Prognosis Analysis Of Fertility-sparing Treatment For Early-stage Endometrial Cancer And Highly Atypical Hyperplasia

BackgroundEndometrial cancer is one of the most common malignancies in female reproductive system. There is an increased tendency of patients to be diagnosed at a young age, and a majority of these young patients are nulliparous with a diagnosis of early-stage and highly differentiated endometroid endometrial cancer. The 5-year survival rate for them is above 90.0%. The standard treatment is total hysterectomy and bilateral salpingo-oophorectomy and surgical staging. However, this procedure leads to loss of fertility. Now, more and more clinicians try to utilize fertility-sparing treatment to give them a chance to have their own babies.Objectives1. To conduct a systematic review and meta-analysis of oral progestin treatment for early-stage endometrial cancer globally and evaluate its efficacy and safety.2. To set up fertility-sparing treatment for early-stage endometrial cancer and highly atypical hyperplasia database and analyze clinicopathological features.3. To compare the expression patterns of molecular markers of lipid metabolism in curettage slides along treatment procedure and explore the specific molecular markers that are related to efficacy and prognosis of fertility-sparing treatment.Methods1. We conducted a systematic review and meta-analysis of the proportions from observational studies. Original studies were selected if patients with early-stage endometrial cancer, especially those of reproductive age, were treated with oral progestin. We conducted searches on studies listed in MEDLINE, EMBASE and COCHRANE that were published through June 2014, and relevant articles were also searched. Results were obtained using random effects model.2. We searched the case database of Perking Union Medical College Hospital from 1994 to 2014, and patients fulfilling the criteria (pathological diagnosis of early-stage endometrial cancer or highly atypical hyperplasia by the pathologists of our hospital, patients of reproductive age and willing to accept fertility-sparing treatment) were picked up. We summarized the clinicopathological features and explore factors that might be related to prognosis.3. For every patient, slides from curettage at 6 different point of treatment procedure including pretreatment, during treatment, after treatment, relapse, during retreatment and after retreatment were obtained and immunohistochemistry was performed to investigate the expression patterns of APOD, LEPR, FASN, SCD1, SREBP1 and HOXA10 along treatment procedure and to explore their possible relevance to clinicopathological features and prognosis.Results1. In the meta-analysis, after oral progestin treatment, patients achieved a disease regression rate of 82.4%, a relapse rate of 25.0%, a pregnancy rate of 28.8% and a live birth rate of 19.6%. Body weight gain, liver dysfunction and abnormal blood coagulation test results were the most common treatment-related adverse effects. Only 2 disease-related death was reported during the follow-up duration.2. There existed large heterogeneity among included studies of the meta-analysis, but none of patients’age, patients’region, treatment and follow-up duration contributed to it.3. The complete regression rate of fertility-sparing treatment for initial treatment and retreatment in our hospital was 93.7% and 100.0% separately with a 5-year survival rate of 100.0%. The relapse rate was 33.7%, while the 1-year,3-year and 5-year progression-free survival rate was 89.9%,50.6% and 33.6%. Maximal body mass index changes during treatment and follow-up duration were the only two independent risk factors for relapse. None of the clinicopathological features was relevant to progression-free survival curve.4. Common adverse effects included body weight changes, abnormal platelet and blood coagulation test results, liver dysfunction and irregular vaginal bleeding. No thromboembolism was reported.26.7% of patients who took surgeries were found to have unilateral ovarian or pelvic floor metastasis. None of our patients died during the follow-up duration.5. Across the treatment procedure, the expression patterns of APOD, LEPR, FASN, SCD1 and SREBP1 in endometrial glands had no statistic significance, while those changes in endometrial stroma were statisticly significant. And expression patterns of HOXA10 in both endometrial glands and stroma also had statistic significance.6. Pretreatment expression of APOD, LEPR, FASN, SCD1 and SREBP1 was irrelevant to prognosis, while the expression of SREBP1 in endometrial stroma was positive correlated with treatment duration (correlation coefficient 0.307, P 0.041). And in slides after treatment, the expression of FASN and SREBP1 in complete regression group was higher than that in stable disease group with statistic significance.ConclusionsFertility-sparing treatment is feasible and safe for patients of reproductive age who are diagnosed of early-stage endometrial cancer and highly atypical hyperplasia. Molecular markers of lipid metabolism were not enough to predict the prognosis of fertility-sparing treatment. Lipid metabolism in stroma might be a future research direction.