Endometrial cancer and fertility

PURPOSE OF REVIEW: Endometrial cancer can affect reproductive-age women who may desire fertility preservation. This article discusses the current, available data about conservative management of endometrial cancer in young women. RECENT FINDINGS: Reproductive-age women with well differentiated endometrial carcinoma have an overall favorable prognosis provided that the tumor is identified at an early, noninvasive stage; however, advanced disease can be present. This article discusses current modalities to evaluate and clinically stage endometrial cancer including hysteroscopy, dilation and curettage, pelvic ultrasound, abdominopelvic computed tomography scan, pelvic magnetic resonance imaging, tumor marker CA125 level, and surgical exploration with laparoscopy or laparotomy. Thorough evaluation is critical as 10 to 29% of young women with endometrial cancer have a synchronous ovarian malignancy. Detailed counseling about the risks and benefits of conservative management, and expectations for fertility after treatment, surveillance, and definitive surgical management is essential. Multiple effective protocols exist for conservative treatment of endometrial cancer, and the initial response rates are as high as 57 to 75%. Successful pregnancies have occurred after conservative management, spontaneously, and with assisted reproductive technologies. SUMMARY: There are no standard recommendations for selection of appropriate women, treatment protocols, or long-term surveillance for conservative management of clinical stage I endometrial adenocarcinoma, and larger prospective clinical studies are warranted.     

Fertility-sparing management of endometrial adenocarcinoma

Approximately 15% of patients with endometrial cancer are premenopausal. Previous studies largely support the conservative treatment of endometrial cancer in women desiring future fertility. From these studies, 75% to 80% of patients demonstrate a complete response to progestin therapy and the average recurrence rate is 30% to 35%. Conservative therapy should be reserved for women with International Federation of Gynecology and Obstetrics grade I tumors. Before conservative management, patients should be informed of the elevated risk (11%-29%) of concurrent ovarian cancer in cases of premenopausal endometrial cancer, and screening and ongoing surveillance during the treatment period is mandatory. A suggestion of myometrial invasion or metastatic disease is a contraindication to conservative management. Individuals meeting criteria for Lynch syndrome testing should be referred to genetic counseling. Fertility treatment should be individualized, and close surveillance is required during treatment. Staging hysterectomy is recommended after the completion of the childbearing period. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After participating in this activity, physicians should be better able to select appropriate candidates with endometrial cancer for fertility-sparing treatment. Educate patients with endometrial cancer regarding the risks and benefits of standard of care therapy and conservative therapy and screen appropriate patients for Lynch syndrome.     

Updates on Conservative Management of Endometrial Cancer

Endometrial cancer is the most common gynecologic cancer in the United States. It is typically diagnosed in postmenopausal women. However, given the increasing incidence of risk factors such as obesity and diabetes in younger women, it is becoming a more prevalent problem in this age group. When endometrial cancer is diagnosed in patients of reproductive age, the standard surgical option of hysterectomy and bilateral salpingo-oophorectomy may not be ideal for women interested in future fertility. Hence, conservative options for select patients should be discussed along with the associated outcomes of each approach. A number of studies have shown that in patients with complex atypical endometrial hyperplasia and grade I endometrial carcinoma, a conservative approach is safe and feasible. The aim of this review is to summarize published evidence of fertility-sparing options such as hormonal therapy, hysteroscopic resection of focal lesions, and the role of intrauterine devices. We will also provide the latest updates on ongoing prospective trials that explore strategies for conservative management in women with medical comorbidities or those interested in fertility preservation.     

年轻早期高分化子宫内膜样腺癌患者保守治疗新进展

子宫内膜癌（EC）是常见的妇科恶性肿瘤,对年轻未生育的早期高分化子宫内膜样腺癌患者来说,保守治疗显得尤为重要。传统保守治疗药物包括孕激素、促性腺激素释放激素类似物（GnRHa）和芳香化酶抑制剂（AIs）等。宫腔镜电切术联合孕激素治疗是年轻子宫内膜样腺癌患者保留生育功能的新型治疗方式,在缓解率、妊娠率、不良反应发生率和复发率等方面优于传统保守治疗,但目前关于手术操作及术后激素治疗尚无统一标准。肥胖EC患者应治疗肥胖以降低复发风险,其中以减重手术效果最为显著、持久。现已证实减重手术对体质量指数（BMI）≥35 kg/m2的早期高分化子宫内膜样腺癌患者是有效干预。建议BMI≥35 kg/m2或BMI≥30 kg/m2且合并代谢综合征/2型糖尿病的年轻早期高分化子宫内膜癌患者,若经非手术治疗肥胖疗效不佳,可考虑以减重手术作为辅助治疗     

Preserving fertility before assisted reproduction in women with endometrial carcinoma: case report and literature review

Fertility-preserving treatment with progestin may be considered in nulliparous women with well-differentiated endometrial carcinoma. Recently, assisted reproductive treatments have been performed to achieve a rapid pregnancy in such cases. This report evaluates a 39-year-old woman who admitted with menorrhagia and primary infertility. Owing to persistent menstrual irregularity and thick endometrium, a diagnostic office hysteroscopy with endometrial biopsy was performed and revealed a well-differentiated adenocarcinoma. Although the woman wished to retain her childbearing potential with conservative management followed by an assisted reproduction cycle, the repeated endometrial biopsies during progestin treatment revealed persistent adenocarcinoma. Complementary surgery was performed due to persistent endometrial malignancy, which noted well-differentiated endometrioid adenocarcinoma without myometrial invasion or extrauterine disease. A review of cases with endometrial carcinoma that have been treated with conservative management and a subsequent assisted cycle is also presented here. To date, there are 14 such reports, including 15 women and 21 healthy infants. However, obtaining remission and maintaining the reproductive capability may not always be possible, even in early-stage cases. Therefore, patient and physician should always consider carefully if fertility-preserving management is preferred after diagnosis of endometrial carcinoma.     

Clinicopathologic study of uterine endometrial carcinoma in young women aged 40 years and younger

To clarify what constitutes the adequate management of uterine endometrial carcinoma in young women, we reviewed clinicopathologically 31 patients aged 40 years and younger between January 1991 and June 2004. As a primary treatment, 12 cases chose hormonal treatment with medroxyprogesterone acetate (MPA; 600 mg/day) due to no findings of myometrial invasion and diagnosis of a grade 1, well-differentiated adenocarcinoma. In remaining 19 cases, surgery was performed. All the 19 patients who received surgery as a primary treatment are alive, with no evidence of a recurrence of the disease. In the 12 patients who received hormonal treatment, 8 patients eventually received a hysterectomy because of recurrence or no response to MPA. Of these eight patients, myometrial invasion was recognized in three patients. One of the eight patients died of the metastasized disease to the liver and brain after hysterectomy. After hormonal treatment, 4 of the 12 patients were exempted from surgery and showed no evidence of recurrence. Two patients had viable children. Progesterone receptor was negative in one case that died. Careful consideration should be given to hormonal treatment with MPA for the conservative management of endometrial carcinoma in young women. Moreover, MPA is not always a consistent management for every patient.     

Carcinoma of the endometrium treated only by vaginal route

The gold standard treatment for endometrial cancer is surgery. Less invasive surgical procedures (e.g. vaginal surgery), provide equivalent cure rates and are preferred interventions for elderly women or women with significant co-morbidities with endometrial cancer stage I. A commonly referred limitation of vaginal surgery in endometrial carcinoma is the difficulty of carrying out lymphadenectomy when necessary. However, women elected for vaginal procedures are those who should not need lymphadenectomy because they are at low risk for lymph-node metastasis, and can therefore be treated by less invasive surgery with similar oncology outcomes to those women treated with abdominal surgery. Vaginal hysterectomy, therefore, has a definite place in the therapeutic armamentarium of the gynaecological oncologist. Although it is not recommend routinely or indiscriminately, its use adds flexibility to the management of selected women with stage I?endometrial carcinoma, without affecting their oncologic outcomes.     

Fertility preservation in gynecologic cancer

SUBJECT: Management of patients with gynecologic cancer can now often be tailored to the extent of the disease and preservation of child-bearing ability and/or sexual function may be possible for certain women with early invasive disease. METHOD: A better understanding of the tumor-biology, and the consideration of different clinicopathologic factors, that bear prognostic significance in therapeutic modalities, will allow more and more individualization of treatment. DISCUSSION: Management of young women with early gynecologic cancer should therefore be individualized with the risk of conservative therapy balanced against the dangers and advantages of more radical therapy. Experts in gynecologic oncology and infertility together with an informed patient and her family should make treatment decisions. OUTCOME: This article will review the conservative surgical management of early invasive cancers of the ovary, cervix and endometrium, in order to help preserve child-bearing capacity. In addition, management of gynecologic cancers diagnosed during pregnancy will also be discussed.     

Advanced endometrial cancer with serous metastasis in a 17-year-old

BACKGROUND: Endometrial cancers with a component of serous histology generally occur in postmenopausal women and can present with advanced disease even in the absence of a deeply myoinvasive primary malignancy. We present a case of stage IIIC endometrial cancer with serous histology in a 17-year-old. CASE: A 17-year-old presented with menorrhagia requiring blood transfusion and a transvaginal ultrasound demonstrated a 31 mm endometrial stripe within a bulky uterus. Endometrial curettage revealed a grade 2 endometrioid adenocarcinoma. The patient desired definitive surgical management for her disease; a stage IIIC endometrial cancer with focal low-grade serous carcinoma among a grade 2 endometrioid carcinoma was noted to be superficially myoinvasive. Multiple pelvic lymph nodes had evidence of metastatic serous adenocarcinoma. Platinum-based chemotherapy was administered, and the patient is without disease 24 months following therapy. CONCLUSION: Advanced endometrial cancer with metastasis of serous carcinoma to the retroperitoneal lymph nodes can occur, albeit extraordinarily rarely, in very young women. This information is critically important when counseling a woman regarding conservative management of endometrial adenocarcinoma with the interest of preservation of her fertility.     

Clinical aspects of uterine papillary serous carcinoma

PURPOSE OF REVIEW: We review the demographic and clinicopathologic characteristics, and prognosis of women diagnosed with uterine papillary serous carcinoma, with a focus on clinical management. RECENT FINDINGS: Pathologic evaluation of postmenopausal bleeding is preferred for patients who fit the profile of a high-risk endometrial cancer such as uterine papillary serous carcinoma. Women diagnosed with endometrial cancer who fit this profile and all women with uterine papillary serous carcinoma should undergo comprehensive surgical staging and aggressive cytoreduction of extrauterine disease. Adjuvant therapy remains controversial. Several recent investigations reported on the potential benefit of adjuvant chemotherapy, with many recommending additional loco-regional radiation. SUMMARY: Despite the lack of randomized trials on uterine papillary serous carcinoma, several recent reports have provided insight into the diagnosis, surgical management, and adjuvant treatment of this high-risk endometrial cancer.     

A rare case of choroidal metastasis presented after conservative management of endometrial cancer

Hematogenous dissemination from endometrial cancer is quite rare. We report a 31-year-old woman who developed choroidal metastasis following conservative management of early-stage endometrial carcinoma. She had received kidney transplantation and was taking steroids and cyclosporine. Three years after hysterectomy for persistent endometrial carcinoma, she developed multiple metastatic disease (to both lungs and right pelvis), and while on treatment with paclitaxel and carboplatin, she complained of a rapid visual deterioration. Ophthalmologic evaluation revealed a metastatic choroidal tumor associated with multiple central nervous system metastases. The patient refused further treatment and died 1 month after diagnosis of choroidal involvement. In conclusion, this is the first reported case of choroidal metastasis from endometrial cancer and highlights the need to consider immunosuppressive treatment as an absolute contraindication to conservative fertility-sparing treatment in gynecological malignancies.     

年轻子宫内膜癌女性保留生育及卵巢功能的治疗进展

子宫内膜癌（endometrial carcinoma,EC）是女性生殖系统三大恶性肿瘤之一,年轻育龄期EC患者相对少见,但随着子宫内膜癌发病率的逐渐上升,以及现代生活习惯的改变,EC出现明显年轻化趋势。EC的标准治疗方案使得女性永久性失去生育功能以及绝经前女性提前进入更年期,严重影响年轻患者的生活质量。故年轻EC患者保留生育功能或保留卵巢功能的治疗方案逐渐受到重视。现有的保留生育功能方案主要有：孕激素、芳香化酶抑制剂、二甲双胍等药物治疗以及宫腔镜下EC病灶切除术。多项研究已经证实,肥胖与EC发生发展相关,保留生育功能治疗期间体质量管理同样也至关重要。现就年轻EC女性保留生育及卵巢功能治疗以及治疗期间体质量管理等的研究进展进行综述。     

Hormone therapy for younger patients with endometrial cancer

The relationship between hormones and endometrial cancer is well known because disease states, such as chronic anovulation and endogenous estrogen production from hormone-secreting tumors (for example, granulosa cell tumor of the ovary), are related to excess estrogen, and unopposed estrogen use might lead to endometrial overgrowth, hyperplasia, and subsequent development of endometrial carcinoma. Therefore, the possibility of using antihormone therapy in endometrial carcinoma and/or its precancer lesions, such as simple hyperplasia with and without atypia and complex hyperplasia with and without atypia, is always supposed, as in the management of breast cancer. In addition, if women in whom endometrial cancer is diagnosed are very young, some critical issues should be considered, including the possibility of ovary preservation-partial preservation of fertility and the possibility of both ovary and uterus preservation-complete preservation of fertility. Other factors are also important to consider and include oncologic risk, appropriateness of candidates for treatment, type of hormone use, response rate of hormonal therapy, appropriate surveillance, and additional counseling for issues such as anxiety about relapse and metastasis, distress about side effects, advice of the family, advice of the medical staff, and economic burden.This review will be focused on updated information and recent knowledge of the use of hormones in the management of younger women with endometrial cancer who want fertility preservation.     

A successful live birth with in vitro fertilization and thawed embryo transfer after conservative treatment of recurrent endometrial cancer

Estrogen-dependent early stage endometrial cancer is relatively common in young women of reproductive age. The standard treatment is hysterectomy and bilateral salpingo-oophorectomy (BSO), even in early stage well-differentiated endometrial cancer patients. This surgical option results in permanent loss of fertility. There have been some reports of live births using in vitro fertilization after conservative management of endometrial cancer with high-dose progestin for the purpose of fertility preservation. However, most were not recurrent cases and pregnancy was achieved through conventional in vitro fertilization, which usually raises serum estradiol levels and may lead to the recurrence of endometrial cancer. To date, it is hard to find a case that can be referred for any possible different approach needed for the patients who experience recurrence. Here we report a successful live birth with in vitro fertilization using letrozole to maintain physiological levels of estradiol, and subsequent thawed embryo transfer after elective cryopreservation of embryos in a patient with recurrent endometrial cancer. There has been no evidence of disease recurrence at one year after delivery.     

ACOG committee opinion. No. 336: Tamoxifen and uterine cancer

Tamoxifen may be associated with endometrial proliferation, hyperplasia, polyp formation, invasive carcinoma, and uterine sarcoma. Any symptoms of endometrial hyperplasia or cancer reported by a postmenopausal woman taking tamoxifen should be evaluated. Premenopausal women treated with tamoxifen have no known increased risk of uterine cancer and as such require no additional monitoring beyond routine gynecologic care. If a typical endometrial hyperplasia develops, appropriate gynecologic management should be instituted, and the use of tamoxifen should be reassessed.     

Coexisting ovarian malignancy in young women with endometrial cancer

OBJECTIVE: In premenopausal women with endometrial cancer, ovarian preservation may be a consideration. Our objective was to examine the occurrence of coexisting ovarian malignancy and to identify predictors of adnexal involvement. METHODS: With institutional review board approval, a retrospective chart review was conducted of young women with endometrial cancer identified at 4 affiliated institutions from 1996 to 2004. RESULTS: Among 102 young women (aged 24-45 years) who underwent hysterectomy for endometrial cancer, 26 (25%) were found to have coexisting epithelial ovarian tumors: 23 were classified as synchronous primaries, and 3 as metastases. Ovarian cancer histology was endometrioid in 92% of cases. Among the 26 cases of coexisting ovarian involvement, 12 (46%) had grade 1 endometrial cancer on preoperative biopsy, 4 (15%) had normal preoperative imaging of the adnexa, and 4 (15%) had benign-appearing ovaries at the time of intraoperative assessment. On final pathology, 18 of 26 cases (69%) occurred in patients with grade 1 endometrial cancers, and 15 (58%) occurred with inner myometrial invasion. Our study further highlights the risk of conservative management with 1 case of ovarian cancer diagnosed 9 months after hysterectomy with ovarian conservation for a stage IA, grade 1 endometrial cancer and a case of advanced endometrial cancer metastatic to the ovaries developing 3 years after successful resolution of a grade 1 endometrial cancer treated with megestrol acetate (Megace). CONCLUSION: Careful preoperative and intraoperative assessment of the adnexa is mandatory in young women with endometrial cancer. Those who desire ovarian preservation should be counseled regarding the high rate of coexisting ovarian malignancy.     

Neoadjuvant chemotherapy plus fertility-sparing surgery in locally advanced cervical cancer: case report

Cervical carcinoma is the second most common malignant disease worldwide, often occurring in young women who have not completed childbearing. In this era of emphasis on conservative treatments, management of cervical cancer could be influenced by patient desire to preserve fertility, maintaining the uterine corpus. Herein is reported the case of a young woman with locally advanced cervical cancer that was successfully treated using neoadjuvant chemotherapy followed by simple vaginal trachelectomy and laparoscopic lymphadenectomy. The success of such an approach, which is not the standard of care in this disease, suggests that additional studies should be performed in a selected population.     

Patients' preferences in the evaluation of postmenopausal bleeding

Objective  To assess patients' preferences for diagnostic management of postmenopausal bleeding (PMB).
Design  A structured interview.
Setting  A teaching hospital with office hysteroscopy facilities.
Population  Thirty-nine women with PMB and with a completed work-up including an office hysteroscopy.
Methods  A structured interview was taken from 39 women who had had an office hysteroscopy in the diagnostic work-up for PMB. Women were informed about the probability of endometrial carcinoma versus benign disease and about advantages and disadvantages of different diagnostic strategies, i.e. expectant management after ultrasound or complete diagnostic work-up, including invasive procedures.
Main outcome measures  Women were informed about the probability of endometrial carcinoma versus benign disease and about advantages and disadvantages of different diagnostic strategies, i.e., expectant management after ultrasound or complete diagnostic work-up including invasive procedures. Women were asked to make a trade-off between different options.
Results  Most women wanted to be 100% certain that carcinoma could be ruled out. Only 5% of the women were willing to accept more than 5% risk of false reassurance. If the risk of recurrent bleeding due to benign disease exceeded 25%, the majority of women would prefer immediate diagnosis and treatment of benign lesions.
Conclusion  Women with PMB are prepared to undergo hysteroscopy to rule out any risk on cancer. This finding implicates that the measurement of endometrial thickness with transvaginal ultrasound as a first-line test in the assessment of PMB should be reconsidered.     

Successful conservative treatment of endometrial carcinoma permitting subsequent pregnancy: report of two cases

Two women with endometrial carcinoma who wished to preserve their childbearing ability received conservative treatment by medroxyprogesterone acetate (MPA, 600 mg/day for 22 weeks and 29 weeks, respectively). Following regression of endometrial lesions, their infertility was treated by inducing ovulation. Intact pregnancy was diagnosed 13 months and 11 months after completion of the MPA treatment, respectively. One patient had a twin pregnancy and delivered two infants at 35 weeks of gestational age. The other patient delivered a full-term baby. They had no evidence of recurrence 60 months and 31 months after the conservative treatment, respectively. We believe this conservative treatment with progestin may be safely performed for young patients with endometrial cancer who wish to preserve their fertility.     

Young patients with endometrial carcinoma selected for conservative treatment: a need for vigilance for synchronous ovarian carcinomas, case report and literature review

BACKGROUND: The aim of this paper is to report a case of synchronous ovarian malignancy in a very young patient with early endometrial cancer who desired fertility-sparing management. CASE: Twenty one-year-old patient presented with an apparent early stage endometrial cancer and desiring conservative management. After failure of conservative management for 3 years, surgery was performed. An incidentally small papillary serous ovarian tumor of low malignant potential was found. CONCLUSION: Careful preoperative and intraoperative assessment of the adnexa is mandatory in young women with endometrial cancer. Those who desire ovarian preservation should be counseled regarding the high potential for coexisting ovarian malignancy.