Endometrial cancer develops in the lining of uterus. Uterus is a hollow organ present in the female body to which placenta attaches during pregnancy. The lining of uterus is constantly regenerating till the menopause is achieved. It is most common in postmenopausal women but can develop in premenopausal women also. Endometrial carcinoma is primarily a disease of menopausal and postmenopausal women with the peak incidence in women aged 55-65 years. Approximately 75% of patients are aged 50 years and older, and 5% are younger than 40 years. Endometrial carcinoma is rare in patients younger than age 30 years. Usually these cancer are detected in early stage and thus prognosis is good. Worldwide this is the most common malignancy in women while in India it occupies third place after cervix and breast.
Multiple risk factors are associated with endometrial cancer.
1. Disorders of menstruation
2. Increased Perimenopausal bleeding
3. Menopause after than age 52 years
4. Long time period between menarche and menopause
5. Estrogen replacement therapy
6. Tamoxifen therapy for breast cancer
7. Endometrial hyperplasia
10. Diabetes mellitus
12. Family history of endometrial or breast cancer.
13. Personal history of ovarian or breast cancer.
Extended estrogen exposure unopposed by progesterone is the main factor contributing to the development of this malignancy. All the conditions mentioned in the risk factors directly or indirectly give rise to prolonged estrogen exposure. Disease spread initially within the uterus followed by lymphatic spread to the lymph nodes in the pelvis and higher up in the abdomen. Locally it can grow outside the pelvis involving the adjacent organs like rectum, bladder or intestines. In the later stage it can spread via blood stream to lungs and in decreasing frequency, to the liver, brain or bones. If the depth of penetration in the uterus wall is in the mymetrium then the prognosis is bad compared to the women without myometrial involvement. These patients are more prone to have nodal involvement and or distant metastases.
Endometroid Carcinoma: Most common (75% to 80%). They can be of three types well differentiated, moderately differentiated and poorly differentiated or undifferentiated along with three grades depending on architectural and cytological features. Tumors with Grade 3 and undifferentiated type has a worse prognosis.
Uterine serous papillary carcinoma comprises 5-10% of endometrial carcinomas, commonly arises in atrophic Endometrium. Incidence is more in older women when compared to Endometroid carcinoma. This type of carcinoma is aggressive with a predilection for early deep myometrial and vascular invasion that frequently is associated with early extrauterine spread and, in some patients, with transtubal peritoneal dissemination.
Most important point about this type is --- this is to be treated very aggressively and requires different approach from the regular endometroid carcinoma type. Please consult your doctor about the treatment options.
Other aggressive tumor include clear cell carcinoma (3- 5%) which needs special consideration while deciding management.
Postmenopausal vaginal bleeding (80%) is most common presentation. Purulent vaginal discharge is present in 10% of patients. Pain and pelvic pressure are the indication of locally advanced disease.
Chances that postmenopausal vaginal bleeding is because of cancer are 10 - 20% but this percentage increases with increasing age.
1. Endometrial biopsy
2. Endometrial Curettage
3. Ultrasonography (TAS and TVS)
4. Contrast Enhanced Computed Tomography
5. Magnetic Resonance Imaging
Kinkel et al provided clinical practice guidelines for staging based on a meta-analysis of the usefulness of MRI, CT, and US in imaging patients with endometrial cancer.
* Patients with grade 1 tumor, a clinically normal-sized uterus, and no clinical evidence of coexisting pelvic disease generally require no preoperative imaging because the risk for myometrial, cervical, or lymph node disease is low. If the clinical evaluation is inconclusive or coexisting pelvic disease is suggested, then US, CT, or MRI may be used for the initial imaging evaluation.
* In patients at risk for disease dissemination and lymph node involvement at presentation (because of tumor grade, histologic cell type, or clinical findings) CT or MRI of the abdomen and pelvis should be performed to determine the extent of tumor spread.
* Patients in whom cervical invasion is suggested clinically or in whom endocervical curettage was inconclusive benefit in particular from MRI, because MRI can depict cervical and myometrial invasion most accurately and is approximately equivalent to CT in detecting enlarged lymph nodes.
Staging of Endometrial Carcinoma
I Confined to the uterine corpus
IA Tumor limited to endometrium
IB Invasion of < 1/2 myometrium
IC Invasion of > 1/2 myometrium
II Involvement of the uterus and cervix but no extension outside the uterus
IIA Involvement of endocervical glands
IIB Invasion of cervical stroma
III Extension beyond the uterus but not beyond the true pelvis
IIIA Invasion of serosa, adnexa, or both and/or positive peritoneal cytologic results
IIIB Metastases to vagina
IIIC Metastases to pelvic or para-aortic lymph nodes or both
IV Involvement of the bladder or intestinal mucosa or distant metastases
IVA Invasion of the bladder, intestinal mucosa, or both
IVB Distant metastases, including to intra-abdominal or inguinal lymph nodes or both
* Based on staging established by the International Federation of Gynecology and Obstetrics (FIGO) and American Joint Committee on Cancer (AJCC), 1989, 1992, and 1997. Endometrial cancer is usually surgically staged.
For all but stage IVB, grade (G) indicates percentage of tumor with a nonsquamous or nonmorular solid growth pattern:
G1: ≤ 5%
G3: > 50%
Nuclear atypia excessive for the grade raises the grade of a G1 or G2 tumor by 1. In serous adenocarcinomas, clear cell adenocarcinomas, and squamous cell carcinomas, nuclear grading takes precedence. Adenocarcinomas with squamous differentiation are graded according to the nuclear grade of the glandular component.
Disease which is limited to the uterus and pelvis without spread to any other part of the body is treated with surgery in first place. Surgery should be done by surgical oncologist. Post surgery adjuvant treatment depends on the factors which are seen on the detailed histopathology report of the specimen removed in the surgery. Broadly post surgery patient can be divided into 3 groups.
1. Low risk Endometrial cancer
2. Intermediate risk Endometrial cancer
3. High risk Endometrial cancer
Treatment of Low risk Endometrial cancer (please consult your oncologist regarding your risk group)
Low-risk endometrial cancer is defined as having all the following criteria:
* Low or intermediate grade cancer that is confined to the top of the uterus (called the fundus) with little or no invasion into the uterine muscle (stage I grade 1 or 2)
* No evidence of cancer cells in the surrounding lymph nodes or blood vessels
Surgery alone is enough and no further adjuvant treatment is required. Follow up is must and patient should continue to follow up with his doctor.
Treatment of Intermediate risk Endometrial cancer.(please consult your oncologist regarding your risk group)
Intermediate-risk endometrial cancer is defined as having the following criteria:
* A deeply invasive tumor (stage IC) or tumor that has limited cervix involvement (stage IIA) or a high-grade cancer with little or no invasion into the uterine muscle (stage IA/IB grade 3)
* No evidence of cancer in the surrounding lymph nodes or blood vessels.
* No evidence of metastasis outside of the uterus.
You may require no further treatment or need adjuvant treatment in the form of External beam radiotherapy or Brachytherapy or both. Best approach is to consult your oncologist regarding the need for adjuvant treatment and options of adjuvant treatment.
Treatment of high risk Endometrial cancer. (please consult your oncologist regarding your risk group)
High-risk endometrial cancer is defined as having one or more of the following criteria:
* High-grade tumor with deep invasion of the uterine muscle (stage1C grade 3 or involvement of the cervix (stage II)
* Spread of tumor outside of the uterus
* Evidence of cancer in the surrounding lymph nodes or blood vessels
* The cell type is a clear cell or papillary serous cancer.
Adjuvant radiation is always required if tumor is confined to the uterus and pelvis. Chemotherapy plays a additional important role in clear cell histology or papillary serous cancer. Please consult your doctor for the treatment options which suits you best.