Endometrial Cancer

Risk factors for endometrial cancer are

Increased exposure to extrinsic or intrinsic estrogen may be associated with

Most endometrial cancer is caused by sporadic mutations. However, in about 5% of patients, inherited mutations cause endometrial cancer; endometrial cancer due to inherited mutations tends to occur at a younger age and is often diagnosed 10 to 20 years earlier than sporadic cancer. About half of cases that involve heredity occur in families with Lynch syndrome (hereditary nonpolyposis colorectal cancer (HNPCC]). Patients who have Lynch syndrome have a high risk of developing other cancers (eg, colorectal cancer Colorectal Cancer Colorectal cancer is extremely common. Symptoms include blood in the stool and change in bowel habits. Screening using one of several methods is recommended for appropriate populations. Diagnosis... read more , ovarian cancer Ovarian, Fallopian Tube, and Peritoneal Cancer Ovarian cancer is often fatal because it is usually advanced when diagnosed. The most common histology—high-grade serous epithelial ovarian cancer—is considered as a single clinical entity along... read more ).

Endometrial cancer is usually preceded by endometrial hyperplasia. Endometrial carcinoma is commonly classified into 2 types.

Type I tumors are more common, are usually estrogen-responsive, and are usually diagnosed in obese women and at younger ages (perimenopause or early in menopause). They are preceded by endometrial hyperplasia. These tumors are usually low-grade; the prognosis is good. Endometrioid adenocarcinoma (grades 1 and 2) is the most common histology. These tumors may show microsatellite instability and have mutations in PTEN, PIK3CA, KRAS, and CTNNB1.

Type II tumors are usually high-grade and include grade 3 endometrioid carcinomas and tumors with nonendometrioid histology (eg, serous, clear cell, mixed cell, undifferentiated, carcinosarcoma). They tend to occur in older women. About 10 to 30% have p53 mutations. Up to 10% of endometrial carcinomas are type II. The prognosis is poor.

Endometrioid adenocarcinomas account for about 75 to 80% of endometrial cancers.

Uterine papillary serous carcinomas (10%), clear cell carcinomas (< 5%), and carcinosarcomas (< 5%) are considered more aggressive, high-risk histologies and are associated with a higher incidence of extrauterine disease at presentation. Carcinosarcomas used to be categorized as sarcomas but are now considered and treated as high-grade epithelial tumors (carcinomas).

Mucinous carcinomas are typically low-grade; the prognosis is good. KRAS mutations are common in these tumors.

Other histopathologic types of endometrial carcinoma are neuroendocrine, undifferentiated, and mixed carcinoma (composed of more than one type, with at least 10% of each component).

Endometrial cancer may spread as follows:

The higher (more undifferentiated) the grade of the tumor, the greater the likelihood of deep myometrial invasion, pelvic or para-aortic lymph node metastases, or extrauterine spread.

Most (> 90%) women with endometrial cancer have abnormal uterine bleeding (eg, postmenopausal bleeding, premenopausal intermenstrual bleeding, ovulatory dysfunction). Depending on age and risk factors, 1 to 14% of women with postmenopausal bleeding have endometrial cancer.

The following suggest endometrial cancer:

If endometrial cancer is suspected, outpatient endometrial biopsy is done; sensitivity is > 90%. An alternative for average-risk postmenopausal women is transvaginal ultrasonography (1 Diagnosis references Endometrial cancer is usually endometrioid adenocarcinoma. Typically, it manifests as postmenopausal uterine bleeding. Diagnosis is by biopsy. Staging is surgical. Treatment requires hysterectomy... read more ); biopsy is required if endometrial lining thickness is > 4 mm and results are inconclusive.

If biopsy results are inconclusive or suggest precancer (eg, complex hyperplasia with atypia) or cancer, dilation and curettage (D & C), often with hysteroscopy, is done.

Once endometrial cancer is diagnosed, pretreatment evaluation includes a complete blood count (CBC) and other blood tests (serum electrolytes, kidney, and liver). A chest x-ray is done. If an abnormality is seen on chest x-ray, CT should be done. The following should be considered:

Because endometrial cancer sometimes results from an inherited mutation, genetic counseling and/or testing should be considered if patients are < 50 years or have a significant family history of endometrial cancer, ovarian cancer, or colorectal cancer or known Lynch syndrome (HNPCC).

Prognosis is worse with higher-grade tumors, more extensive spread, and older patient age.

Average 5-year survival rates for patients with endometrial cancer are

Overall, 63% of patients are cancer-free ≥ 5 years after treatment.

(See also National Comprehensive Cancer Network (NCCN): NCCN Clinical Practice Guidelines in Oncology: Uterine Neoplasms.)

Endometrial cancer should be removed en bloc, usually by doing a total hysterectomy and bilateral salpingo-oophorectomy. Intraperitoneal tumor fragmentation or morcellation must be avoided.

Surgery can be done by any route (vaginal, open, robotic, laparoscopic). For patients with tumors confined to the uterus, minimally invasive surgery is the preferred approach because its rate of perioperative and postoperative complications is lower, hospital stays are shorter (1 Treatment references Endometrial cancer is usually endometrioid adenocarcinoma. Typically, it manifests as postmenopausal uterine bleeding. Diagnosis is by biopsy. Staging is surgical. Treatment requires hysterectomy... read more ), cost is lower, and oncologic outcomes are comparable (2 Treatment references Endometrial cancer is usually endometrioid adenocarcinoma. Typically, it manifests as postmenopausal uterine bleeding. Diagnosis is by biopsy. Staging is surgical. Treatment requires hysterectomy... read more ).

Evidence generally supports comparable oncologic outcomes for laparoscopic surgery and laparotomy. In the Gynecologic Oncology Group LAP2 study, women with clinical stage I to IIA uterine cancer were randomly assigned to have laparoscopic surgery or laparotomy in a 2 to 1 ratio. The study did not demonstrate the statistical noninferiority of the laparoscopic approach. However, after a median follow-up time of 59 months, survival rates for both approaches were similar; 5-year overall survival rate was 90% in both groups. Estimated 5-year recurrence rates were also similar (14% versus 12% [ 3 Treatment references Endometrial cancer is usually endometrioid adenocarcinoma. Typically, it manifests as postmenopausal uterine bleeding. Diagnosis is by biopsy. Staging is surgical. Treatment requires hysterectomy... read more ]). The Laparoscopic Approach to Cancer of the Endometrium (LACE) trial was a prospective, international, randomized trial that included 760 patients with stage I endometrioid uterine cancer. They were randomly assigned to have laparoscopic hysterectomy or open hysterectomy. Disease-free survival at 4.5 years (82% versus 81%) and overall survival (mortality: 7.4% versus 6.8%) were similar (4 Treatment references Endometrial cancer is usually endometrioid adenocarcinoma. Typically, it manifests as postmenopausal uterine bleeding. Diagnosis is by biopsy. Staging is surgical. Treatment requires hysterectomy... read more ).

In patients with grade 1 or 2 endometrial cancer and < 50% invasion, the probability of lymph node metastasis is < 2%. In these patients, treatment is usually total hysterectomy and bilateral salpingo-oophorectomy via laparotomy, laparoscopy, or robotic-assisted surgery. However, for young women with stage IA or IB endometrioid adenocarcinoma, ovarian preservation is usually safe and recommended to preserve ovarian function.

If patients have any of the following, pelvic and para-aortic lymphadenectomy is also done (unless SLN mapping Sentinel lymph node mapping in endometrial cancer Endometrial cancer is usually endometrioid adenocarcinoma. Typically, it manifests as postmenopausal uterine bleeding. Diagnosis is by biopsy. Staging is surgical. Treatment requires hysterectomy... read more identified bilateral SLNs):

If SLNs are identified bilaterally, no lymphadenectomy is indicated, regardless of tumor characteristics. If a sentinel node is not identified on one side, complete lymphadenectomy is necessary on that side.

Stage II or III endometrial cancer requires pelvic radiation therapy with or without chemotherapy. Treatment of stage III cancer must be individualized, but surgery is an option; generally, patients who have combined surgery and radiation therapy have a better prognosis. Except in patients with bulky parametrial disease, a total abdominal hysterectomy and bilateral salpingo-oophorectomy should be done.

Treatment of stage IV endometrial cancer is variable and patient-dependent but typically involves a combination of surgery, radiation therapy, and chemotherapy. Occasionally, endocrine therapy should also be considered.

Tumors respond to endocrine therapy with a progestin in 20 to 25% of patients.

Several cytotoxic drugs (particularly carboplatin plus paclitaxel) are effective. They are given mainly to women with metastatic or recurrent cancer. Another option is doxorubicin.

For advanced cancer, chemotherapy with carboplatin and paclitaxel has been the standard. However, recent data support the use of lenvatinib, a multitargeted tyrosine kinase inhibitor of VEGF (vascular endothelial growth factor) receptors, and pembrolizumab, a monoclonal antibody that inhibits programmed cell death-1 (PD-1) activity. A recent phase II trial showed an objective response rate of 39.6% in patients taking this combination (5 Treatment references Endometrial cancer is usually endometrioid adenocarcinoma. Typically, it manifests as postmenopausal uterine bleeding. Diagnosis is by biopsy. Staging is surgical. Treatment requires hysterectomy... read more ).

The following is an English-language resource that may be useful. Please note that THE MANUAL is not responsible for the content of this resource.