Original Article Int J Gynecol Cancer: first published as 10.1136/ijgc-2018-000036 on 7 January 2019. Downloaded from Pregnancy and oncologic outcomes after fertility-sparing management for early stage endometrioid endometrial cancer Su Hyun Chae,1 Seung-Hyuk Shim,1 Sun Joo Lee,1 Ji Young Lee,1 Soo-Nyung Kim,1 Soon-Beom Kang2 1Department of Obstetrics and HIGHLIGHTS Gynecology, Konkuk University • Pregnancy after fertility-sparing management can be successful. School of Medicine, Seoul, Korea • Grade 2 endometrial cancer might be a poor prognostic factor of fertility outcomes. 2Gynecologic Cancer Center, • Pregnancy itself slows the recurrence of endometrial cancer after complete remission. Department of Obstetrics and Gynecology, Konkuk University incidence has been gradually increasing in pre-men- Medical Center, Seoul, Korea ABSTRACT Objective Hormonal management is an alternative opausal women in recent years. Early detection is treatment for preserving fertility in patients with presumed possible because symptoms such as vaginal bleeding Correspondence to 1 3 6 7 Seung-Hyuk Shim, Department early stage endometrioid endometrial cancer. This study are common in early endometrial cancer. In this of Obstetrics and Gynecology, aimed to define the pregnancy and oncologic outcomes regard, fertility-sparing therapy in fertile women with Konkuk University School of and factors of successful conception after hormone early stage EC has recently been enforced.8 The gold Medicine, Seoul 05030, Korea; therapy for endometrioid endometrial cancer. standard EC management is hysterectomy and bilat- nastassja@ hanmail. net Methods We retrospectively analyzed patients presumed eral salpingo-oophorectomy with or without pelvic/ to have stage IA, grade 1–2 endometrioid endometrial para-aortic lymph node dissection.9 However, for Soon-Beom Kang, Gynecologic cancer who underwent fertility-sparing treatment. Cancer Center, Department Concurrent medroxyprogesterone and levonorgestrel- younger patients with early stage endometrioid EC of Obstetrics and Gynecology, release intra-uterine devices were used for treatment. who want to preserve fertility, this operation would Konkuk University Medical decrease their quality of life and remove any chance Center, Seoul, Korea; The pregnancy outcomes and oncologic outcomes were 20120097@ kuh. ac. kr compared between the pregnant and non-pregnant groups. of pregnancy. Results Seventy-one patients presumed to have stage IA, For these patients, fertility-sparing manage- grade 1–2 endometrioid endometrial cancer had complete ment with medroxyprogesterone acetate and levo- Received 24 June 2018 remission, and 49 of them tried to conceive. Twenty-two norgestrel-release intra-uterine devices has been http://ijgc.bmj.com/ Revised 5 September 2018 (44.9%) patients became pregnant; the total number of 10–16 Accepted 17 September 2018 recommended in several studies. Oral medroxy- pregnancies was 30. These pregnancies resulted in seven progesterone acetate use and levonorgestrel-release abortions (23.3%), one pre-term birth (3.3%), and 20 full- intra-uterine device insertion can prevent progres- term births (66.6%). The total live birth rate was 66.6 % sion of endometrial cancer and induce endometrial (20/30). The median duration of hormonal treatment was 17 11.9 months (range 4–49) and 12.0 months (range 3–35) regression. Patients were advised to try to conceive immediately after complete response following in the pregnant and non-pregnant groups, respectively. on September 27, 2021 by guest. Protected copyright. On multivariate analysis, age, body mass index, treatment medroxyprogesterone acetate treatment if pregnancy duration, medroxyprogesterone dose, and number of was desired. Although there have been some reports dilatation and curettage biopsies were not significantly of pregnancy outcomes in these patients, there has associated with pregnancy failure, but the association been little research into what factors are associated with grade (OR 6.2, 95% CI 1.0 to 38.9; P<0.05) was with successful pregnancies.18–21 The aim of this study statistically significant. The median disease-free survival was to define the pregnancy outcomes and factors duration was 26 months (range 20–38) and 12 months of successful conception after hormone therapy for (range 4–48) in the pregnant and non-pregnant groups, respectively (P<0.05, log-rank test). endometrioid endometrial cancer. Moreover, the Conclusions A lower grade might be a positive factor for oncologic outcomes were compared between the future pregnancy. Moreover, successful pregnancy might pregnant and non-pregnant groups. be a factor in preventing recurrence. © IGCS and ESGO 2019. No commercial re-use. See rights and permissions. Published by INTRODUCTION BMJ. Endometrial cancer is the most common gynecolog- METHODS 1 2 To cite: Chae SH, Shim S-H, ical cancer in the USA and Europe. Its incidence We retrospectively analyzed patients with presumed Lee SJ, et al. Int J Gynecol in Korea is rising gradually.3–5 Endometrial cancer stage IA, grade 1–2 endometrioid EC patients who Cancer 2019;29:77–85. is common in post-menopausal women, but its underwent fertility-sparing treatment between Chae SH, et al. Int J Gynecol Cancer 2019;29:77–85. doi:10.1136/ijgc-2018-000036 77 Original Article Int J Gynecol Cancer: first published as 10.1136/ijgc-2018-000036 on 7 January 2019. Downloaded from Figure 1 Outcome of patients with endometrial cancer after hormone treatment. January 2005 and December 2017. Our institutional review board Persistent disease was defined as no regression within 6 months approved this study (KUH1040065). from the initial treatment. Progressive disease was defined as a FIGO stage or grade upgrade that occurred during follow-up. Increasing Patients the medroxyprogesterone acetate dose to 1000 mg was considered Patients with endometrioid endometrial cancer were selected by if the patient had 6 to 9 months of persistent disease in follow-up pathologic confirmation with dilatation and curettage biopsy (D&C). D&Cs. Recurrence was diagnosed if carcinoma was observed on Our gynecologic oncology pathologist reviewed all pathology slides, pathology after complete remission.30 An anti-adhesive medication even those from outside hospitals. All patients underwent a full (poloxamer) was used in the endometrial cavity every time D&C workup, such as abdominal-pelvis CT, abdominal-pelvis with liver was performed.31 32 Treatment was stopped when two serial eval- coverage MRI, positron emission tomography-CTscan, mammog- uations revealed no evidence of carcinoma on pathology. Hormone http://ijgc.bmj.com/ raphy, cancer antigen (CA) 125, and other laboratory tests. After treatment and levonorgestrel-release intra-uterine device insertion workup, patients who were presumed to have stage IA endome- were terminated if a patient with complete remission wanted to trioid endometrial cancer with grade 1 or 2 were included. Myome- conceive. During fertility treatment or the conception trial period, trial invasion was evaluated with MRI. Combination of T2-weighted follow-up was scheduled every 3 months for a general gynecologic imaging with contrast-enhanced T1-weighted imaging including examination and transvaginal ultrasound. Endometrial pathology dynamic contrast-enhanced MR imaging can provide appropriate 22 was obtained if the patient had symptoms or abnormal examination on September 27, 2021 by guest. Protected copyright. information for the assessment of myometrial invasion. Endome- results. Surgery was recommended after childbearing or when the trial cancer was staged with the International Federation of Gyne- 23 patient did not want to get pregnant anymore. Patients with persis- cology and Obstetrics (FIGO) system. Hormonal therapy was used tent disease for more than 12 months, progressive disease, or for those who wanted to preserve fertility and had presumed stage recurrent disease were strongly recommended to undergo surgery. IA, grade 1 or 2 endometrioid endometrial cancer. Several studies are proposed to treat stage IA, grade 2 endometrioid endometrial cancer for fertility-sparing.24–27 Patients with non-endometrioid Statistical Analysis histology or presumed stage IA, grade 3 or over stage IB endome- The primary outcome was to compare the pregnant and non-preg- trial cancer with any grade were excluded. nant groups in terms of all possible factors that might be associ- ated with pregnancy success such as age, tumor grade, treatment Management and Follow-up duration, time of remission, progestin dose difference, number of Hormonal treatment was started with oral medroxyprogesterone D&Cs, and endometrial thickness on transvaginal ultrasound. The acetate 500 mg once daily. In addition, levonorgestrel-release secondary outcome was to compare the pregnancy and oncologic intra-uterine devices were inserted at the beginning of treatment. outcomes between the two groups. Depending on the normality of Follow-up for D&C was done every 3 months with transvaginal the distribution of continuous variables, the Student’s t-test or the ultrasound and CA-125 tests.28 29 Levonorgestrel-release intra- Mann-Whitney U test was used to compare the mean values of uterine devices were changed every 3 months after D&Cs. Complete the two groups. The χ2 test was used to compare the frequency remission was confirmed if carcinoma was absent on pathology. distribution of categorical variables. We performed univariate 78 Chae SH, et al. Int J Gynecol Cancer 2019;29:77–85. doi:10.1136/ijgc-2018-000036