eMedicine Specialties > Obstetrics and Gynecology > Gynecologic Oncology
Uterine Cancer
Updated: Jun 4, 2009
Introduction
Invasive neoplasms of the female pelvic organs account for almost 15% of all cancers in women. The most common of these malignancies is uterine cancer, specifically, endometrial cancer. Endometrial cancer is the most common gynecologic malignancy in the United States. An estimated 40,100 cases are diagnosed annually, leading to 7470 deaths. It is the fourth most common cancer, accounting for 6% of female cancers, following breast, lung, and colorectal cancer. However, it has a favorable prognosis because the majority of patients present at an early stage, resulting in only 3% of cancer deaths in women.1
History of the Procedure
Cancer of the uterine corpus is the most common pelvic gynecologic malignancy in the United States and in most developed countries with access to sufficient health care. Approximately 95% of these malignancies are carcinomas of the endometrium. The most common symptom in 90% of women is postmenopausal (PMP) bleeding. Most women recognize the need for prompt evaluation, although only 10-20% of women with postmenopausal vaginal bleeding have a gynecologic malignancy. Because of this prompt evaluation, 70-75% of women are diagnosed with surgical stage I disease.
Currently, no screening tests for cancer of the uterus are recommended for asymptomatic women. No evidence suggests that routine endometrial sampling or transvaginal sonography to evaluate the endometrial stripe in asymptomatic women has a role in early detection of uterine cancer, even in women who take tamoxifen after breast cancer. The early detection, presenting symptoms, and higher survival rate make it unlikely that screening will have a successful impact on earlier detection and increased survival rate.
Sixty percent of endometrial carcinomas are adenocarcinomas. Other histologic subtypes include adenosquamous, clear cell, and papillary serous carcinomas. Sarcomas make up about 4% of uterine corpus malignancies, including carcinosarcomas or mixed homologous müllerian tumors, 48-50%; leiomyosarcomas (LMSs), 38-40%; and endometrial stromal sarcomas (EESs), 8-10%. The remaining sarcomas are made up of heterologous tumors—tumors that contain histologic components foreign to the uterus, such as rhabdomyosarcomas, osteosarcomas, and chondrosarcomas. This article discusses endometrial cancer and uterine sarcomas.
Adenocarcinoma of the endometrium. This tumor, which occupies a small uterine cavity, grows primarily as a firm polypoid mass.
Problem
Uterine cancer is defined as any invasive neoplasm of the uterine corpus.
Frequency
Approximately 40,100 women were predicted to develop this form of malignancy in 2008 in the United States. After doubling in the early 1970s, the incidence of uterine cancer has remained fairly constant. In 2008, 7,470 deaths were predicted.
While endometrial cancer affects reproductive age as well as postmenopausal women, 75% of endometrial cancers occur in postmenopausal women, with the mean age of diagnosis at 61 years. Premenopausal women are at increased risk if they have certain risk factors.2 The most common low-grade endometrioid endometrial cancers have been associated with obesity, nulliparity, anovulatory menstrual cycles, diabetes, and hypertension. In addition, these younger women are at higher risk for a synchronous primary ovarian cancer, with a rate up to 19-25%.2,3
Another group of women at increased risk of premenopausal endometrial cancer are those with Lynch II syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC). This is an autosomally dominant germline mutation in DNA mismatch repair (MMR) genes (MSH1, MSH2, MSH6) and accounts for 9% of patients younger than 50 years with endometrial cancer. These mutations lead to microsatellite instability in 90% of colon cancers and 75% of endometrial cancers. Besides colon cancer, women affected have a 40-60% risk of endometrial cancer by age 70 years, compared to a baseline population risk of 1.5% at the same age. Fifty-one percent of women had endometrial or ovarian cancer diagnosed first as the sentinel cancer. These women are also at increased risk for cancer of the ovary, stomach, small bowel, hepatobiliary system, pancreas, brain, breast, and ureter or kidney.4,5
Incidence of endometrial cancer is higher among Caucasians compared with Asian or black women; however, mortality is higher among blacks. This is thought to be due to poor access to care and presentation at more advanced stages.
Uterine sarcomas, regardless of the histologic subtype, are more common in black women. Leiomyosarcoma (LMS) tends to occur more often in women aged 30-50 years compared with carcinosarcomas and endometrial stromal sarcomas (EES), which have a much higher incidence in women older than 50 years.
Etiology
Endometrioid adenocarcinoma can be due to excess estrogen from various sources, either exogenous or endogenous. Exogenous sources have included unopposed estrogen replacement therapy or tamoxifen use. Tamoxifen increases endometrial cancer risk by its agonist activity on the estrogen receptors on the endometrial lining. Endogenous estrogen sources include obesity and polycystic ovary syndrome (PCOS) with anovulatory cycles, or estrogen-secreting tumors such as granulose cell tumors. Increasing body mass index has been associated with increasing risk of endometrial cancer.6 Research has found a relative risk of 3 in women 21-50 lb overweight and relative risk over 10 in women more than 50 lb overweight. Androstenedione is converted to estrone, and androgens are aromatized to estradiol in the adipose tissue, leading to higher levels of unopposed estrogen in obese women. See Table 1.
Table 1. Factors Contributing to Endometrial Cancer
Open table in new window
Table
| Risk Factor | Number of Folds Increased Risk |
| Estrogen only hormone replacement therapy (HRT) | 2-10 |
| Obesity | 2-20 |
| PCOS, chronic anovulation | 3 |
| Tamoxifen | 2-3 |
| Nulliparity | 2-3 |
| Early menarche, late menopause | 2-3 |
| Hypertension, diabetes | 2-3 |
| Risk Factor | Number of Folds Increased Risk |
| Estrogen only hormone replacement therapy (HRT) | 2-10 |
| Obesity | 2-20 |
| PCOS, chronic anovulation | 3 |
| Tamoxifen | 2-3 |
| Nulliparity | 2-3 |
| Early menarche, late menopause | 2-3 |
| Hypertension, diabetes | 2-3 |
The other factors associated with increasing one’s risk of endometrial cancer are believed to be related to the same mechanism of increased levels of unopposed estrogen. Nulliparity and infertility are likely related to chronic anovulation. Increased alcohol use can elevate estrogen levels. Late menopause and early menarche can be associated with more anovulatory cycles and thus more unopposed estrogen.
While there is no evidence that screening for endometrial cancer in high-risk populations, such as patients on tamoxifen or patients who have HNPCC syndrome, decreases mortality, some societies advocate screening with endometrial biopsies starting at age 35 years in patients with HNPCC.
Factors that decrease unopposed estrogen are associated with decreased risk of endometrial cancers. The use of combination oral contraceptive pills for 12 months decreases the risk of endometrial cancer by more than 40%.7 Similarly, postmenopausal women taking the combined estrogen and progesterone hormone replacement therapy have also been found to decrease their rate of endometrial cancer.8 Smoking is thought to decrease the risk of endometrial cancer by decreasing estrogen levels as well as leading to earlier menopause.
The following have been identified as risk factors for the various uterine sarcomas. Risk factors for uterine LMS may include early menarche, late menopause, and African American race. Women with a history of pelvic radiation are at greatest risk for carcinosarcomas and, to a lesser extent, LMS. Nulliparous women may be at greater risk for both types of sarcomas.
Pathophysiology
Endometrial cancers are divided into 2 classes, each with differing pathophysiology and prognosis.
More than 80% of endometrial carcinomas are type I and are due to unopposed estrogen stimulation, resulting in a low-grade histology. It is often found in association with atypical endometrial hyperplasia, which is thought to be a precursor lesion. Type II endometrial cancers are thought to be estrogen independent, occurring in older women, with high-grade histologies such as uterine papillary serous or clear cell.
Endometrial cancer may originate in a small area (eg, within an endometrial polyp) or in a diffuse multifocal pattern. Early tumor growth is characterized by an exophytic and spreading pattern. As noted in Clinical, this growth is characterized by friability and spontaneous bleeding, even at early stages. Later tumor growth is characterized by myometrial invasion and growth toward the cervix. Four routes of spread occur beyond the uterus:
- Direct/local spread accounts for most local extension beyond the uterus.
- Lymphatic spread accounts for spread to pelvic, para-aortic, and, rarely, inguinal lymph nodes.
- Hematologic spread is responsible for metastases to the lungs, liver, bone, and brain (rare).
- Peritoneal/transtubal spread results in intraperitoneal implants, particularly with uterine papillary serous carcinoma (UPSC), similar to the pattern observed in ovarian cancer.
Adenocarcinoma of the endometrium, the most common histology, is usually preceded by adenomatous hyperplasia with atypia. If left untreated, simple and complex endometrial hyperplasia with atypia progress to adenocarcinoma in 8% and 29% of cases, respectively. Without atypia, simple and complex hyperplasia progress to cancer in only 1% and 3% of cases, respectively.
Typical histologic pattern, specifically cribriform glandular appearance, of endometrioid adenocarcinoma of the endometrium. Increased nuclear atypia and mitotic figures are present.
Endometrial adenocarcinoma is histologically characterized by cribriform glands (or glandular crowding) with little, if any, stromal tissue between the glands. Nuclear atypia, variation in gland size, and increased mitoses are common in adenocarcinoma. Well-differentiated tumors may be confused with complex hyperplasia with atypia histologically. Likewise, poorly differentiated tumors might be confused with sarcomas histologically. All papillary serous and clear cell histologies are considered grade 3. The differentiation of endometrial cancers is one of the most important prognostic factors. Grade 1, 2, and 3 tumors make up approximately 45%, 35%, and 20%, respectively, of adenocarcinomas of the endometrium. The 5-year survival rate of clinical stage I cancers is 94%, 88%, and 79% for grade 1, 2, and 3 tumors, respectively. The degree of histologic differentiation of adenocarcinoma of the endometrium as defined by the International Federation of Gynecology and Obstetrics (FIGO) is as follows:
- FIGO grade 1 - 5% or less of solid/nonglandular areas
- FIGO grade 2 - 6-50% of solid/nonglandular areas
- FIGO grade 3 - More than 50% of solid/nonglandular areas
Less histologic differentiation is associated with a higher incidence of deep (ie, greater than one half) myometrial invasion and lymph node metastases. Subsequently, the depth of myometrial invasion and presence of tumor in the lymph nodes is directly related to recurrence rates and 5-year survival rates.
Histological variants
The most common histologic subtype of endometrial cancer is endometrioid adenocarcinoma, accounting for about 75-80% of endometrial cancers. Less common histologies include adenosquamous (2%) and mucinous (2%). When corrected for grade, however, the presence of squamous components has not been demonstrated to cause a significant difference in prognosis compared to pure adenocarcinomas. PTEN mutation is thought to be an early event in low-grade endometrial cancers and is found in 55% of hyperplasia and 85% of cancers, whereas it is not found in benign endometrium.Approximately 15-20% of endometrial cancers are type II cancers with papillary serous or clear cell histologies. Papillary serous histology represents 5-10% and clear cell histology represents less than 5% of endometrial cancers. They are considered high grade with poor prognosis. They have a propensity for early nodal or upper abdominal spread even with minimal or no myometrial invasion. The p53 mutation is more common in high-grade tumors, and ERBB-2 (HER-2/neu) mutation is common in type II cancers. Even with surgical stage I cancer, the 5-year survival rate is 60%. Histologically, uterine papillary serous carcinoma (UPSC) resembles papillary serous carcinoma of the ovary. Although adjuvant chemotherapy is helpful, UPSC does not have the same duration of response to cytotoxic agents (eg, paclitaxel, carboplatin) as its ovarian counterpart.
In regards to uterine sarcomas, specifically LMS, the histopathologic diagnosis can be unclear until the time of definitive surgery. Diagnosis of LMS is dependent on the number of mitoses (or mitotic count) and the degree of cellular atypia. The diagnosis of LMS versus leiomyoma and leiomyoma with high mitotic activity or uncertain malignant potential is based on the metastatic potential of the tumor. The mitotic count and cellular atypia correlates to this metastatic potential.
Although controversy continues to exist regarding the diagnosis of LMS, several studies support the theory that if the mitotic count is less than 5 per 10 high-powered fields (HPF), the tumor is a leiomyoma with negligible metastatic potential regardless of the presence of any cellular atypia. Likewise, the tumor has a high metastatic potential and is considered an LMS, regardless of the degree of cellular atypia, if the mitotic count is greater than 10 per 10 HPF. Some believe that mitotic count alone is not a good indicator of metastatic potential.
Carcinosarcomas or homologous mixed müllerian tumors (MMT) typically have an endometrioid carcinoma, usually a higher grade, and an undifferentiated spindle cell sarcoma. The sarcomatous portion of the tumor may exhibit an endometrial stromal sarcoma (ESS) pattern, if differentiated. MMTs are termed heterologous only if identifiable extrauterine histology is demonstrated. MMTs are characterized by early extrauterine spread and lymph node metastases. Extrauterine disease and lymph node metastases are directly related to depth of myometrial invasion and the presence of cervical disease. The presence of heterologous elements does not seem to affect prognosis in terms of the initial extent of disease. New evidence points to a substantial expression of c-kit receptors in MMTs.
ESS can be divided into 2 categories: low-grade ESS (LGESS) and high-grade ESS (HGESS). LGESS is characterized by fewer than 5-10 mitoses per 10 HPF and minimal cellular atypia. These tumors can have a recurrence rate of up to 50% but demonstrate indolent growth and late recurrences. HGESS have a greater mitotic count and degree of cellular atypia. Risk of recurrence in both LGESS and HGESS is determined not only by histological characteristics but also by surgical stage and extent of disease.
Presentation
More than 90% of patients with endometrial cancer will present with abnormal vaginal bleeding, whether it is menorrhagia, metrorrhagia, or any amount of postmenopausal bleeding. Approximately 10% of postmenopausal bleeding will lead to a diagnosis of endometrial cancer. Advanced cases, especially patients with uterine papillary serous or clear cell histologies may present with abdominal pain and bloating or other symptoms of metastatic disease. Other presenting symptoms may include purulent genital discharge, pain, weight loss, and a change in bladder or bowel habits. Fortunately, most cases of endometrial cancer are diagnosed prior to this clinical presentation because of the recognition of postmenopausal (PMP) bleeding as a possible early symptom of cancer. About 5% of women may be asymptomatic and diagnosed after workup of abnormal Papanicolaou test results.
Uterine sarcomas can present in a similar fashion to endometrial carcinomas. Leiomyosarcoma (LMS) may present in women early in the sixth decade of life with irregular menses or PMP bleeding. Other symptoms include pain, pelvic pressure, and a rapidly enlarging pelvic mass. Unfortunately, the diagnosis is rarely made prior to definitive surgery. Endometrial stromal sarcoma (ESS) usually presents with PMP bleeding, pelvic pain, and an enlarging mass. Like mixed müllerian tumors (MMT), ESS typically presents in the seventh decade of life. Irregular and PMP bleeding are the most common symptoms of MMT also. Weight loss, anorexia, and change in bowel or bladder habits are signs of advanced disease in all cases of uterine cancer.
Indications
The mainstay of primary treatment in endometrial cancer and uterine sarcomas is surgery. Radiation has an important role in adjuvant treatment of endometrial cancers and sarcomas. Chemotherapy plays a role in adjuvant therapy for high-grade uterine sarcomas, in addition to recurrent or metastatic endometrial cancer. Hormonal therapy also has a role in adjuvant therapy in receptor-positive endometrial cancers. Details regarding all of these therapies are discussed later in this article.
Most endometrial cancers are diagnosed as stage I tumors. In fact, most endometrial cancer can be cured with surgery alone, and relatively few patients need adjuvant radiotherapy. In the past, surgery and radiation therapy were both used as primary therapy. Now, survival rates with surgery are known to be 15-20% better than with primary radiation therapy. Thus, primary radiation therapy is reserved only for patients who are poor surgical candidates or for those with unresectable disease.
Like endometrial cancer, primary surgical therapy is the first step in treatment of uterine sarcomas. In fact, these tumors are often found at the time of surgery for benign indications such as uterine leiomyomata and dysfunctional uterine bleeding, or they are found postoperatively. Approximately 1 of every 2000 women older than 40 years who are undergoing a hysterectomy for uterine leiomyomata have leiomyosarcoma (LMS) on final pathologic diagnosis.
Relevant Anatomy
See Multimedia section for relevant surgical anatomy.
Contraindications
In the rare cases of clinical stage I, grade 1 endometrial adenocarcinoma in young women who have not completed childbearing, an attempt can be made to preserve fertility with medical management after careful counseling regarding the potential risks. Full evaluation is needed to rule out higher stage or grade disease. Pelvic ultrasonography, a pelvic MRI, or both is necessary to assess approximate depth of invasion and to rule out adnexal pathology. A hysteroscopy D&C is also necessary to thoroughly sample the endometrial cavity and rule out large volume or higher-grade disease. Prospective and retrospective series report initial response rates of 50-75%, but many will recur. One study reports 25% have achieved pregnancies after conservative management.9,10 Recommendation is for definitive total abdominal hysterectomy (TAH), bilateral salpingo-oophorectomy (BSO), and possible staging with disease persistence, recurrence, or at completion ofchildbearing.
Some have suggested ovarian preservation after hysterectomy in young women wishing to preserve hormonal function and future childbearing through egg retrieval.11 This should be cautioned against due to risk of adnexal metastases or synchronous tumors, which occur in up to 25% of young women.3
Women with significant comorbidities who are not surgical candidates and have clinical stage I endometrial cancer can be managed by primary radiation. Although the survival rate with primary radiation alone is 15-20% less than with surgery, the morbidity and mortality from surgical therapy in some patients may outweigh the benefits gained in terms of survival and recurrence. Many of these women will die due to other comorbid conditions.12
More on Uterine Cancer |
 Overview: Uterine Cancer |
| Workup: Uterine Cancer |
| Treatment: Uterine Cancer |
| Follow-up: Uterine Cancer |
| Multimedia: Uterine Cancer |
| References |
| Next Page » |
References
Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin. Mar-Apr 2008;58(2):71-96. [Medline].
Soliman PT, Oh JC, Schmeler KM, et al. Risk factors for young premenopausal women with endometrial cancer. Obstet Gynecol. Mar 2005;105(3):575-80. [Medline].
Walsh C, Holschneider C, Hoang Y, Tieu K, Karlan B, Cass I. Coexisting ovarian malignancy in young women with endometrial cancer. Obstet Gynecol. Oct 2005;106(4):693-9. [Medline].
Lu KH, Schorge JO, Rodabaugh KJ, et al. Prospective determination of prevalence of lynch syndrome in young women with endometrial cancer. J Clin Oncol. Nov 20 2007;25(33):5158-64. [Medline].
Lu KH, Dinh M, Kohlmann W, et al. Gynecologic cancer as a "sentinel cancer" for women with hereditary nonpolyposis colorectal cancer syndrome. Obstet Gynecol. Mar 2005;105(3):569-74. [Medline].
[Best Evidence] Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet. Feb 16 2008;371(9612):569-78. [Medline].
The Cancer and Steroid Hormone Study of the Centers for disease Control and the National Institute of Child Health and Human Development. Combination oral contraceptive use and the risk of endometrial cancer. The Cancer and Steroid Hormone Study of the Centers for Disease Control and the National Institute of Child Health and Human Development. JAMA. Feb 13 1987;257(6):796-800. [Medline].
Doherty JA, Cushing-Haugen KL, Saltzman BS, et al. Long-term use of postmenopausal estrogen and progestin hormone therapies and the risk of endometrial cancer. Am J Obstet Gynecol. Aug 2007;197(2):139.e1-7. [Medline].
Ramirez PT, Frumovitz M, Bodurka DC, Sun CC, Levenback C. Hormonal therapy for the management of grade 1 endometrial adenocarcinoma: a literature review. Gynecol Oncol. Oct 2004;95(1):133-8. [Medline].
Ushijima K, Yahata H, Yoshikawa H, et al. Multicenter phase II study of fertility-sparing treatment with medroxyprogesterone acetate for endometrial carcinoma and atypical hyperplasia in young women. J Clin Oncol. Jul 1 2007;25(19):2798-803. [Medline].
Lee TS, Jung JY, Kim JW, et al. Feasibility of ovarian preservation in patients with early stage endometrial carcinoma. Gynecol Oncol. Jan 2007;104(1):52-7. [Medline].
Grigsby PW, Kuske RR, Perez CA, Walz BJ, Camel MH, Kao MS, et al. Medically inoperable stage I adenocarcinoma of the endometrium treated with radiotherapy alone. Int J Radiat Oncol Biol Phys. Apr 1987;13(4):483-8. [Medline].
Karlsson B, Granberg S, Wikland M, et al. Transvaginal ultrasonography of the endometrium in women with postmenopausal bleeding--a Nordic multicenter study. Am J Obstet Gynecol. May 1995;172(5):1488-94. [Medline].
Wang J, Wieslander C, Hansen G, Cass I, Vasilev S, Holschneider CH. Thin endometrial echo complex on ultrasound does not reliably exclude type 2 endometrial cancers. Gynecol Oncol. Apr 2006;101(1):120-5. [Medline].
ACOG Practice Bulletin #99. Management of abnormal cervical cytology and histology. December 2008.
Creasman WT, Odicino F, Maisonnueve P. FIGO Annual Report on the Results of Treatment in Gynaecological Cancer: Carcinoma of the corpus uteri. J Epidemiol Biostat. 1998;23(1):35-61.
Case AS, Rocconi RP, Straughn JM Jr, et al. A prospective blinded evaluation of the accuracy of frozen section for the surgical management of endometrial cancer. Obstet Gynecol. Dec 2006;108(6):1375-9. [Medline].
Chan JK, Cheung MK, Huh WK, et al. Therapeutic role of lymph node resection in endometrioid corpus cancer: a study of 12,333 patients. Cancer. Oct 15 2006;107(8):1823-30. [Medline].
Palomba S, Falbo A, Mocciaro R, Russo T, Zullo F. Laparoscopic treatment for endometrial cancer: a meta-analysis of randomized controlled trials (RCTs). Gynecol Oncol. Feb 2009;112(2):415-21. [Medline].
Havrilesky LJ, Cragun JM, Calingaert B, et al. The prognostic significance of positive peritoneal cytology and adnexal/serosal metastasis in stage IIIA endometrial cancer. Gynecol Oncol. Feb 2007;104(2):401-5. [Medline].
Bristow RE, Zerbe MJ, Rosenshein NB, Grumbine FC, Montz FJ. Stage IVB endometrial carcinoma: the role of cytoreductive surgery and determinants of survival. Gynecol Oncol. Aug 2000;78(2):85-91. [Medline].
Morrow CP, Bundy BN, Kurman RJ, et al. Relationship between surgical-pathological risk factors and outcome in clinical stage I and II carcinoma of the endometrium: a Gynecologic Oncology Group study. Gynecol Oncol. Jan 1991;40(1):55-65. [Medline].
Creutzberg CL, van Putten WL, Koper PC, Lybeert ML, Jobsen JJ, Warlam-Rodenhuis CC, et al. Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial. PORTEC Study Group. Post Operative Radiation Therapy in Endometrial Carcinoma. Lancet. Apr 22 2000;355(9213):1404-11. [Medline].
Scholten AN, van Putten WL, Beerman H, et al. Postoperative radiotherapy for Stage 1 endometrial carcinoma: long-term outcome of the randomized PORTEC trial with central pathology review. Int J Radiat Oncol Biol Phys. Nov 1 2005;63(3):834-8. [Medline].
Keys HM, Roberts JA, Brunetto VL, et al. A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. Mar 2004;92(3):744-51. [Medline].
Blake P, Swart AM, Orton J, et al. Adjuvant external beam radiotherapy in the treatment of endometrial cancer (MRC ASTEC and NCIC CTG EN.5 randomised trials): pooled trial results, systematic review, and meta-analysis. Lancet. Jan 10 2009;373(9658):137-46. [Medline].
[Best Evidence] Randall ME, Filiaci VL, Muss H, et al. Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol. Jan 1 2006;24(1):36-44. [Medline].
Fleming GF, Brunetto VL, Cella D, et al. Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol. Jun 1 2004;22(11):2159-66. [Medline].
Sovak MA, Hensley ML, Dupont J, et al. Paclitaxel and carboplatin in the adjuvant treatment of patients with high-risk stage III and IV endometrial cancer: a retrospective study. Gynecol Oncol. Nov 2006;103(2):451-7. [Medline].
Lupe K, Kwon J, D'Souza D, et al. Adjuvant paclitaxel and carboplatin chemotherapy with involved field radiation in advanced endometrial cancer: a sequential approach. Int J Radiat Oncol Biol Phys. Jan 1 2007;67(1):110-6. [Medline].
Fung-Kee-Fung M, Dodge J, Elit L, Lukka H, Chambers A, Oliver T. Follow-up after primary therapy for endometrial cancer: a systematic review. Gynecol Oncol. Jun 2006;101(3):520-9. [Medline].
Bloss JD, Berman ML, Bloss LP, Buller RE. Use of vaginal hysterectomy for the management of stage I endometrial cancer in the medically compromised patient. Gynecol Oncol. Jan 1991;40(1):74-7. [Medline].
Chi DS, Curtin JP. Gynecologic cancer and laparoscopy. Obstet Gynecol Clin North Am. Mar 1999;26(1):201-15. [Medline].
Christopherson WM, Alberhasky RC, Connelly PJ. Carcinoma of the endometrium. II. Papillary adenocarcinoma: a clinical pathological study, 46 cases. Am J Clin Pathol. May 1982;77(5):534-40. [Medline].
Creasman WT, Morrow CP, Bundy BN, Homesley HD, Graham JE, Heller PB. Surgical pathologic spread patterns of endometrial cancer. A Gynecologic Oncology Group Study. Cancer. Oct 15 1987;60(8 Suppl):2035-41. [Medline].
DiSaia PJ, Creasman WT, Boronow RC, Blessing JA. Risk factors and recurrent patterns in Stage I endometrial cancer. Am J Obstet Gynecol. Apr 15 1985;151(8):1009-15. [Medline].
Efange SM, Michelson RH, Knusel B, et al. Synthesis and biological evaluation of radioiodinated N-2-(4-piperidyl)ethyl benzamides. Nucl Med Biol. May 1993;20(4):527-38. [Medline].
Egarter C, Krestan C, Kurz C. Abdominal dissemination of malignant cells with hysteroscopy. Gynecol Oncol. Oct 1996;63(1):143-4. [Medline].
Gemignani ML, Curtin JP, Zelmanovich J, Patel DA, Venkatraman E, Barakat RR. Laparoscopic-assisted vaginal hysterectomy for endometrial cancer: clinical outcomes and hospital charges. Gynecol Oncol. Apr 1999;73(1):5-11. [Medline].
Granberg S, Wikland M, Karlsson B, Norstrom A, Friberg LG. Endometrial thickness as measured by endovaginal ultrasonography for identifying endometrial abnormality. Am J Obstet Gynecol. Jan 1991;164(1 Pt 1):47-52. [Medline].
Harlow BL, Weiss NS, Lofton S. The epidemiology of sarcomas of the uterus. J Natl Cancer Inst. Mar 1986;76(3):399-402. [Medline].
Hawwa ZM, Nahhas WA, Copenhaver EH. Postmenopausal bleeding. Lahey Clin Found Bull. Apr-Jun 1970;19(2):61-70. [Medline].
Hensley ML, Maki R, Venkatraman E, et al. Gemcitabine and docetaxel in patients with unresectable leiomyosarcoma: results of a phase II trial. J Clin Oncol. Jun 15 2002;20(12):2824-31. [Medline].
International Federation of Gynecology and Obstetrics. Annual report on the results of treatment in gynecologic cancer. Int J Gynecol Obstet. 1989;28:189.
Jemal A, Murray T, Ward E, et al. Cancer statistics, 2005. CA Cancer J Clin. Jan-Feb 2005;55(1):10-30. [Medline].
Kauppila A. Progestin therapy of endometrial, breast and ovarian carcinoma. A review of clinical observations. Acta Obstet Gynecol Scand. 1984;63(5):441-50. [Medline].
Kempson RL, Bari W. Uterine sarcomas. Classification, diagnosis, and prognosis. Hum Pathol. Sep 1970;1(3):331-49. [Medline].
Kurman RJ, Kaminski PF, Norris HJ. The behavior of endometrial hyperplasia. A long-term study of "untreated" hyperplasia in 170 patients. Cancer. Jul 15 1985;56(2):403-12. [Medline].
Lehoczky O, Bosze P, Ungar L, Tottossy B. Stage I endometrial carcinoma: treatment of nonoperable patients with intracavitary radiation therapy alone. Gynecol Oncol. Dec 1991;43(3):211-6. [Medline].
Leibsohn S, d'Ablaing G, Mishell DR Jr, Schlaerth JB. Leiomyosarcoma in a series of hysterectomies performed for presumed uterine leiomyomas. Am J Obstet Gynecol. Apr 1990;162(4):968-74; discussion 974-6. [Medline].
Liu JH. American College of Obstetricians and Gynecologists: Hormone Replacement Therapy. Educational Bulletin # 247.
Loeffler JS, Rosen EM, Niloff JM, Howes AE, Knapp RC. Whole abdominal irradiation for tumors of the uterine corpus. Cancer. Apr 1 1988;61(7):1332-5. [Medline].
Mackillop WJ, Pringle JF. Stage III endometrial carcinoma. A review of 90 cases. Cancer. Nov 15 1985;56(10):2519-23. [Medline].
Major FJ, Blessing JA, Silverberg SG, et al. Prognostic factors in early-stage uterine sarcoma. A Gynecologic Oncology Group study. Cancer. Feb 15 1993;71(4 Suppl):1702-9. [Medline].
Mariani A, Webb MJ, Keeney GL, Aletti G, Podratz KC. Assessment of prognostic factors in stage IIIA endometrial cancer. Gynecol Oncol. Jul 2002;86(1):38-44. [Medline].
Massi G, Savino L, Susini T. Vaginal hysterectomy versus abdominal hysterectomy for the treatment of stage I endometrial adenocarcinoma. Am J Obstet Gynecol. Apr 1996;174(4):1320-6. [Medline].
Milosevic MF, Dembo AJ, Thomas GM. The clinical significance of malignant peritoneal cytology in stage I endometrial carcinoma. Int J Gynecol Cancer. Sep 1992;2(5):225-235. [Medline].
Moore DH, Fowler WC Jr, Walton LA, Droegemueller W. Morbidity of lymph node sampling in cancers of the uterine corpus and cervix. Obstet Gynecol. Aug 1989;74(2):180-4. [Medline].
Moore TD, Phillips PH, Nerenstone SR, Cheson BD. Systemic treatment of advanced and recurrent endometrial carcinoma: current status and future directions. J Clin Oncol. Jun 1991;9(6):1071-88. [Medline].
Omura GA, Blessing JA, Major F, et al. A randomized clinical trial of adjuvant adriamycin in uterine sarcomas: a Gynecologic Oncology Group Study. J Clin Oncol. Sep 1985;3(9):1240-5. [Medline].
Orr JW Jr, Holloway RW, Orr PF, Holimon JL. Surgical staging of uterine cancer: an analysis of perioperative morbidity. Gynecol Oncol. Sep 1991;42(3):209-16. [Medline].
Parazzini F, La Vecchia C, Bocciolone L, Franceschi S. The epidemiology of endometrial cancer. Gynecol Oncol. Apr 1991;41(1):1-16. [Medline].
Peters WA 3rd, Andersen WA, Thornton WN Jr, Morley GW. The selective use of vaginal hysterectomy in the management of adenocarcinoma of the endometrium. Am J Obstet Gynecol. Jun 1 1983;146(3):285-9. [Medline].
Quinn MA, Campbell JJ. Tamoxifen therapy in advanced/recurrent endometrial carcinoma. Gynecol Oncol. Jan 1989;32(1):1-3. [Medline].
Reddoch JM, Burke TW, Morris M, Tornos C, Levenback C, Gershenson DM. Surveillance for recurrent endometrial carcinoma: development of a follow-up scheme. Gynecol Oncol. Nov 1995;59(2):221-5. [Medline].
Runowicz CD, Nuchtern LM, Braunstein JD, Jones JG. Heterogeneity in hormone receptor status in primary and metastatic endometrial cancer. Gynecol Oncol. Sep 1990;38(3):437-41. [Medline].
Schwartz SM, Weiss NS, Daling JR, et al. Incidence of histologic types of uterine sarcoma in relation to menstrual and reproductive history. Int J Cancer. Sep 30 1991;49(3):362-7. [Medline].
Silverberg SG, Major FJ, Blessing JA, et al. Carcinosarcoma (malignant mixed mesodermal tumor) of the uterus. A Gynecologic Oncology Group pathologic study of 203 cases. Int J Gynecol Pathol. 1990;9(1):1-19. [Medline].
Soper JT, Creasman WT, Clarke-Pearson DL, Sullivan DC, Vergadoro F, Johnston WW. Intraperitoneal chromic phosphate P 32 suspension therapy of malignant peritoneal cytology in endometrial carcinoma. Am J Obstet Gynecol. Sep 15 1985;153(2):191-6. [Medline].
Further Reading
Keywords
uterine cancer, uterus, endometrial cancer, postmenopausal vaginal bleeding, signs, symptoms, treatment, adenocarcinoma, adenosquamous carcinoma, cancer of the uterus, clear cell carcinoma, uterine papillary serous carcinoma, UPSC, leiomyosarcoma, uterine sarcoma, MMT, mixed mullerian tumors, endometrial stromal sarcoma, carcinosarcoma
