Conservative Management Of Endometrial Cancer Research Articles

Conservative management of early-stage endometrial cancer for fertility preservation: a survey study among Swedish gynecologists and gynecological oncologists

Conservative management of endometrial cancer (CMEC) is viable for women with early-stage disease wishing to preserve fertility, but there is poor knowledge regarding clinicians’ attitudes towards treatment or guidelines adherence. This 55-item survey study investigated CMEC-related experience, practice and attitudes among clinically active Swedish gynecologists and gynecological oncologists, focusing on reproductive eligibility criteria. The survey consisted of a general and two specific subsets, selectively delivered to clinicians active in infertility (subset A) and endometrial cancer (subset B) care. Answers from 218 clinicians were included. More than half agreed on CMEC whereas only 5% explicitly disagreed. The majority supported a fertility work-up to substantiate reasonable chances to pregnancy and live birth. Most disagreed about CMEC in case of previous unsuccessful fertility treatments, while more than 1/3 disagreed about CMEC in known fertility problems, recurrent miscarriages or previous children. Over 50% of respondents in subset A (n = 107) found it applicable with fertility investigations such as ovarian reserve testing or, in case of male partner, semen analysis. Respondents in subset B (n = 165) agreed on items based on existing recommendations regarding the oncological management of CMEC, including the use of continuous progestins, hysteroscopic resection of macroscopic lesions, control biopsy with curettage or hysteroscopy after 6 months of treatment, pursuing pregnancy as soon as possible after complete response, and performing a hysterectomy once live birth is achieved. While many clinicians were familiar with CMEC, the overall experience is limited. Fertility specialists seem less involved than oncologists in patient care but there is broad support for fertility-related eligibility criteria.

Chances of pregnancy and live birth among women undergoing conservative management of early-stage endometrial cancer: a systematic review and meta-analysis.

BACKGROUNDEndometrial cancer is common and usually occurs after menopause, but the number of women diagnosed during reproductive age is increasing. The standard treatment including hysterectomy is effective but causes absolute uterine factor infertility. In order to avoid or postpone surgery, conservative management of endometrial cancer (CMEC) has been proposed for younger women who want to retain their fertility.OBJECTIVE AND RATIONALEThe main objective of this study was to estimate the chances of pregnancy and live birth for women with early-stage endometrial cancer (EEC) who are managed conservatively for fertility preservation.SEARCH METHODSThe PRISMA recommendations for systematic reviews and meta-analyses were followed. Structured searches were performed in PubMed, Embase and the Cochrane Library, from inception until 13 June 2021. Inclusion was based on the following criteria: group or subgroup of women with Clinical Stage IA, well-differentiated, endometrioid endometrial cancer (from now on, EEC); CMEC for fertility preservation; and reported frequencies of women achieving pregnancy and/or live birth after CMEC. The following exclusion criteria applied: impossibility to isolate/extract outcome data of interest; second-line CMEC for persistent/recurrent disease; CMEC in the presence of synchronous tumours; case reports; non-original or duplicated data; and articles not in English. Qualitative synthesis was performed by means of tabulation and narrative review of the study characteristics. Study quality was assessed with an ad hoc instrument and several moderator and sensitivity analyses were performed.OUTCOMESOut of 1275 unique records, 133 were assessed in full-text and 46 studies were included in the review. Data from 861 women with EEC undergoing CMEC were available. Progestin-based treatment was reported in all but three studies (93.5%; 836 women). Complete response to treatment was achieved in 79.7% of women, with 35.3% of them having a disease recurrence during follow-up. Of 286 pregnancies obtained after CMEC; 69.4% led to live birth (9% of them multiple births) and 66.7% were achieved through fertility treatment. Based on random-effects meta-analyses, women treated with progestin-based CMEC have a 26.7% chance of achieving pregnancy (95% CI 21.3–32.3; I2 = 53.7%; 42 studies, 826 women) and a 20.5% chance to achieve a live birth (95% CI 15.7–25.8; I2 = 40.2%; 39 studies, 650 women). Sample size, average age, publication year, study design and quality score were not associated with the outcomes of progestin-based CMEC in moderator analyses with meta-regression. However, mean follow-up length (in months) was positively associated with the chances of pregnancy (regression coefficient [B] = 0.003; 95% CI 0.001–0.005; P = 0.006) and live birth (B = 0.005; 95% CI 0.003–0.007; P < 0.001). In sensitivity analyses, the highest chances of live birth were estimated in subsets of studies including only women of age 35 or younger (30.7%), the combination of progestins with hysteroscopic resection (30.7%), or at least 3 years of follow-up (42.4%).WIDER IMPLICATIONSProgestin-based CMEC is viable for women with well-differentiated, Clinical Stage 1A, endometrioid endometrial cancer who want to preserve their fertility, but there is room for improvement as only one-fifth of them are estimated to achieve live birth according to this meta-analysis. Further investigations on prognosis-driven selection, hysteroscopic resection and long-term surveillance are arguably needed to improve the reproductive outcomes of CMEC.

Lymph node metastasis probability in young patients eligible for conservative management of endometrial cancer

ObjectiveEndometrial cancer (EC) is a rare condition in young women. The objective of this study was to evaluate the risk of pelvic lymph node (LN) metastasis in young women with EC who are candidates for conservative management. MethodsUsing the SEER database, a population-based analysis was conducted to identify women <45 years with grade 1, 2, or 3 endometrioid adenocarcinoma stage IA (FIGO 2009) who underwent pelvic lymphadenectomy with at least ten LNs removed. The LN macrometastases rate based on conventional histological diagnosis was analyzed according to tumor grade and myometrial invasion (MI) on final histology. ResultsA cohort of 1284 women was analyzed. The LN metastasis rates were: 2/414 (0.5%) grade 1 EC without MI, 5/239 (2.1%) grade 2 or 3 EC without MI, 5/308 (1.6%) grade 1 EC with MI, and 14/323 (4.3%) grade 2 or 3 EC with MI. Tumor size was not correlated with LN metastasis probability. ConclusionsYoung patients eligible for conservative management have a low rate of LN macrometastasis, especially in stage IA without MI grade 1 EC. A systematic lymphadenectomy should not be performed in these patients. Prospective study evaluating the sentinel LN mapping in conservative management of EC could be performed to assess the LN micrometastasis rate.

Long-term fertility-sparing, conservative management of endometrial cancer with progestin, a case report and review of literature

Long-term fertility-sparing, conservative management of endometrial cancer with progestin, a case report and review of literature

Conservative management of endometrial cancer: a survey amongst European clinicians.

To investigate differences and similarities in the clinical approach of young clinicians managing women with endometrial cancer (EC) conservatively. A web-based survey was carried out. A platform of the European Network of Young Gynaecological Oncologists (ENYGO) database was used. A 38-item multiple-choice questionnaire was used to evaluate current practice in fertility-sparing management of EC. The survey covered investigations, treatment options, follow-up and management of recurrence and future family planning. Descriptive statistics were used. Overall, 116 out of 650 (17.84%) ENYGO members responded to the survey. In 92 (79.3%) centres, the caseload of early stage EC treated conservatively was less than 10 per year. One hundred and seven responders (93.8%) believe that treatment with progestins could be offered in grade 1 EC without myometrial invasion, but a minority would recommend it even for grade 2 tumours with no myometrial invasion or grade 1 with superficial invasion. The diagnostic tool for establishing grade of tumour was hysteroscopy with dilatation and curettage in 64 (55%) centres. Medroxyprogesterone acetate represents the most commonly prescribed progestogen (55, 47.4%). In 78 (67.2%) centres, a repeat endometrial biopsy was offered after 3months of treatment commencement. Recurrences are treated mostly with hysterectomy (81, 69.9%) with only a small number of responders recommending to repeat progestin treatment. Lynch syndrome is a contraindication for conservative management in half of the responders (57, 49.1%). Most clinicians agree that patients should be referred promptly for assisted reproductive techniques once complete response has been achieved (68, 58.6%). Our study shows that conservative management is increasingly offered to women affected by early stage EC wishing to preserve their fertility. Further studies and joint registries are required to evaluate safety and effectiveness of this approach in this probably growing number of patients.

Updates on Conservative Management of Endometrial Cancer

(Abstracted from J Minim Invasive Gynecol 2017; http://dx.doi.org/doi: 10.1016/j.jmig.2017.07.022) The aim of this article was to review current data from the literature on conservative management of endometrial cancer (EC). The authors provide the latest updates on ongoing prospective trials exploring strategies in women with medical comorbidities or those of reproductive age who want to preserve futility.

Poor Outcomes After Conservative Management for Low-Grade, Apparent Early-Stage Endometrial Cancer [334

INTRODUCTION: The conservative (fertility preserving) management of low-grade, early-stage endometrial cancer is gaining popularity. Some concerns could be raised in view of the tendency to underreport poor outcomes such as death, progression to advanced stage, or higher grade disease. METHODS: We reviewed published poor outcomes of low-grade, early-stage endometrial cancer and present two women who desired conservative management for fertility-preserving purposes and sustained poor outcomes in one tertiary care facility over a 5-year period. RESULTS: Despite established conservative management, the first patient's low-grade, early-stage endometrial cancer concealed an underlying pathology of clear cell adenocarcinoma. In the second case, a patient with low-grade endometrial cancer refused hysterectomy to attain fertility and when she accepted, was found to have stage IIIC1 (International Federation of Gynecology and Obstetrics 2009) disease. IMPLICATION: These cases indicate that conservative management of endometrial cancer should still be considered with caution, performed by experienced teams, and the potential risks be explained to the patients.

Conservative treatment of early endometrial cancer

Endometrial cancer is the most common cancer of the female genital tract in Europe and in the United States. Endometrial cancer has increased 21% in incidence since 2008, and the death rate has increased more than 100% over the past two decades. Approximately 15% of patients with endometrial cancer are pre-menopausal. The aim of this review is to discuss the conservative management of endometrial cancer. A number of studies largely support the conservative treatment of endometrial carcinoma (EC) in women desiring future fertility. We focus on the role of progestin hormonal therapy, including the risks associated with non-standard care, appropriate candidate selection, expected outcomes, various progestin agents and recommended follow-up.

Fertility-sparing treatment of endometrial cancer: options, outcomes and pitfalls

Endometrial cancer is the most common gynecologic malignancy in the United States, with over 40,000 cases diagnosed each year. While a majority of cases are diagnosed in post-menopausal women, up to 14% of cases will be in pre-menopausal women, including 4% diagnosed in women less than 40 years of age. While hysterectomy with bilateral salpingo-oophorectomy with assessment of the retroperitoneal lymph nodes is standard initial treatment for endometrial cancer, younger women may desire fertility sparing options. The decision to proceed with conservative management in this younger patient population is associated with multiple complexities, including the inherent oncologic risks of an inadequately staged and treated endometrial cancer, the risk of a synchronous or meta-synchronous cancer, the increased risk of an inherited genetic predisposition to malignancy and the lack of uniformity in the medical management and surveillance. In this review we will discuss the conservative management of endometrial cancer, specifically the role of progestin hormonal therapy, including the risks associated with non-standard care, appropriate candidate selection and work up, expected outcomes, various progestin agents and recommended follow-up.

10th International Conference of ACOS, June 13-15 2012

10th International Conference of the Asian Clinical Oncology Society (ACOS) was held in conjunction with 38th Annual Meeting of the Korean Cancer Association during the period of June 13-15, 2012 in COEX, which is the flagship conference facility of Korea located in the city of Seoul. Four sessions were allocated for gynecologic oncology in total. Four special lectures, four educational lectures, six oral presentations, and twenty-two poster presentations were delivered. The theme of educational lectures for gynecologic oncology was 'New Concepts in Epithelial Ovarian Cancer' encompassing the debate of adopting upfront surgery or chemotherapy for advanced ovarian cancer. In this context, individual lectures covered neoadjuvant chemotherapy, upper abdominal surgery, secondary cytoreduction, and new chemotherapy options. Choosing initial treatment modality depends largely on the tumor burden of given patient and building a prediction model for resectability of ovarian cancer might be warranted as Sokbom Kang suggested. Kimio Ushijima summarized recent trial results of chemotherapy for recurrent ovarian cancer dedicating large part to the molecular targeting agents such as vascular endothelial growth factor (VEGF) inhibitors, Ang1 and 2 receptor inhibitors, and PARP inhibitors. Bevacizumab, which is anti-VEGF and one of the most vigorously tested targeting agent, showed the promising results by GOG 218 and ICON7, again recently turned out to improve response rate and extend progression-free survival when combined with gemcitabine and carboplatin in platinum sensitive recurrent ovarian cancer on OCEANS trial. Four special lectures were given under the theme of 'Unresolved Issues in Endometrial Cancer'. Fertility preservation is widely advocated in recent years because the prognosis is excellent when diagnosed in early endometrial cancer even if the prevalence is relatively low (2.1-14.4%) in women under the age of 40. Still, the selection of patient, assessment of myometrial invasion, concurrent ovarian cancer, the formulation, dosage, duration of progestin-base regimen, monitoring response to progestin therapy, management for maintenance of complete response, and so forth are some of those awaits consensus formation. The Chang Gung Memorial Hospital group from Taiwan summarized the recent issues regarding fertility saving in early endometrial cancer along with presentation of their own data. Another aspect of conservative management of endometrial cancer being issued is whether to perform systemic lymph node dissection. While the risk evaluation by imaging modalities and histological typing/grading serves pivotal role in determining nodal metastasis, recent randomized controlled trials failed to demonstrate survival benefits in low risk patients. Thus Karen Chan concluded that a systemic lymphadenectomy can be safely avoided in the majority of low risk endometrial cancer patients. In contrast, widely accepted consensus about the adjuvant therapy in intermediate- or high-risk endometrial carcinoma is still far from established, although the role of chemotherapy is recently more recognized in adjuvant setting. The gestational trophoblastic neoplasia is a big health threat in many Asian countries in spite of dramatic decrease of prevalence in selected area for the last two decades. After reviewing intensively four randomized controlled trials and four case control studies, Taek-Sang Lee concluded that pulsed dactinomycin might be superior to weekly parenteral methotrexate warranting rigorously designed randomized trials. Six gynecologic cancer topics were presented orally. Notably, Ju-Won Roh presented 'clinical significance of EZH2 expression and therapeutic effect of its silencing in endometrial cancer', leading to receiving Merit Award. EZH2, which is a member of Polycomb-group (PcG) family acting mainly as a gene silencer, is a surrogate target for therapy because it is overexpressed in a number of malignancies and the relevancy with endometrial cancer has not been elucidated. She examined therapeutic effect of in vivo EZH2 silencing alone using siRNA or combined with chemotherapy and showed that EZH2 silencing enhanced cytotoxicity of paclitaxel, docetaxel and cisplatin in endometrial cells and suppressed tumor growth. 10th International Conference of ACOS was crowded with 1,450 delegates from 30 countries. The organizing committee declared it was the most successful one ever among the ACOS conferences so far and vowed to keep the momentum of international exchange.

Fertility-preserving treatment with progestin, and pathological criteria to predict responses, in young women with endometrial cancer

There are therapeutic dilemmas regarding conservative management of endometrial cancer in young women. We planned a prospective study to conservatively treat women aged under 40 years with clinical stage 1A, grade 1 endometrioid adenocarcinoma from 1999 to 2005. There were nine women (aged 28-40) who fulfilled the criteria, and medroxyprogesterone acetate (400 mg/day) was continued for 6 months. Curettage materials were pathologically evaluated according to our criteria including partial response (PR) (a small amount of cancer tissue with remarkable hormonal effects or atypical hyperplasia). To predict complete response (CR) to progestin, immunohistochemical staining for insulin-like growth factor type 1 receptor, phosphatase and tensin homolog deleted on chromosome ten, progesterone receptor (PgR), estrogen receptor and Ki67 were assessed. Seven (78%) and two cases presented complete and PRs, respectively. Two patients developed recurrent disease 10 and 22 months after the last dilatation and curettage, and both had synchronous ovarian cancer. However, all nine patients were alive and disease-free for a mean of 39 months. Of eight married patients, four (50%) conceived and three delivered full-term singletons. CR was related to positive expression of PgR (P=0.008). Patients with an initial PR can obtain CR after further treatment, and the PgR may be useful in predicting CR to fertility-preserving treatment in young women with endometrial cancer.

Endometrial cancer and fertility

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. 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. 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.

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.

Pregnancy following intracytoplasmic sperm injection and preimplantation genetic diagnosis after the conservative management of endometrial cancer

A rare case of a patient with conservatively treated endometrial carcinoma who conceived and delivered a healthy baby after the transfer of embryos with intracytoplasmic sperm injection (ICSI) and preimplantation genetic diagnosis (PGD) is presented. A 41-year-old woman had an office hysteroscopy in the infertility work-up and stage I endometrial adenocarcinoma was diagnosed. After conservative treatment, the patient underwent ICSI and PGD. She achieved pregnancy with two normal embryos. Two gestational sacs were observed but one of them was blighted. The patient subsequently delivered a healthy female infant. Repeated office hysteroscopy and endometrial sampling was performed after delivery. The appearance of the endometrium was normal on hysteroscopy, and the histology report was normal. The principal concern with medical therapy is that the lesion cannot be fully evaluated until the hysterectomy is performed, the nodes palpated, and the uterus is sectioned. The patient was referred to a gynaecological oncologist for definitive surgery.

The role of MRI in the conservative management of endometrial cancer

Background. Young patients with endometrial cancer who desire to preserve their fertility often decline hysterectomy in favor of conservative progestin therapy. Proper candidates should have disease confined to the uterus and a well-differentiated tumor. One of the evolving techniques to evaluate the extent of the disease and myometrial or cervical invasion is magnetic resonance imaging (MRI). Case. A young patient with early-stage endometrial cancer initially declined surgery and was treated with megestrol. MRI suggested myoinvasion, and the patient consented to surgical staging. The final pathology revealed no residual carcinoma. Conclusions. The accuracy of MRI in detecting myoinvasion is limited, and as such results should be interpreted with caution when this information is used in counseling a young patient regarding surgical staging for endometrial cancer.

Outcome of Fertility-Sparing Treatment With Progestins in Young Patients With Endometrial Cancer

In Brief OBJECTIVE To evaluate the safety of fertility-sparing hormonal therapy for endometrial cancer in young patients. METHODS We reviewed the clinical and pathologic records of patients diagnosed with endometrial adenocarcinoma before the age of 40, who were treated and followed over a 30-year period in the Division of Gynecologic Oncology. All patients who underwent conservative management with progestins (n = 13) are the subjects of this study. RESULTS Follow-up was available for all 13 patients, with a mean follow-up of 82 months. All patients responded to treatment within a mean period of 3.5 months, with normal pathology on follow-up endometrial samplings. Six patients had a recurrence within a period extending between 19 and 358 months (median 40 months). Four patients were treated with a second course of progestins, and all had a histologic complete response. As of the time of preparation of this report, nine healthy infants had been born, and all the patients remained without evidence of disease. CONCLUSION Conservative management of well-differentiated endometrial carcinoma in young patients, combined with assisted reproductive technologies, if needed, does not seem to worsen the prognosis. This approach also provides the possibility of conceiving and carrying a normal pregnancy. Conservative management of endometrial cancer in young patients with progestins allows fertility and does not seem to worsen the outcome.

Successful in vitro fertilization pregnancy after conservative management of endometrial cancer

Objective: To report a successful IVF pregnancy in an infertile couple after conservative treatment of endometrial cancer.Design: Case report and literature review.Setting: University teaching hospital.Patient(s): A 29-year-old infertile white woman.Main Outcome Measure(s): Successful pregnancy after conservative management of endometrial cancer.Intervention(s): Grade 1 endometrial adenocarcinoma diagnosed at hysteroscopy, followed by dilatation and curettage (D&C). On follow-up D&C, pathologic examination was normal after high-dose progesterone therapy. The patient subsequently underwent an IVF cycle with transfer of three blastocysts.Result(s): The patient delivered triplets by cesarean section. Laparoscopic-assisted vaginal hysterectomy and bilateral salpingo-oophorectomy was then done. No residual endometrial cancer was evident in the hysterectomy specimen, but a 1.1-cm cystic mixed endometrioid and clear cell-type adenocarcinoma was discovered in the left ovary. The patient is doing well after 3 cycles of chemotherapy; her CA-125 level is normal. The triplets are also doing well.Conclusion(s): In carefully chosen situations, deferring surgery in infertile patients with endometrial cancer may be a viable option permitting subsequent successful pregnancy.