone combined with metformin, tamoxifen and hysteroscopic endometrial resectioning in early stage of endometrial cancer and atypical endometrial hyperplasia.The 36 patients met the inclusion criteria from Tianjin central Obstetric and Gynecology Hospital we included, the investigation and analysis, summarized the clinical date, analized the treatment effect, pregnancy outcome, survival outcome and related effects. The purpose of this study is to determine the efficacy and safety of the fertility sparing treatment to the young patient with endomentrial cancer and atypical endometrial hyperplasia to improve the pregnancy rate and to provide relevant reference index.Subjects and methods:The inclusion criteria are: (1) the age younger than 40 years who are highlymotivated to maintain their reproductive protential; (2) histologically proved grade 1 endometrial carcinoma or atypical endometrial hyperplasia; (3) no evidence of myometrial invasion or extrauterine extension or cervical invasion after evaluation by pelvic ultrasonography and / or magnetic resonance imaging( MRI);(4) presence of progesterone receptor(PR); (5) normal serum levels of CA125(<35U/ml); (6) without contraindications for hormone treatment;(7) convenient for close follow-up;(8)patients'understanding and acceptance that the treatment is not the standard treatment for their disease.Methods: 17 patients with endometrial cancer and 19 patients with atypical endometrial hyperplasia enrolled into this study received hysteroscopy with curettage before the therapy and were confirmed in decrease in tumor cells. From the 5th day of menstruation MA 160mg was given orally per day for 21 days for three months cycle.All patients were followed up by hysteroscopic resection and endometrial curettage at interval of 3 months. The patients who did not have menstruation for 2 weeks after withdraw of MA 160mg of 21 cycle, they were given MA160mg for next 60 days. If the immunohistochemistry of progesterone recepter(PR) is less than 50%, oral tamoxifen 20mg per day is given. The patient with diabetes or insulin resistance then tablet metformin 750mg per day is given. If any lesions seen in pelvic ultrasonography or MRI, hysteroscopic resection of endometrial lesion was done and the oral treatment of MA 160mg was continued. After 3 cycles of treatment all patients were examined by hysteroscopy and currettage of endometrial tissue was done. The endometrial tissue was sent for histopathology examination. After complete remission of endometrial carcinoma or atypical endometrial hyperplasia was achieved ,patients used assisted reproductive technology.Results : The total number of patients involved were 36, among them 17 patients had grade 1 endometrial carcinoma and 19 patients had atypical endometrial hyperplasia. Out of them, 31 patients (86. 1 %) achieved complete remission and 2(5.6%) got part remission, while 2 (5.6%) got stable disease and 1 (2.8%) got progressive disease.The mean duration to achieve complete remission was 8.26+0.87 months. One (2.8 %) interrupted the therapy because of the severe adverse effects. 6 experienced recurrence (19.4%) and 32 patients were free of disease at follow-up of 26.17±2.60 months, 4 patients were alive with disease.25 patients achieved complete remission and attempted pregnancy. Out of them, 9 patients (36%) achieved 11 pregnancies and 4 patients successfully delivered healthy baby. The interval between the completion of progestin therapy and conception was 7.33±0.83 months. The pregnancy rate of patients with atypical endometrial hyperplasia was 50% and of endometrial carcinoma was 18.2%. The pregnancy rate after Assisted reproductive technology was 100%,which is significantly higher than in those without assisted reproductive technology.Conclusions:This study about the fertility sparing treatment using high dose of oral progesterone combined with metformin, tamoxifen and hysteroscopic endometrial resection for conservation of fertility in young patient in early stage of endometrial carcinoma and atypical endometrial hyperplasia is rarely reported in China or abroad.In our study, a satisfactory rate of remission along with good outcome in pregnancy rate were obtained. Among 36 patients achieved 86.1% of complete remission and 36.1% of pregnancy, 19.4% of recurrence was the outcome. 32 patients survied without the disease and 4 patients survied with disease undergoing the hormone therapy during the study time. |
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