Ovarian metastasis in women with clinical stage I endometrial carcinoma

BACKGROUND: The incidence of ovarian metastasis in women with clinical stage I endometrial carcinoma is generally reported to be 5%, leading to the practice of removing the ovaries at surgery even in young patients. METHODS: A retrospective study of 84 patients with clinical stage I endometrial cancer was carried out. Patients were excluded if the pathologic study revealed any evidence of extrauterine, apart from adnexal, spread or if the peritoneal cytology was positive. Patients with serous papillary or clear cell tumor histology were also excluded. RESULTS: Sixty-seven patients fulfilled the inclusion criteria. Only three (4%) patients were found to be in surgical stage IIIA, all three had grade 3 tumors. Of these patients, two had uterine serosal involvement and one had a microscopic tumor implant in a fallopian tube; none had ovarian metastasis. CONCLUSIONS: The risk of ovarian metastasis in women with well to moderately differentiated endometrial cancer, myometrial invasion limited to less than one half of the myometrium, negative peritoneal cytology and no evidence of metastatic lymph node spread is negligible. Young patients with a preoperative histological diagnosis of well to moderately differentiated endometrial carcinoma may be surgically staged, leaving the final decision regarding removal of the ovaries pending a thorough pathological review of the surgical specimens.     

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.     

Synchronous primary cancers of the endometrium and ovary in young women: A Korean Gynecologic Oncology Group Study

Objective

Some authors have recommended the use of diagnostic laparoscopy as a pretreatment assessment step for conservative hormonal treatment in young women with endometrial cancer. The aim of this study was to determine the incidence of synchronous primary cancer of the endometrium and ovary in young women.

Methods

The medical records of 3240 patients with endometrial cancer who underwent primary surgery between 1995 and 2010 were collected from 7 institutions and were retrospectively reviewed. Low-risk endometrial cancer was defined as tumors without myometrial invasion; normal or benign-looking ovaries; normal CA-125; grade 1 endometrioid histology; and early stage endometrial cancer on pretreatment assessment.

Results

Fifteen percent (471/3240) were younger than 40 years of age. The incidence of synchronous ovarian cancer in young women with endometrial cancer was 4.5% (21/471). In patients with low-risk endometrial cancer, synchronous cancers were not identified.

Conclusion

The incidence of synchronous ovarian malignancies in young women with endometrial cancer was quiet low (4.5%), unlike previous studies have revealed (11–29%). Therefore, diagnostic laparoscopy is not mandatory in patients with low-risk early stage endometrial cancer selected for conservative treatment to confirm the absence of ovarian malignancy.     

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。     

子宫内膜癌保留生育功能的治疗

对于年轻未生育子宫内膜癌患者的治疗目前存在较多争议。文章结合临床实践体会和文献报道,重点就其适应证选择、治疗前评估、治疗方案、疗效评价、病情监测、治疗后的生育问题、完成生育后的处理等做一阐述。     

Treatment of ovarian cancer in young women

Ovarian cancer accounts for approximately 22,000 cases annually in the United States. Although the vast majority of ovarian cancers occur in postmenopausal women and are of advanced stage, a significant subset occurs in young women. Among those subtypes having a predisposition for young women are malignant ovarian germ cell tumors, sex cord-stromal ovarian tumors, and tumors of low malignant potential. However, invasive epithelial ovarian cancers may also occur in young women, particularly the subtypes of low-grade serous carcinoma and mucinous carcinoma. This article details the diagnosis and optimal treatment of ovarian cancers subtypes in young women.     

Synchronous primary neoplasms of the female reproductive tract

A histopathologic review of synchronous primary neoplasms of the female reproductive tract is presented. During a 30-year period, 3863 patients with female genital malignancies were accessioned to the UCLA Tumor Registry: 958 had ovarian cancer, 776 endometrial cancer, 1556 cervical cancer, and 573 other gynecologic malignancies. Twenty-six (0.7%) patients with invasive synchronous primary cancers were identified. The most frequent synchronous genital lesions were ovarian and endometrial cancers in 11 patients (0.3%). No association was documented between genital and extragenital cancers. Patients with synchronous ovarian and endometrial cancers each were low stage and low grade, and the prognosis was excellent. Their detection in a relatively early stage suggests diagnosis may be facilitated by early symptoms from the endometrial carcinoma, and that these lesions are biologically of relatively low grade. These data support the conclusion that there is an association between low-stage epithelial carcinoma of the ovary and endometrial carcinoma.     

Reevaluating the safety of fertility-sparing hormonal therapy for early endometrial cancer

OBJECTIVE: To evaluate the safety of fertility-sparing hormonal therapy for endometrial cancer in young patients. METHODS: Six patients diagnosed with endometrial adenocarcinoma grade I and had undergone progestin treatment were reviewed. Four patients failed progestin treatment and were then found at surgery to have both endometrial and ovarian cancers. A clonality assay using the human androgen receptor gene as the X-linked polymorphic marker and immunohistochemistry for steroid hormone receptor expression were used to delineate the relation between the endometrial and ovarian lesions and to explore possible causes of treatment failure. RESULTS: The patients were followed for a mean of 48.8 months. Four of the six responded to the treatment at a mean of 3.5 months. Two of these patients had a recurrence within a mean of 4.5 months after their initial response. Two patients did not respond to progestin treatment. At surgery in those 4, both endometrial and ovarian tumors were found. All 6 are still alive, and 2 successfully delivered healthy infants. The clonality assay revealed an independent cell origin for the endometrial and ovarian lesions in 2 of the 4 women who failed progestin treatment. Progesterone receptors were absent in both endometrial and ovarian tumors in 2 of these 4 patients. CONCLUSION: The absence of progesterone receptors may relate to the failure of progestin treatment. The use of progestin treatment for well-differentiated early endometrial carcinoma should be cautious and requires very careful clinical evaluation before and after treatment.     

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.     

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.     

Fertility-preserving surgical procedures, techniques

As a result of the trend toward late childbearing, fertility preservation has become a major issue in young women with gynaecological cancer. Fertility-sparing treatments have been successfully attempted in selected cases of cervical, endometrial and ovarian cancer, and gynaecologists should be familiar with fertility-preserving options in women with gynaecological malignancies. Options to preserve fertility include shielding to reduce radiation damage, fertility preservation when undergoing cytotoxic treatments, cryopreservation, assisted reproduction techniques, and fertility-sparing surgical procedures. Radical vaginal trachelectomy with laparoscopic lymphadenectomy is an oncologically safe, fertility-preserving procedure. It has been accepted worldwide as a surgical treatment of small early stage cervical cancers. Selected cases of early stage ovarian cancer can be treated by unilateral salpingo-ophorectomy and surgical staging. Hysteroscopic resection and progesterone treatment are used in young women who have endometrial cancer to maintain fertility and avoid surgical menopause. Appropriate patient selection, and careful oncologic, psychologic, reproductive and obstetric counselling, is mandatory.     

Simultaneous appearance of ovarian and endometrial carcinoma: a therapeutic challenge

We have analyzed 37 cases of simultaneous appearance of carcinoma in the ovary and endometrium. This paper deals with the question of whether they should be considered stage III endometrial carcinomas, stage II ovarian carcinomas or independent primary tumors. The cases were grouped according to their histology as endometrioid ovarian carcinomas with endometrial carcinoma (group A), same carcinoma, but not of endometrial origin in both organs (group B) and histologically different concomitant carcinomas of ovary and endometrium (group C). Although our series was small, the survival was better than could have been expected either for stage III endometrial carcinoma, or stage II ovarian carcinoma. This supports the view that many of those tumors should be considered independent stage I carcinomas. Another fact in favour of this hypothesis is the strong correlation between myometrial invasion and prognosis in these cases, which is comparable to that found in endometrial carcinoma alone.     

Synchronous primary cancers of the endometrium and ovary: a single institution review of 84 cases

OBJECTIVES: Synchronous primary cancers of the endometrium and ovary are found in 10% of women with ovarian cancer and 5% of women with endometrial cancer. The purpose of this study was to characterize patients diagnosed with synchronous primary cancers of the endometrium and ovary with an emphasis on risk factors. METHODS: Between 1989 and 2002, 84 patients with synchronous primary cancers of the endometrium and ovary were identified. Patients with uterine papillary serous carcinoma were excluded. Clinical and pathologic information was obtained from medical records. Parametric methods were used to compare clinical and pathologic features. Kaplan-Meier survival analyses were performed and compared using the log rank test. RESULTS: Median age at diagnosis was 50 years. Median body mass index (BMI) was 28 kg/m(2). Fifty-one percent (43/84) of the women were premenopausal and 33% (28/84) were nulliparous. The most common presenting symptom was abnormal vaginal bleeding; in those women with abnormal vaginal bleeding, 69% had stage I ovarian cancer. Ovarian cancer was an incidental finding in 48% of these patients. Sixty-eight percent of patients (57/84) had endometrioid histology of both their endometrial and ovarian cancers. Patients with early stage ovarian cancer tended to have a more favorable prognosis than those with advanced stage disease (median survival not reached in stage I and II versus 66 months in stage III and IV, P = 0.06). Patients with concordant endometrioid histology had a favorable prognosis (median survival 119 versus 48 months in all other groups, P = 0.02). CONCLUSIONS: In this large series of patients, women with synchronous primary cancers of the endometrium and ovary were young, obese, nulliparous, and premenopausal. Patients with concordant endometrioid tumors of the endometrium and ovary had a favorable prognosis, with median survival approaching 10 years.     

Transvaginal color Doppler imaging for hemodynamic assessment of reproductive tract tumors.

Transvaginal color Doppler flow imaging was carried out on 68 Japanese women (normal, 10; uterine myoma, 21; cervical carcinoma, 7; endometrial carcinoma, 10; benign ovarian tumor, 12; ovarian carcinoma, 8). Blood flow velocity waveforms were evaluated by calculation of the resistance index (RI). In 6 patients with cervical carcinoma neovascularization was evident within the cervix. In all patients with endometrial carcinoma such signs were present adjacent to and/or within the endometrium. These findings were absent in normal women and in those with myomata. There was a significant difference between the RI (0.510 +/- 0.097) in patients with cervical carcinoma and in normal women (0.881 +/- 0.048) in the ascending branch. In endometrial carcinoma the RI (0.535 +/- 0.158) was significantly lower in the arcuate artery compared to the normal uterus (0.768 +/- 0.075) and patients with uterine myoma (0.679 +/- 0.131), respectively. There was no area of neovascularization in the normal ovaries. Neovascularization was confirmed in four patients with a benign ovarian tumor and in all patients with an ovarian carcinoma. A significantly lower RI was obtained in cases of ovarian carcinoma (0.503 +/- 0.122) than in patients with benign ovarian tumors (0.888 +/- 0.216). Transvaginal color Doppler imaging and pulsed Doppler analysis may be useful diagnostic tools to differentiate benign and malignant tumors.     

The combined GnRH-agonist and intrauterine levonorgestrel-releasing system treatment of complicated atypical hyperplasia and endometrial cancer: a pilot study

In this article, we present the results of organ-preserving treatment applied in 24 patients of reproductive age with atypical endometrial hyperplasia or early-stage endometrial cancer. All of them would like to preserve their reproductive potential. Thirteen women with atypical endometrial hyperplasia were treated with the combination of six intramuscular injections of 3.75?mg gonadotropin-releasing hormone agonist (GnRHa) ? leuproreline acetate depot every 4 weeks. After the third injection of 3.75?mg of leuproreline acetate, the levonorgestrel intrauterine hormonal system containing 52?mg levonorgestrel (Mirena^®, Bayer, Germany) was inserted for at least 6 months. In 11 women with stage IA well-differentiated endometrial adenocarcinoma, hormonal therapy included nine intramuscular injections of 3.75?mg of GnRHa every 4 weeks. After the third injection of 3.75?mg of GnRHa, we also inserted a GnRH-IUS (Mirena^®) for at least 12 months. This type of therapy was effective for all these patients and may be offered to be used as an alternative to surgery in women with atypical endometrial hyperplasia or early stage 1A well-differentiated endometrial cancer in women of reproductive age. Three women with endometrial cancer became pregnant and two of them delivered at term and one has an ongoing pregnancy.     

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     

Fertility sparing therapy for ovarian cancer has inherent risks and benefits

Introduction: Fertility sparing therapy for epithelial ovarian cancer has been suggested for well-selected patients with early stage disease. The overall recurrence rate of 10% and 5-year disease free survival greater than 90% is similar in conservative and traditional surgical management of epithelial ovarian cancer. Thus, conservative approaches may be considered in young women diagnosed with FIGO stage I cancer who wish to preserve reproductive function. Subsequent use of assisted reproductive technologies (ART) may facilitate production of biologic offspring in these cancer survivors. However, each candidate requires unique consideration by subspecialists to avoid potentially fatal management errors. Case report: We present two cases in which fertility sparing therapy for early stage epithelial ovarian cancer was considered. The first case delineates the comprehensive work-up required to identify candidates for this therapy, while the second case illustrates the successful application of a fertility sparing approach. Discussion: The conservative management of early epithelial ovarian cancer and use of ART to obtain offspring are reviewed.     

Borderline ovarian tumors in reproductive-age women. Fertility-sparing surgery and outcome

OBJECTIVE: To evaluate the fertility and survival outcomes in young women with borderline ovarian tumors treated with fertility-sparing surgery. STUDY DESIGN: From 1985 to 2002, 25 women with borderline ovarian cancers surgically managed with preservation of the uterus and at least a portion of 1 ovary were identified from tumor registry databases at 2 southern California hospitals. Data for analysis were collected from hospital charts, office records and tumor registry files. RESULTS: Twenty-five patients (median age, 29 years) with borderline ovarian tumors, including 10 with stage IA, 3 with stage IC, 1 with stage IIIA and 11 with unstaged disease, underwent fertility-sparing surgery, consisting of unilateral adnexectomy in 19, unilateral adnexectomy with contralateral cystectomy in 5 and unilateral cystectomy in 1. No disease recurred, providing an overall survival of 100%. Fertility status was available on 15 patients 4-157 months after surgery; 6 of them attempted to become pregnant. Five women had successful pregnancies, with a total of 5 live births. One woman underwent assisted reproductive techniques, became pregnant but aborted. The median follow-up was 80 months (range, 4-157). CONCLUSION: Conservative surgery for borderline ovarian tumors should be considered for women in the reproductive age group who desire preservation of fertility.     

Ovarian tumors in the reproductive age group

OBJECTIVES: Analysis of the type and localization of the ovarian tumors in the reproductive age group of women. MATERIALS AND METHODS: The study group consisted of all women operated on Gynecologic Surgery Department of Polish Mothers's Memorial Hospital-Research Institute due to ovarian tumors in 1996-99. As the reproductive age we defined 18-39 year, when the majority of deliveries occurs. RESULTS: We analyzed 326 patients operated on the ovarian tumors. In 60 cases (18.4%) we noticed ovarian malignant tumors, in 7 (2.1%) borderline tumors and in 259 (79.5%) benign cysts. In the reproductive age (130 women) the incidence of ovarian malignancies was significantly lower (4.6%), higher for benign tumors (93.1%) and constant for borderline malignancy (2.3%), p < 0.005. The most common malignancy among all patients was epithelial cancer--83.4% (germ cell and metastatic--8.3%, both), but in the reproductive age group (6 cases) germ cell tumors were the majority--66.8% (epithelial and metastatic--16.6%, both), p < 0.005. In women aged 18-39 yr. with ovarian malignancies 4 of them had I stage of the disease and 2 were in the stage III. 121 women in the reproductive age were operated on the benign ovarian tumors; 107 (88.4%) had unilateral cysts and 14 (11.6%) had tumors in both ovaries. On histology we revealed 31.1% of endometrioid cysts, 28.9%--teratomas, 19.3%--serous, 3.7%--mucinous and others (hemorrhagic, functional, sex cord, inflammatory) in the remaining 17%. CONCLUSION: In the reproductive age ovarian tumors are mainly unilateral benign cysts. Only a few of ovarian tumors were malignant but the majority of them were in the early stage of the disease.     

Chien-Tien Hsu Memorial Lecture. Fertility and gynaecologic malignancies

Fertility and gynaecological malignancies have an important relationship. A clear inverse relationship exists between family size and the incidence of ovarian and endometrial cancer. Current methods of fertility control have an influence on subsequent development of various gynaecological malignancies. A slightly increased risk of breast cancer has been reported in current users and those who had used hormonal contraceptives (OCs) within 10 years; this risk declined with time and disappeared after 10 years. Women who started OC before age 20 had a higher relative risk; the disease did not spread beyond the breast in the majority. Most studies found OC to reduce the risk of ovarian and endometrial cancer. The relative risks of squamous cell carcinoma and adenomatous carcinoma of the cervix have been reported to be 1.3 and 1.5, respectively in ever-users of OCs; however, the aetiology of cervical cancer is multifactoral. Several reports suggest the beneficial effect of tubal ligation and breast feeding in reducing the risk of ovarian cancer. Therapy of gynaecological malignancies may have an influence on subsequent fertility. Amenorrhoea developing after treatment of hydatidiform mole may be due to choriocarcinoma, recurrent mole or a normal pregnancy. Choriocarcinoma can also develop after a partial mole. The risk of fetal teratogenicity from chemotherapy is present only if conception occurs during or immediately following the treatment cycles. Fertility is not impaired following chemotherapy. Successful pregnancies have occurred in women who have had widespread GTD including cerebral metastases. In the young patient with gynaecological malignancy preservation of fertility is possible. Fertility-sparing surgery may be safe in early ovarian epithelial cancers and even in advanced germ cell tumours. Recently, the fertility-sparing surgery of radical trachelectomy and pelvic lymphadenectomy has been carried out for early invasive cervical cancer in young women. Gynaecological cancer occurring in pregnancy is uncommon; it presents the clinician with a difficult situation to manage. In most instances the cancer is treated as though the patient is not pregnant; the timing and mode of delivery needs individualization. The overall prognosis for breast cancer complicating pregnancy is poor. Survival in cervical cancers diagnosed antepartum is similar to the non-pregnant patient. Ovarian cancer in pregnancy has a good prognosis because of the early stage at diagnosis.