Endometrial cancer

Endometrial cancer begins in the layer of cells that form the lining (the endometrium) of the uterus (see Figures 1 and 3). The uterus is part of the female reproductive system. It is a hollow, pear-shaped, muscular organ in the pelvis, where a fetus grows. Endometrial cancer is often detected at an early stage, because it frequently produces abnormal vaginal bleeding such as vaginal bleeding after menopause or bleeding between periods, which prompts women to see their health care providers. If endometrial cancer is discovered early, removing the uterus surgically often cures endometrial cancer.

Endometrial cancer is the fourth most common cancer in women in the United States after breast, lung, and colorectal cancers ¹.

In the United States, cancer of the endometrium (the lining of the uterus) is the most common cancer of the female reproductive organs. The American Cancer Society estimates for cancer of the uterus in the United States for 2023 are ², ³:

• New cases: About 66,200 new cases of cancer of the body of the uterus (uterine body or corpus) will be diagnosed.
• Deaths: About 13,030 women will die from cancers of the uterine body.
• 5-Year Relative Survival: 81.3%. Relative survival is an estimate of the percentage of patients who would be expected to survive the effects of their cancer. It excludes the risk of dying from other causes. Because survival statistics are based on large groups of people, they cannot be used to predict exactly what will happen to an individual patient. No two patients are entirely alike, and treatment and responses to treatment can vary greatly.
• Endometrial cancer deaths as a percentage of All Cancer Deaths: 2.1%.
• Rate of New Cases and Deaths per 100,000: The rate of new cases of uterine cancer was 27.8 per 100,000 women per year. The death rate was 5.0 per 100,000 women per year. These rates are age-adjusted and based on 2015–2019 cases and deaths.
• Lifetime Risk of Developing Cancer: Approximately 3.1 percent of women will be diagnosed with uterine cancer at some point during their lifetime, based on 2017–2019 data.
• In 2019, there were an estimated 822,388 women living with uterine cancer in the United States. There are more than 600,000 survivors of endometrial cancer in the US today.

These estimates include both endometrial cancers and uterine sarcomas. Up to 10% of uterine body cancers are sarcomas, so the actual numbers for endometrial cancer cases and deaths are slightly lower than these estimates.

Endometrial cancer affects mainly post-menopausal women. The average age of women diagnosed with endometrial cancer is 60. It’s uncommon in women under the age of 45.

Endometrial cancer is more common in Black women than white women, and Black women are more likely to die from it.

Endometrial cancer is often detected at an early stage because it frequently produces abnormal vaginal bleeding. If endometrial cancer is discovered early, removing the uterus surgically often cures endometrial cancer.

Your particular treatment plan depends on the type of cancer and your overall health. Treatment for endometrial cancer is usually with surgery to remove the uterus, fallopian tubes and ovaries. Another option is radiation therapy with powerful radiation energy. Drug treatments for endometrial cancer include chemotherapy with powerful drugs and hormone therapy to block hormones that cancer cells rely on. Other options might be targeted therapy with drugs that attack specific weaknesses in the cancer cells and immunotherapy to help your immune system fight cancer.

Are endometrial cancer and uterine cancer the same?

Uterine cancer can refer to either endometrial cancer, uterine sarcoma or other rare forms of cancer that can arise in your uterus (womb). But people often treat the terms “endometrial cancer” and “uterine cancer” the same. That’s because endometrial cancers are much more common than other cancers that can form in your uterus. Uterine sarcomas are very rare. Uterine sarcoma develops in the myometrium, the muscle wall of your uterus.

Uterus and endometrium

The uterus is a hollow, muscular organ shaped somewhat like an inverted pear. The uterus receives the embryo that develops from an oocyte fertilized in the uterine tube, and sustains its development.

In its nonpregnant, adult state, the uterus is about 7 centimeters long, 5 centimeters wide (at its broadest point), and 2.5 centimeters in diameter. The size of the uterus changes greatly during pregnancy and it is somewhat larger in women who have been pregnant. The uterus is located medially in the anterior part of the pelvic cavity, superior to the vagina, and usually bends forward over the urinary bladder (see Figure 3).

The uterus has 2 main parts:

• The upper part of the uterus is called the body or the corpus. Corpus is the Latin word for body.
• The cervix is the lower end of the uterus that joins it to the vagina.

When people talk about cancer of the uterus, they usually mean cancers that start in the body of the uterus, not the cervix. Cervical cancer is a separate kind of cancer.

The upper two-thirds or body (corpus), of the uterus has a domeshaped top called the fundus (see Figure 1). The uterine tubes (also called Fallopian tubes) connect at the upper lateral edges of the uterus. The lower third of the uterus is called the cervix. This tubular part extends downward into the upper part of the vagina. The cervix surrounds the opening called the cervical orifice, through which the uterus opens to the vagina.

The uterine wall is thick and has 3 layers (Figure 1):

• The endometrium, the inner mucosal layer, is covered with columnar epithelium and contains abundant tubular glands (see Figure 3). During a woman’s menstrual cycle, hormones cause the endometrium to change. Estrogen causes the endometrium to thicken so that it could nourish an embryo if pregnancy occurs. If there is no pregnancy, estrogen is produced in lower amounts and more of the hormone called progesterone is made. This causes the endometrial lining to shed from the uterus and become the menstrual flow (period). This cycle repeats until menopause.
• The myometrium, a thick, middle, muscular layer, consists largely of bundles of smooth muscle cells. This thick layer of muscle is needed to push the baby out during birth. During the monthly female menstrual cycles and during pregnancy, the endometrium and myometrium change extensively.
• The perimetrium also called the serosa consists of an outer serosal layer, which covers the body of the uterus and part of the cervix.

During a woman’s menstrual cycle, hormones cause the endometrium to change. During the early part of the cycle, before the ovaries release an egg (ovulation), the ovaries produce hormones called estrogens. Estrogen causes the endometrium to thicken so that it could nourish an embryo if pregnancy occurs. If there is no pregnancy, estrogen is produced in lower amounts and more of the hormone called progesterone is made after ovulation. This prepares the innermost layer of the lining to shed. By the end of the cycle, the endometrial lining is shed from the uterus and becomes the menstrual flow (period). This cycle repeats until the woman’s goes through menopause (change of life).

The uterus is supported by the muscular floor of the pelvis and folds of peritoneum that form supportive ligaments around the organ, as they do for the ovary and uterine tube. The broad ligament has two parts: the mesosalpinx mentioned earlier and the mesometrium on each side of the uterus. The cervix and superior part of the vagina are supported by cardinal (lateral cervical) ligaments extending to the pelvic wall. A pair of uterosacral ligaments attaches the posterior side of the uterus to the sacrum, and a pair of round ligaments arises from the anterior surface of the uterus, passes through the inguinal canals, and terminates in the labia majora.

As the peritoneum folds around the various pelvic organs, it creates several dead-end recesses and pouches (extensions of the peritoneal cavity). Two major ones are the vesicouterine pouch, which forms the space between the uterus and urinary bladder, and rectouterine pouch between the uterus and rectum (see Figure 2).

The uterine blood supply to the uterus is particularly important to the menstrual cycle and pregnancy. A uterine artery arises from each internal iliac artery and travels through the broad ligament to the uterus (Figure 4). It gives off several branches that penetrate into the myometrium and lead to arcuate arteries. Each arcuate artery travels in a circle around the uterus and anastomoses with the arcuate artery on the other side. Along its course, it gives rise to smaller arteries that penetrate the rest of the way through the myometrium, into the endometrium, and give off spiral arteries. The spiral arteries wind tortuously between the endometrial glands toward the surface of the mucosa. They rhythmically constrict and dilate, making the mucosa alternately blanch and flush with blood.

Figure 1. Uterus

Figure 2. Uterus location

Figure 3. Endometrium of the uterus and its blood supply

Figure 4. Blood supply to the uterus

Endometrium function

The endometrium changes throughout the menstrual cycle in response to hormones. During the first part of the cycle, the hormone estrogen is made by the ovaries. Estrogen causes the lining to grow and thicken to prepare the uterus for pregnancy. In the middle of the cycle, an egg is released from one of the ovaries (ovulation).

Following ovulation, levels of another hormone called progesterone begin to increase. Progesterone prepares the endometrium to receive and nourish a fertilized egg. If pregnancy does not occur, estrogen and progesterone levels decrease. The decrease in progesterone triggers menstruation, or shedding of the lining. Once the lining is completely shed, a new menstrual cycle begins.

Figure 5. Ovarian activity during the Menstrual cycle

Footnote: Major events in the female menstrual cycle. (a) Plasma hormonal concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) affect follicle maturation in the ovaries. (b) Plasma hormonal concentrations of estrogen and progesterone influence changes in the uterine lining.

Endometrial hyperplasia

Endometrial hyperplasia is a common condition in which the endometrium (lining of the uterus) is abnormally thick. The uterus is part of the female reproductive system. It is a hollow, pear-shaped, muscular organ in the pelvis, where a fetus grows. Endometrial hyperplasia is defined as a proliferation of endometrial glands of irregular size and shape that results in a greater than normal gland-to-stroma ratio ⁴. Endometrial hyperplasia is caused by too much exposure to exogenous or endogenous estrogen along with a relative deficiency of progesterone ⁵. Both estrogen and progesterone hormones play roles in the menstrual cycle. Estrogen makes the cells grow, while progesterone signals the shedding of the cells. A hormonal imbalance estrogen and progesterone hormones in can produce too many cells or abnormal cells. Endometrial hyperplasia is not cancer, but in some cases, if it’s not treated, has the propensity to develop into endometrial cancer or cancer of the uterus ⁶. Endometrial hyperplasia is believed to be a precursor of cancer of the uterus or endometrial carcinoma, which is the most common gynecologic cancer and the fourth most common cancer in women in the United States ⁷.

Endometrial hyperplasia is most frequently diagnosed in postmenopausal women, but women of any age can be at risk if they are exposed to a source of unopposed estrogen ⁸. Endometrial hyperplasia is increasingly seen in young women with chronic anovulation due to polycystic ovary syndrome (PCOS) or obesity ⁹.

Endometrial hyperplasia usually occurs after menopause, when ovulation stops and progesterone is no longer made ¹⁰. Endometrial hyperplasia can also develop during perimenopause, when ovulation may not occur regularly. There may be high levels of estrogen and not enough progesterone in other situations, including when a woman ¹⁰:

• uses medications that act like estrogen, such as tamoxifen for cancer treatment
• uses estrogen for hormone therapy and does not use progesterone or progestin if she still has a uterus
• has irregular menstrual periods, especially associated with polycystic ovary syndrome (PCOS) or infertility
• has obesity – body mass index (BMI) of 27 or more

The main symptom of endometrial hyperplasia is abnormal menstrual bleeding. However, abnormal uterine bleeding can be a symptom for many things. Your doctor can perform an exam and tests to diagnose the cause of the abnormal uterine bleeding. A transvaginal ultrasound measures your endometrium. It uses sound waves to see if the layer is average or too thick. A thick layer can indicate endometrial hyperplasia. Endometrial hyperplasia is typically diagnosed by endometrial biopsy or curettage when a woman is noted as suffering from abnormal uterine bleeding ¹¹. Your doctor will take a biopsy of your endometrium cells to determine if cancer is present.

Treatment options for endometrial hyperplasia depend on what type you have. The most common treatment is progestin. This can be taken in several forms, including pill, shot, vaginal cream, or intrauterine device.

Atypical types of endometrial hyperplasia, especially complex, increase your risk of getting cancer. If you have these types, you might consider a hysterectomy. This is a surgery to remove your uterus. Doctors recommend this if you no longer want to become pregnant.

There are also a number of more conservative treatments for younger women who do not wish to have a hysterectomy. Your doctor will help you decide which treatment option is best for you.

Figure 6. Endometrial hyperplasia ultrasound

Footnote: Endometrial thickness is 12 mm. Multiple cystic spaces are noted within. Solid areas are echogenic. Margins of endometrial lining was well-defined. No significant flow signals seen. Myometrium does not show focal lesion. Either of ovaries could not be localized.

[Source ¹² ]

Types of endometrial hyperplasia

The types of endometrial hyperplasia vary by the amount of abnormal cells and the presence of cell changes. According to the World Health Organization endometrial hyperplasia classification system in 1994 (WHO94), endometrial hyperplasia can be divided into 4 categories ¹³:

1. Simple endometrial hyperplasia – Increased number of endometrial glands but regular glandular architecture.
2. Complex endometrial hyperplasia – Crowded irregular endometrial glands.
3. Simple atypical endometrial hyperplasia – Simple hyperplasia with presence of cytologic atypia (prominent nucleoli and nuclear pleomorphism).
4. Complex atypical endometrial hyperplasia – Complex hyperplasia with cytologic atypia

The World Health Organization endometrial hyperplasia classification system 1994 (WHO94) was based on the original retrospective study of 170 patients by Kurman et al ¹³ who found that lesions with varying degrees of complexity and presence of atypia, when left untreated for a mean of 13 years, progressed to adenocarcinoma at different rates. Simple endometrial hyperplasia was associated with a 1% rate of progression to cancer, complex endometrial hyperplasia 3% rate of progression, simple atypical endometrial hyperplasia 8% rate of progression, whereas complex atypical endometrial hyperplasia had a 29% rate of progression to cancer ¹³.

Not only does the concern exist for atypical endometrial hyperplasia progressing to invasive cancer if untreated, but numerous studies found coexisting carcinoma at rates ranging from 17-56% ¹¹, ¹⁴. A prospective Gynecologic Oncology Group study found that 306 patients with preoperative biopsies that diagnosed atypical endometrial hyperplasia had concurrent invasive adenocarcinoma in 42.6% of hysterectomy specimen ¹⁵. Part of the difficulty in diagnosing concurrent carcinoma is due to lack of reproducibility in diagnosing hyperplasia, especially atypical hyperplasia versus adenocarcinoma among even expert gynecologic pathologists. Studies report only 40-69% interobserver agreement for endometrial hyperplasia or endometrial cancer ¹⁶.

Due to the poor reproducibility of diagnosis, and confusion regarding optimal clinical management, gynecologic pathologists proposed a simpler classification of endometrial hyperplasia versus endometrial intraepithelial neoplasia (EIN) using a computerized morphometric analysis. Endometrial hyperplasia is benign hyperplasia and correlates closely to simple hyperplasia, whereas endometrial intraepithelial neoplasia (EIN) is a pre-malignant condition ¹⁷. Endometrial intraepithelial neoplasia (EIN) is defined as when the volume of glandular crowding is greater than the stromal volume, the presence of cytologic alterations, a lesion larger than 1 mm, and exclusion of mimics or carcinoma ¹⁷. Classification as complex atypical hyperplasia (WHO’94) or as endometrial intraepithelial neoplasia (EIN) had similar sensitivities and negative predictive values for coexisting endometrial cancer ¹⁸. Others found the endometrial intraepithelial neoplasia (EIN) classification to be better at predicting progression to cancer. Thus in 2014 the WHO formally adopted the simplified classification of endometrial hyperplasia into 2 categories.

World Health Organization endometrial hyperplasia classification system in 2014 (Table 1) ¹⁹:

1. Hyperplasia without atypia or benign endometrial hyperplasia. Hyperplasias without atypia (benign endometrial hyperplasia) exhibit no relevant genetic changes. They are benign changes and will regress again after the endocrine milieu (physiological gestagen levels) has normalized. In a few cases (1–3 %), progression to invasive disease may occur if the endocrine disorder (long-term estrogen dominance or relative or absolute gestagen deficiency) persists over the long term.
   
2. Endometrial Intraepithelial Neoplasia (EIN) or atypical endometrial hyperplasia. Atypical endometrial hyperplasias exhibit many of the mutations typical for invasive endometrioid endometrial cancer ²⁰. In up to 60 % of cases, patients have coexisting invasive cancer or are at extremely high risk of developing invasive cancer (see Table 1).
   

This reduction to 2 categories was not only due to the need to do away with the confusing multitude of terms currently in use. Rather, it reflects a new understanding of molecular genetic changes.

The American College of Obstetricians and Gynecologists and the Society of Gynecologic Oncology Committee opinion 2015 also recommend the use of endometrial intraepithelial neoplasia (EIN) schema for a more clear terminology to distinguish the two clinicopathologic categories ⁷, ²¹. ​ Not only does this classification reflect clinical outcome, but also underlying genetic and molecular changes ²².

The implications for treatment are obvious: hyperplasias without atypia should generally be treated conservatively (normalization of the cycle through weight loss, metformin; oral contraceptives; cyclical gestagens; gestagen IUD). Preventive hysterectomy should only be considered in exceptional cases (e.g., extreme obesity without any prospect of weight loss) ²³. The surgery should be done as a total hysterectomy, i.e., it must include removal of the cervix ²³.

Treatment of atypical hyperplasia or endometrioid intraepithelial neoplasia should generally consist of total (not supracervical) hysterectomy ²³. Conservative treatment with high-dose gestagens and close histological monitoring should only be considered in exceptional cases (when the patient wants to have children, satisfactory compliance) ²⁴, ²³.

Table 1. New World Health Organization (WHO) classification of endometrial hyperplasia

New term	Synonyms	Genetic changes	Coexistent invasive endometrial carcinoma	Progression to invasive carcinoma
Hyperplasia without atypia	Benign endometrial hyperplasia; simple non-atypical endometrial hyperplasia; complex non-atypical endometrial hyperplasia; simple endometrial hyperplasia without atypia; complex endometrial hyperplasia without atypia	Low level of somatic mutations in scattered glands with morphology on HE staining showing no changes	< 1 %	RR: 1.01–1.03
Atypical hyperplasia or endometrioid intraepithelial neoplasia	Complex atypical endometrial hyperplasia; simple atypical endometrial hyperplasia; endometrial intraepithelial neoplasia (EIN)	Many of the genetic changes typical for endometrioid endometrial cancer are present, including: micro satellite instability; PAX2 inactivation; mutation of PTEN, KRAS and CTNNB1 (β-catenin)	25–33 % 19 59 % 25	RR: 14–45

Footnotes: RR = Relative Risk. Relative risk is a ratio of the probability of an event occurring in the exposed group versus the probability of the event occurring in the non-exposed group. Relative Risk = (Probability of event in exposed group) / (Probability of event in not exposed group) ²⁶. For example, atypical hyperplasia or endometrioid intraepithelial neoplasia (EIN) has a Relative Risk of 14 to 45 times more likely to progress to invasive endometrial cancer in this study compared to those without atypical hyperplasia or endometrioid intraepithelial neoplasia (EIN) in the study.

[Source ²² ]

Endometrial hyperplasia signs and symptoms

The most common of endometrial hyperplasia is abnormal menstrual bleeding. If you have any of the following, you should see your doctor or an obstetrician–gynecologist (ob-gyn):

• Menstrual bleeding that is heavier or longer lasting than usual.
• Menstrual cycles (amount of time between periods) that are shorter than 21 days (counting from the first day of the menstrual period to the first day of the next menstrual period).
• Menstrual bleeding between menstrual periods.
• Not having a period (pre-menopause).
• Any bleeding after menopause.

Endometrial hyperplasia causes

Endometrial hyperplasia is the result of chronic unopposed estrogenic stimulation of the endometrial tissue with a relative deficiency of the counterbalancing effects of progesterone ²⁷. The causes of estrogen excess could be endogenous or exogenous. For example, if ovulation does not occur, progesterone is not made, and the lining is not shed. The endometrium may continue to grow in response to estrogen. The cells that make up the lining may crowd together and may become abnormal. This condition, called hyperplasia, can lead to cancer.

You are more likely to have endometrial hyperplasia if you have gone through menopause. This is because your body’s hormones and menstrual cycles change. Other risk factors for endometrial hyperplasia are:

• Long-term use of medicines that contain high levels of estrogen or chemicals that act like estrogen.
• Irregular menstrual cycles, which can be caused by infertility or polycystic ovary syndrome (PCOS).
• Obesity.
• Use of tobacco.
• First menstrual cycle at an early age.
• Going through menopause at an older age.
• Never having been pregnant.
• Family history of uterine, ovarian, or colon cancer.

Endometrial hyperplasia pathology outlines

Endometrial hyperplasia is defined as a proliferation of endometrial glands of irregular size and shape that results in a greater than normal gland-to-stroma ratio ⁴. This results in varying degrees of architectural complexity and cytologic atypia.

Endometrial hyperplasia results from continuous estrogen stimulation that is unopposed by progesterone ²⁸. This can be due to endogenous estrogen or exogenous estrogenic sources. Endogenous estrogen may be caused by chronic anovulation associated with polycystic ovary syndrome (PCOS). Obesity also contributes to unopposed estrogen exposure due to chronic high levels of estradiol that result from aromatization of androgens in adipose tissue and conversion of androstenedione to estrone. Endometrial hyperplasia and cancer can also result from estradiol-secreting ovarian tumors such as granulosa cell tumors.

Exogenous unopposed estrogen without progesterone has been associated with increased endometrial hyperplasia and adenocarcinoma ²⁹. The Postmenopausal Estrogen/Progestin Interventions (PEPI) trial found that unopposed estrogen exposure with 0.625 mg of conjugated equine estrogen replacement therapy increased the risk of complex hyperplasia by 22.7% and atypical hyperplasia by 11.8% over 3 years of use compared with a less than 1% increase in placebo controls ³⁰. The risk of endometrial cancer was not increased when 2.5 mg of medroxyprogesterone acetate was used in combination with 0.625 mg of conjugated equine estrogens in 8506 women in the Women’s Health Initiative (WHI) study ³¹. Tamoxifen, with its estrogenic effect on the endometrium, increases the risk of endometrial hyperplasia and endometrial cancer. The risk of progression to cancer is associated with an increased duration of use ³². While unopposed estrogen in oral contraceptive pills or estrogen replacement therapy increases the risk of endometrial hyperplasia and endometrial cancer, combination oral contraceptive pills and combination hormone replacement therapy does not increase and may decrease the risk of endometrial hyperplasia and endometrial cancer ²⁸.

However, the exact mechanism of estrogen’s role in the transformation of normal endometrium to hyperplasia and cancer is unknown  ²⁸. Genetic alterations are known to be associated with hyperplasia and type 1 endometrial cancers. Benign endometrial hyperplasia is associated with low levels of somatic mutations, whereas EIN is associated with genetic alternations similar to endometrioid endometrial cancer such as microsatellite instability, and mutations in PTEN and KRAS ³³. PTEN tumor suppressor gene mutations have also been found in 55% of endometrial hyperplasia cases and 83% of endometrial hyperplasia cases once it has progressed to endometrial cancer ³⁴.

Endometrial hyperplasia risk factors

Endometrial hyperplasia is more likely to occur in women with risk factors, including ⁶:

• Age (age older than 53 years)
• Early age when menstruation started (early menarche [a girl’s first period])
• Late menopause (older age at menopause)
  
• Nulliparity (a woman who hasn’t given birth to a child or never having been pregnant)
• Obesity: body mass index (BMI) of 27 or more
• Genetic
• Cigarette smoking
• History of certain conditions, such as diabetes mellitus, gallbladder disease, or thyroid disease.
• Anovulatory cycles: polycystic ovary syndrome (PCOS), perimenopause
• Ovarian tumors: granulosa cell tumors
• Hormone replacement therapy: estrogen-only therapy can lead to endometrial hyperplasia at even a minimal dose and is contraindicated in women with a uterus. Over the counter/ herbal preparations may have a high amount of estrogen ³⁵
• Immunosuppression (renal graft recipients) and infection may also be involved in the development of endometrial hyperplasia ³⁶
• Hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome – women with this condition are at a greatly increased risk of endometrial hyperplasia ³⁷.
• Family history of ovarian, colon, or uterine cancer

The independent risk factors for predicting when endometrial hyperplasia coexists with cancer include age older than 53 years, postmenopausal status, diabetes, abnormal bleeding, body mass index (BMI) of 27 or more, and atypical hyperplasia ¹¹.

Endometrial hyperplasia prevention

You cannot prevent endometrial hyperplasia, but you can help lower your risk of endometrial hyperplasia by:

• Losing weight, if you are overweight or obese.
• Quit smoking if you smoke cigarette
• Taking a medicine with progestin (synthetic progesterone), if you already are taking estrogen, due to menopause or another condition.
• If your periods are irregular, birth control pills may be recommended. They contain estrogen along with progestin. Other forms of progestin also may be taken.
• Taking birth control or another medicine to regulate your hormones and menstrual cycle.

Endometrial hyperplasia differential diagnosis

The potential differential diagnosis for endometrial hyperplasia are conditions which can result in focal or generalized thickening of the endometrium ⁵:

• Endometrial cancer: Histopathological examination of the endometrial tissue can show markers of invasions in endometrial cancer.
• Endometrial polyp: Hydrosonography can be helpful in diagnosing endometrial polyp by enhancing visualization. Diagnostic hysteroscopy can confirm the presence of a polyp.
• Endometritis: Irregular endometrium and focal thickness are the hallmarks of endometritis.

Endometrial hyperplasia diagnosis

There are many causes of abnormal uterine bleeding. If you have abnormal bleeding and you are 35 or older, or if you are younger than 35 and your abnormal bleeding has not been helped by medication, your doctor may recommend diagnostic tests for endometrial hyperplasia and cancer.

A transvaginal ultrasound exam may be done to measure the thickness of the endometrium. For this test, a small device is placed in your vagina. Sound waves from the device are converted into images of the pelvic organs. If the endometrium is thick, it may mean that endometrial hyperplasia is present.

The only way to tell for certain that cancer is present is to take a small sample of tissue from the endometrium and study it under a microscope. This can be done with an endometrial biopsy, dilation and curettage (D&C), or hysteroscopy.

Endometrial hyperplasia ultrasound

Imaging the endometrium on days 5-10 of a woman’s cycle reduces the variability in endometrial thickness ³⁸.

• Premenopausal endometrial thickness
  • Normal endometrial thickness depends on the stage of the menstrual cycle, but a thickness of >15 mm is considered the upper limit of normal in the secretory phase
  • Endometrial hyperplasia can be reliably excluded in patients only when the endometrium measures less than 8 mm ³⁹
• Postmenopausal endometrial thickness of >5 mm is considered abnormal ³⁸.

The appearance can be non-specific and cannot reliably allow differentiation between endometrial hyperplasia and endometrial carcinoma ⁴⁰. Usually, there is a homogeneous smooth increase in endometrial thickness, but endometrial hyperplasia may also cause asymmetric/focal thickening with surface irregularity, an appearance that is suspicious for carcinoma. Cystic changes can also be seen in endometrial hyperplasia.

Ultrasound features that are suggestive of endometrial carcinoma as opposed to endometrial hyperplasia include ⁴¹:

• heterogeneous and irregular endometrial thickening
• polypoid mass lesion
• intrauterine fluid collection
• frank myometrial invasion

Endometrial hyperplasia biopsy

Diagnosis of endometrial hyperplasia is usually made by sampling the endometrial cavity with an endometrial biopsy in the office. Tissue sampling should be performed in women with risk factors who present with symptoms of abnormal vaginal bleeding or discharge ⁴². This includes women older than 35 years with abnormal bleeding, women younger than 35 years with bleeding and risk factors, women with persistent bleeding, and women with unopposed estrogen replacement, tamoxifen therapy, and hereditary nonpolyposis colorectal cancer (HNPCC) syndrome or Lynch syndrome.

In addition, a biopsy should be performed in women with atypical glandular cells Pap smear or endometrial cells in Pap smears of women older than 40 years when out of synch with menstrual cycle ⁴³. While no evidence of improved survival has been documented, some also advocate routine screening by endometrial biopsy in asymptomatic women with hereditary nonpolyposis colorectal cancer (HNPCC) syndrome or those on tamoxifen therapy. However, most of this high-risk population present with abnormal vaginal bleeding; thus, other experts recommend work-up only when symptoms are present.

If a patient does not tolerate an office biopsy or has cervical stenosis, endovaginal ultrasonography is an effective method to assess thickness of the endometrial echo complex and to evaluate uterine bleeding. The American College of Obstetricians and Gynecologists recommends transvaginal ultrasonography as a reasonable alternative to endometrial sampling for the evaluation of an initial episode of bleeding in a postmenopausal woman ⁴⁴.

Endovaginal ultrasonography has a sensitivity of greater than 96% for ruling out endometrial carcinoma if the endometrial echo complex is less than 5 mm. Persistent bleeding despite a thin stripe still warrants tissue biopsy because of the risk of missing a type 2 cancer that is not associated with hyperplasia and thickening of the endometrial echo complex ⁴⁵. If hyperplasia is diagnosed by office biopsy, one should consider D&C and hysteroscopy to more definitely rule out atypia or cancer prior to conservative medical management. This is because blind dilation and curettage (D&C) and Pipelle endometrial biopsies both sample only 50-60% of the endometrial cavity, and can miss focal lesions ⁴⁶.

Endometrial hyperplasia treatment

The accurate diagnosis of endometrial hyperplasia type is vital for appropriate treatment based on risk of cancer without over or under treatment ⁴⁷. Once a tissue diagnosis of endometrial hyperplasia is made, treatment depends on the type of hyperplasia, the patient’s symptoms such as severity of bleeding, surgical risks, and wish for future childbearing.

In many cases, endometrial hyperplasia can be treated with progestin (man made progesterone). Progesterone induce secretory changes in the endometrium and counterbalance the stimulatory effects of estrogen. Progestins can effectively treat endometrial hyperplasia to control bleeding and prevent progression to cancer. They can serve as prevention of recurrence in those with continued risk factors ⁴⁷. Progestin is given orally, in a shot, in an intrauterine device (IUD), or as a vaginal cream. How much and how long you take it depends on your age and the type of endometrial hyperplasia you have. Treatment with progestin may cause vaginal bleeding like a period.

Multiple regimens of progestin therapy have been found effective in reversing endometrial hyperplasia, including the following ²³.:

• Medroxyprogesterone acetate – MPA (Provera), 10-20 mg once daily or cyclic 12-14 days per month
• Depot Medroxyprogesterone (Depo-provera) 150 mg IM every 3 months
• Micronized vaginal progesterone (Prometrium), 100-200 mg once daily or cyclic 12-14 days per month
• Levonorgestrel-containing IUD (Mirena), 20 mcg/day ⁴⁸
• Megestrol acetate (Megace), 40-200 mg per day, usually reserved for women with atypical hyperplasia

Benign endometrial hyperplasia responds well to progestins. More than 98% of women with endometrial hyperplasia treated with cyclic progestins experienced regression of the disease in 3-6 months ⁴⁹. However, if you have endometrial intraepithelial neoplasia (EIN) or atypical endometrial hyperplasia changes in the lining of your uterus, the risk of endometrial cancer is increased by 42% ¹⁵. Hysterectomy may be a treatment option if you do not want another pregnancy. Talk with your doctor about the right treatment for you.

Interest is increasing in the use of levonorgestrel-releasing intrauterine system (LNG-IUS) as a treatment option for endometrial hyperplasia to deliver local effect with less systemic side-effects ⁵⁰. A 15-year study using the levonorgestrel-releasing intrauterine system (LNG-IUS) for 34 patients with endometrial hyperplasia found regression to atrophic endometrium in 94% ⁵¹. However, this study had only 4 (12%) patients with atypical hyperplasia ⁵¹. A meta-analysis of 24 observational studies, including 1,001 cases, indicate that progestins appeared to induce a lower disease regression rate than levonorgestrel-releasing intrauterine system (LNG-IUS) in the treatment of complex and atypical endometrial hyperplasia. However, a controlled clinical trial is necessary to confirm the observational findings. The authors feel data using the levonorgestrel-releasing intrauterine device (LNG-IUD) as the only treatment modality for atypical hyperplasia or endometrial cancer are still limited ⁵².

The Postmenopausal Estrogen/Progestin Interventions (PEPI) trial showed a 94% normalization of complex or atypical hyperplasia in 45 women treated with progestins ³⁰. One cohort study found that 115 patients with complex atypical hyperplasia had approximately 30% persistence or progression of disease whether treated with progestins or not. However, of 70 patients with atypical hyperplasia, 67% vs 27% had persistence or progression when not treated with progestins ⁵³.

If the patient has not completed childbearing or is not a surgical candidate, then concurrent cancer must first be ruled out by D&C with hysteroscopy prior to medical management. Experts recommend megestrol acetate for endometrial intraepithelial neoplasia (EIN), with or without levonorgestrel IUD (intrauterine device) for patients wishing to preserve fertility or for those too ill for surgical management. Any progestin should be adequate for treatment of benign hyperplasia or for maintenance after resolution of endometrial intraepithelial neoplasia (EIN). Patient should be sampled to assess for response every 3 to 6 months for regression to normal endometrium. If there is inadequate response in 6 months, consider increasing dose or changing progestins. There is no proven protocol for selection or dosing. Continued surveillance after regression of the lesion is recommended every 6 to 12 months if risk factors persist. Repeat biopsy is also indicated for recurrent abnormal bleeding or discharge. Prevention of recurrence include use of daily or cyclic progesterone, indwelling levonorgestrel IUD, along with weight loss for obese patients.

Due to the large number of young anovulatory women diagnosed with atypical endometrial hyperplasia or endometrial intraepithelial neoplasia (EIN) or early endometrial cancer, numerous studies have examined the outcome of fertility-sparing hormonal therapy. A meta-analysis of 24 observational studies that included a total of 151 women with atypical endometrial hyperplasia found that those who had fertility-sparing treatments had 86% regression, 26% relapse, and live birth rate of 26% ⁵⁴.

Another review of complex atypical endometrial hyperplasia or endometrial intraepithelial neoplasia (EIN) patients who underwent progestin therapy found a complete response rate of 66% ⁵⁵. Median time to response was 6 months. Recurrence rate after initial response was 23%. During study follow-up time of 39 months, 41% of patients with atypical hyperplasia became pregnant ⁵⁵.

The Gynecologic Oncology Group pathologic study with biopsy diagnosis of atypical hyperplasia found 42.6% concurrent endometrial carcinoma on hysterectomy specimen; 31% of these had myometrial invasion, including 10.6% with outer half myometrial invasion ¹⁵. Others also found atypical endometrial hyperplasia on office biopsy or D&C was associated with a 48-56% cancer rate on permanent pathology. Thus, if a hysterectomy is planned for treatment of atypical hyperplasia based on office endometrial biopsy, the authors recommend having a gynecologic oncologist be primary surgeon, or be available for surgical staging if needed based on frozen section of uterine specimen ⁵⁶, ⁴⁶. Patients should be counseled and consented for washings, hysterectomy, possible bilateral-salpingo-oophorectomy and lymph node dissection depending on intra-op exam or frozen pathology findings. If a D&C with hysteroscopy had been performed to rule out concurrent carcinoma more definitively, an oncologic surgeon is likely not needed. Due to the risk of cancer, supracervical, morcellation, or endometrial ablation is not recommended. While a simple hysterectomy is adequate for definitive treatment of hyperplasia, one can consider bilateral salpingo-oophorectomy in perimenopausal or postmenopausal women due to possibility of cancer on permanent section. Ovaries should only be removed if cancer is diagnosed in premenopausal women. They should be counseled a second surgery may be required to remove ovaries and perform lymph node staging if cancer if found on final pathology.

The need for hysterectomy to exclude concurrent myoinvasive endometrioid adenocarcinoma presents a barrier to nonsurgical management of endometrial hyperplasia. A Gynecologic Oncology Group study examined the histomorphometric 4-class rule (4C), which measures epithelial abundance, thickness, and nuclear variation as applied to diagnostic biopsies to predict myoinvasive cancer outcomes at hysterectomy ⁵⁷. Women with endometrial biopsies or curettages with a community diagnosis of atypical endometrial hyperplasia were enrolled in a clinical trial in which subsequent hysterectomy was scored for endometrial adenocarcinoma, and 4C rule ability to predict cancer outcomes was measured. Qualifying biopsies were stratified into high-risk and low-risk histomorphometric subgroups ⁵⁷. Assignment to a high-risk category by 4C rule was highly sensitive in predicting any (71%) or deeply (92%) myoinvasive adenocarcinoma at hysterectomy, and assignment to a low-risk group had a high negative predictive value for absence of any (90%) or deeply (99%) myoinvasive disease ⁵⁷. At present, this use of histomorphometry is most suited to a centralized reference laboratory performing histomorphometry for a variety of diagnostic applications. However, in the future, formal histomorphometry of endometrial biopsies using the 4C rule may become a more common method to identify a subset of women with premalignant disease who are unlikely to have concurrent myoinvasive adenocarcinoma and therefore may qualify for nonsurgical therapy.

Endometrial hyperplasia prognosis

Several studies have shown that progestogen (synthetic forms of progesterone) therapy leads to a high rate of regression in endometrial hyperplasia without atypia (89% to 96%) ⁵², ⁴⁸, ⁴⁹. However, in the presence of endometrial intraepithelial neoplasia (EIN), there is a reduction in the success rate of progestogen therapy ¹⁵. The presence of atypical endometrial hyperplasia or endometrial intraepithelial neoplasia (EIN) has a higher risk of progression to invasive malignancy – as high as 27.5% if not treated ⁵⁸. Also, atypical endometrial hyperplasia or endometrial intraepithelial neoplasia (EIN) has a possibility of coexistent endometrial malignancy in 43% of cases ¹⁵.

Endometrial cancer types

Endometrial cancer also called endometrial carcinoma, starts in the cells of the inner lining of the uterus (the endometrium). This is the most common type of cancer in the uterus ⁵⁹.

Endometrial carcinomas can be divided into different types based on how the cells look under the microscope. These are called histologic types. They include:

• Adenocarcinoma (most endometrial cancers are a type of adenocarcinoma called endometrioid cancer or endometrial adenocarcinoma)
• Uterine carcinosarcoma
• Squamous cell carcinoma
• Small cell carcinoma
• Transitional carcinoma
• Serous carcinoma

Clear-cell carcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, dedifferentiated carcinoma, and serous adenocarcinoma are less common types of endometrial adenocarcinomas. They tend to grow and spread faster than most types of endometrial cancer. They often have spread outside the uterus by the time they’re diagnosed.

Endometrioid adenocarcinoma

Endometrioid adenocarcinoma also called endometrial adenocarcinoma or endometrioid cancer, is the most common type of adenocarcinoma, by far. Endometrioid cancers start in gland cells and look a lot like the normal uterine lining (endometrium). Some of these cancers have squamous cells (squamous cells are flat, thin cells), as well as glandular cells.

There are many variants (or sub-types) of endometrioid cancers including:

• Adenocarcinoma, (with squamous differentiation)
• Adenoacanthoma
• Adenosquamous (or mixed cell)
• Secretory carcinoma
• Ciliated carcinoma
• Villoglandular adenocarcinoma

Endometrioid cancers are often diagnosed at an early stage and so are usually treated successfully.

Uterine carcinosarcoma

Uterine carcinosarcoma tumors are also known as malignant mixed mesodermal tumors or malignant mixed mullerian tumors. They make up about 3% of uterine cancers. Uterine carcinosarcoma starts in the endometrium and has features of both endometrial carcinoma and sarcoma. Sarcoma is cancer that starts in muscle cells of the uterus. In the past, uterine carcinosarcoma was considered a different type of uterine cancer called uterine sarcoma, but doctors now believe that uterine carcinosarcoma is an endometrial carcinoma that’s so abnormal it no longer looks much like the cells it came from (it’s poorly differentiated).

Uterine carcinosarcoma is a type 2 endometrial carcinoma.

Uterine sarcoma

Uterine sarcomas start in the muscle layer (myometrium) or supporting connective tissue of the uterus (the serosa or perimterium). Uterine sarcomas are a type of soft tissue sarcoma and are much less common than endometrial cancer. These include uterine leiomyosarcomas and endometrial stromal sarcomas. Leiomyosarcoma is the most common sarcoma of the womb. It is a cancer of the muscle wall. The treatment you need for this type of uterine cancer is not the same as other types of uterine cancer.

Most uterine sarcomas are put into categories, based on the type of cell they start in:

• Uterine leiomyosarcoma: These tumors start in the muscular wall of the uterus (the myometrium). They are by far the most common type. These tumors can grow and spread quickly.
• Endometrial stromal sarcoma: Endometrial stromal sarcoma tumors start in the supporting connective tissue (stroma) of the lining of the uterus (the endometrium). These cancers are rare.
  • If the tumor is low grade, the cancer cells do not look very different from normal cells and the tumor tends to grow slowly. Women with low-grade endometrial stromal sarcoma have a better outlook (prognosis) than women with other kinds of uterine sarcomas.
  • High-grade endometrial stromal sarcoma means the cancer cells look very different from normal cells, and the tumor is growing quickly. This type of endometrial stromal sarcoma is most often found when the tumor is already large and/or has spread. These tumors are hard to treat.
• Undifferentiated sarcoma: These cancers may start in the endometrium or the myometrium. They grow and spread quickly and tend to have a poor outlook.

Type 1 and type 2 endometrial cancer

Doctors sometimes divide endometrial cancers into 2 types ⁶⁰.

• Type 1 endometrial cancers are the most common type representing more than 70% of cases. They are usually endometrioid adenocarcinomas and are associated with unopposed estrogen stimulation or due to excess estrogen in the body. They are generally low grade, slow growing and less likely to spread ⁶¹.
• Type 2 endometrial cancers are not linked to excess estrogen. Type 2 endometrial cancer accounts for only 10% of endometrial cancers, but it is associated with 40% of related deaths ⁶¹. Type 2 tumors are more likely to be high grade and of papillary serous or clear cell histologic type. They are generally faster growing, carry a poor prognosis and have a high risk of relapse and more likely to spread. They include uterine serous carcinomas and clear cell carcinomas.

Endometrial cancer grades

The grade of an endometrial cancer is based on how much the cancer cells are organized into glands that look like the glands found in a normal, healthy endometrium. The grade of an endometrial cancer gives your doctor an idea of how quickly or slowly the cancer might grow and whether it is likely to spread. In lower-grade cancers (grades 1 and 2), more of the cancer cells form glands. In higher-grade cancers (grade 3), more of the cancer cells are disorganized and do not form glands.

Grading is a way of dividing cancer cells into groups depending on how much the cells look like normal cells.

• Grade 1 endometrial cancers also called low grade or well differentiated, have 95% or more of the cancer tissue forming glands. They tend to be slow growing and are less likely to spread than higher grade cancer cells.
• Grade 2 endometrial cancers also called moderately differentiated or moderate grade, have between 50% and 94% of the cancer tissue forming glands.
• Grade 3 endometrial cancers also called poorly differentiated or high grade, have less than half of the cancer tissue forming glands. Grade 3 cancers tend to be aggressive (they grow and spread fast) and have a worse outlook than lower-grade cancers.

Grades 1 and 2 endometrioid cancers are type 1 endometrial cancers. Type 1 cancers are usually not very aggressive and they don’t spread to other tissues quickly. Type 1 endometrial cancers are thought to be caused by too much estrogen. They sometimes develop from atypical hyperplasia, an abnormal overgrowth of cells in the endometrium.

A small number of endometrial cancers are type 2 endometrial cancer. Type 2 cancers are more likely to grow and spread outside the uterus, they have a poorer outlook (than type 1 cancers). Doctors tend to treat these cancers more aggressively. They don’t seem to be caused by too much estrogen. Type 2 cancers include all endometrial carcinomas that aren’t type 1, such as papillary serous carcinoma, clear-cell carcinoma, undifferentiated carcinoma, and grade 3 endometrioid carcinoma. These cancers don’t look at all like normal endometrium and so are called poorly differentiated or high-grade.

Endometrial cancer causes

Scientists do not yet know exactly what causes most cases of endometrial cancer, but they do know there are risk factors, like obesity and hormone imbalance, that are strongly linked to endometrial cancer. A great deal of research is going on to learn more about endometrial cancer.

Scientists know that most endometrial cancer cells contain estrogen and/or progesterone receptors on their surfaces. Somehow, interaction of these receptors with their hormones leads to increased growth of the endometrium. This can mark the beginning of cancer. The increased growth can become more and more abnormal until it develops into a cancer.

As noted in the risk factors section below, many of the known endometrial cancer risk factors affect the balance between estrogen and progesterone in the body.

Scientists are learning more about changes (mutations) in the DNA of certain genes that occur when normal endometrial cells become cancerous. The mutation turns normal, healthy cells into abnormal cells. Healthy cells grow and multiply at a set rate, eventually dying at a set time. Abnormal cells grow and multiply out of control, and they don’t die at a set time. The accumulating abnormal cells form a mass (tumor). Cancer cells invade nearby tissues and can separate from an initial tumor to spread elsewhere in the body (metastasize).

Endometrial cancer risk factors

A risk factor is anything that affects your chance of getting a disease such as cancer. Different cancers have different risk factors. Some risk factors, like smoking, can be changed. Others, like a person’s age or family history, can’t be changed.

Although certain factors increase a woman’s risk for developing endometrial cancer, they do not always cause the disease. Many women with one or more risk factors never develop endometrial cancer.

Some women with endometrial cancer do not have any known risk factors. Even if a woman with endometrial cancer has one or more risk factors, there is no way to know which, if any, of these factors was responsible for her cancer.

Many factors affect the risk of developing endometrial cancer, including:

• Things that affect hormone levels, like taking estrogen after menopause, birth control pills, or tamoxifen; the number of menstrual cycles (over a lifetime), pregnancy, obesity, certain ovarian tumors, and polycystic ovarian syndrome (PCOS)
• Use of an intrauterine device (IUD)
• Never having been pregnant
• Age
• Obesity
• Diet and exercise
• Type 2 diabetes
• Family history (having close relatives with endometrial or colorectal cancer)
• Having been diagnosed with breast or ovarian cancer in the past
• Having been diagnosed with endometrial hyperplasia in the past
• Treatment with radiation therapy to the pelvis to treat another cancer

Some of these, like pregnancy, birth control pills, and the use of an intrauterine device are linked to a lower risk of endometrial cancer, while many are linked to a higher risk. These factors and how they affect endometrial cancer risk are discussed in more detail below.

Changes in the balance of female hormones in the body

A woman’s hormone balance plays a part in the development of most endometrial cancers. Many of the risk factors for endometrial cancer affect estrogen levels. Before menopause, the ovaries are the major source of the 2 main types of female hormones — estrogen and progesterone. The balance between these hormones changes each month during a woman’s menstrual cycle. This produces a woman’s monthly periods and keeps the endometrium healthy. A shift in the balance of these hormones toward more estrogen increases a woman’s risk for endometrial cancer. A disease or condition that increases the amount of estrogen, but not the level of progesterone, in your body can increase your risk of endometrial cancer. Examples include irregular ovulation patterns, which might happen in polycystic ovary syndrome, obesity and diabetes. A rare type of ovarian tumor that secretes estrogen also can increase the risk of endometrial cancer.

After menopause, the ovaries stop making these hormones, but a small amount of estrogen is still made naturally in fat tissue. Estrogen from fat tissue has a bigger impact after menopause than it does before menopause. Also taking hormones after menopause that contain estrogen but not progesterone increases the risk of endometrial cancer.

Estrogen therapy

Treating the symptoms of menopause with hormones is known as menopausal hormone therapy (or sometimes hormone replacement therapy [HRT]). Estrogen is the major part of this treatment. Estrogen treatment can help reduce hot flashes, improve vaginal dryness, and help prevent the weakening of the bones (osteoporosis) that can occur with menopause.

But using estrogen alone (without progesterone) can lead to endometrial cancer in women who still have a uterus. To lower that risk, a progestin (progesterone or a drug like it) must be given along with estrogen. This is called combination hormone therapy.

Women who take progesterone along with estrogen to treat menopausal symptoms do not have an increased risk of endometrial cancer. Still, taking this combination increases a woman’s chance of developing breast cancer and also increases the risk of serious blood clots.

If you are taking (or plan to take) hormones after menopause, it’s important to discuss the possible risks (including cancer, blood clots, heart attacks, and stroke) with your doctor.

Like any other medicine, hormones should be used at the lowest dose needed and for the shortest possible time to control symptoms. As with any other medicine you take for a long time, you’ll need to see your doctor regularly. Experts recommend yearly follow-up pelvic exams. If you have any abnormal bleeding or discharge from your vagina you should see a health care provider right away. Do not wait until your next check-up.

Birth control pills

Using birth control pills (oral contraceptives) lowers the risk of endometrial cancer. The risk is lowest in women who take the pill for a long time, and this protection lasts for at least 10 years after a woman stops taking the pill. But it’s important to look at all of the risks and benefits when choosing a contraceptive method; endometrial cancer risk is only one factor to consider. It’s a good idea to discuss the pros and cons of different types of birth control with your doctor.

Total number of menstrual cycles

Having more menstrual cycles during a woman’s lifetime raises her risk of endometrial cancer. Starting first menstrual periods (menarche) before age 12 and/or going through menopause later in life raises the risk. Starting periods early is less a risk factor for women with early menopause. Likewise, late menopause may not lead to a higher risk in women whose periods began later in their teens.

Never having been pregnant

The hormonal balance shifts toward more progesterone during pregnancy. So having many pregnancies helps protect against endometrial cancer. Women who have never been pregnant have a higher risk, especially if they were also infertile (unable to become pregnant).

Obesity

Obesity is a strong risk factor for endometrial cancer and linked to hormone changes. A woman’s ovaries produce most of her estrogen before menopause. But fat tissue can change some other hormones (called androgens) into estrogens. This can impact estrogen levels, especially after menopause. Having more fat tissue can increase a woman’s estrogen levels, which increases her endometrial cancer risk.

In comparison with women who stay at a healthy weight, endometrial cancer is twice as common in overweight women (BMI 25 to 29.9), and more than 3 times as common in obese women (BMI > 30).

Gaining weight as you get older age and weight cycling (gaining and losing a lot of weight many times in your life) have also been linked to a higher risk of endometrial cancer after menopause.

Tamoxifen

Tamoxifen is a drug that is used to help prevent and treat breast cancer. Tamoxifen acts as an anti-estrogen in breast tissue, but it acts like an estrogen in the uterus. In women who have gone through menopause, it can cause the uterine lining to grow, which increases the risk of endometrial cancer.

The risk of developing endometrial cancer from tamoxifen is low (less than 1% per year). Women taking tamoxifen must balance this risk against the benefits of this drug in treating and preventing breast cancer. This is an issue women should discuss with their providers. If you are taking tamoxifen, you should have yearly gynecologic exams and should be sure to report any abnormal bleeding, as this could be a sign of endometrial cancer.

Ovarian tumors

A certain type of ovarian tumor, the granulosa cell tumor, often makes estrogen. Estrogen made by one of these tumors isn’t controlled the way hormone release from the ovaries is, and it can sometimes lead to high estrogen levels. The resulting hormone imbalance can stimulate the endometrium and even lead to endometrial cancer. In fact, sometimes vaginal bleeding from endometrial cancer is the first symptom of one of these tumors.

Polycystic ovarian syndrome (PCOS)

Women with a condition called polycystic ovarian syndrome (PCOS) have abnormal hormone levels, such as higher androgen (male hormones) and estrogen levels and lower levels of progesterone. The increase in estrogen relative to progesterone can increase a woman’s chance of getting endometrial cancer. PCOS is also a leading cause of infertility in women.

Using an intrauterine device (IUD)

Women who used an intrauterine device (IUD) for birth control seem to have a lower risk of getting endometrial cancer. Information about this protective effect is limited to IUDs that do not contain hormones. Researchers have not yet studied whether newer types of IUDs that release progesterone have any effect on endometrial cancer risk. But these IUDs are sometimes used to treat pre-cancers and early endometrial cancers in women who wish to be able to get pregnant in the future.

Age

As you get older, your risk of endometrial cancer increases. Endometrial cancer occurs most often after menopause.

Diet and exercise

A high-fat diet can increase the risk of many cancers, including endometrial cancer. Because fatty foods are also high-calorie foods, a high-fat diet can lead to obesity, which is a well-known endometrial cancer risk factor. Many scientists think this is the main way in which a high-fat diet raises endometrial cancer risk. Some scientists think that fatty foods may also have a direct effect on how the body uses estrogen, which increases endometrial cancer risk.

Physical activity lowers the risk of endometrial cancer. Many studies have found that women who exercise more have a lower risk of endometrial cancer, while others suggest that women who spent more time sitting have a higher risk.

Diabetes

Endometrial cancer may be about twice as common in women with type 2 diabetes. But diabetes is more common in people who are overweight and less active, which are also risk factors for endometrial cancer. This makes it hard to find a clear link.

Family history

Endometrial cancer tends to run in some families. Some of these families also have a higher risk for colon cancer. This disorder is called hereditary nonpolyposis colon cancer (HNPCC) or Lynch syndrome. In most cases, hereditary nonpolyposis colon cancer (HNPCC) is caused by a defect in either the mismatch repair gene MLH1 or the gene MSH2. But at least 5 other genes can cause HNPCC: MLH3, MSH6, TGBR2, PMS1, and PMS2. An abnormal copy of any one of these genes reduces the body’s ability to repair damage to its DNA or control cell growth. This results in a very high risk of colon cancer, as well as a high risk of endometrial cancer. Women with this syndrome have a up to a 70% risk of developing endometrial cancer at some point. The risk for women in general is about 3%. The risk of ovarian cancer is also increased.

Some families have a higher rate of only endometrial cancer. These families may have a different genetic disorder that hasn’t been found yet.

Breast or ovarian cancer

Women who have had breast cancer or ovarian cancer may have an increased risk of endometrial cancer, too. Some of the dietary, hormone, and reproductive risk factors for breast and ovarian cancer also increase endometrial cancer risk.

Endometrial hyperplasia

Endometrial hyperplasia is an increased growth of the endometrium. Mild or simple hyperplasia, the most common type, has a very small risk of becoming cancer. It may go away on its own or after treatment with hormone therapy. If the hyperplasia is called “atypical,” it has a higher chance of becoming a cancer. Simple atypical hyperplasia turns into cancer in about 8% of cases if it’s not treated. Complex atypical hyperplasia has a risk of becoming cancer in up to 29% of cases if it’s not treated, and the risk of having an undetected endometrial cancer is even higher. For this reason, complex atypical hyperplasia is usually treated.

Prior pelvic radiation therapy

Radiation used to treat some other cancers can damage the DNA of cells, sometimes increasing the risk of a second type of cancer such as endometrial cancer.

Endometrial cancer prevention

Most cases of endometrial cancer cannot be prevented, but there are some things that may lower your risk of developing this disease.

To reduce your risk of endometrial cancer, you may wish to:

• Get to and stay at a healthy weight. One way to lower endometrial cancer risk is to do what you can to change your risk factors whenever possible. For example, women who are overweight or obese have up to 3½ times the risk of getting endometrial cancer compared with women at a healthy weight. Getting to and maintaining a healthy weight is one way to lower the risk of this cancer.
• Be physically active. Studies have also linked higher levels of physical activity to lower risks of endometrial cancer, so engaging in regular physical activity (exercise) may also be a way to help lower endometrial cancer risk. An active lifestyle can help you stay at a healthy weight, as well as lower the risk of high blood pressure and diabetes (other risk factors for endometrial cancer.
• Discuss pros and cons of hormone therapy with your doctor. Estrogen to treat the symptoms of menopause is available in many different forms like pills, skin patches, shots, creams, and vaginal rings. If you are thinking about using estrogen for menopausal symptoms, ask your doctor about how it will affect your risk of endometrial cancer. Progestins (progesterone-like drugs) can reduce the risk of endometrial cancer in women taking estrogen therapy, but this combination increases the risk of breast cancer. If you still have your uterus and are taking estrogen therapy, discuss this issue with your doctor.
• Consider taking birth control pills. Using oral contraceptives for at least one year may reduce endometrial cancer risk. The risk reduction is thought to last for several years after you stop taking oral contraceptives. Oral contraceptives have side effects, though, so discuss the benefits and risks with your doctor.
• Get treated for endometrial problems. Getting proper treatment of pre-cancerous disorders of the endometrium is another way to lower the risk of endometrial cancer. Most endometrial cancers develop over a period of years. Many are known to follow and possibly start from less serious abnormalities of the endometrium called endometrial hyperplasia. Some cases of hyperplasia will go away without treatment, but it sometimes needs to be treated with hormones or even surgery. Treatment with progestins and a dilation and curettage (D&C) or hysterectomy can prevent hyperplasia from becoming cancerous. Abnormal vaginal bleeding is the most common symptom of endometrial pre-cancers and cancers, and it needs to be reported and evaluated right away.
• Hereditary nonpolyposis colon cancer (HNPCC). Women with hereditary nonpolyposis colon cancer (HNPCC or Lynch syndrome) have a very high risk of endometrial cancer. Most experts recommend that a woman with HNPCC have her uterus, ovaries, and fallopian tubes removed (a hysterectomy and bilateral salpingo-oophorectomy) after she’s finished having children to prevent endometrial cancer.

Endometrial cancer signs and symptoms

There are a few symptoms that may point to endometrial cancer, but some are more common as this cancer becomes advanced.

Unusual vaginal bleeding, spotting, or other discharge

About 90% of women diagnosed with endometrial cancer have abnormal vaginal bleeding, such as a change in their periods or bleeding between periods or after menopause. This symptom can also occur with some non-cancerous conditions, but it is important to have a doctor look into any irregular bleeding right away. If you have gone through menopause already, it’s especially important to report any vaginal bleeding, spotting, or abnormal discharge to your doctor.

Non-bloody vaginal discharge may also be a sign of endometrial cancer. Even if you cannot see blood in the discharge, it does not mean there is no cancer. In about 10% of cases, the discharge associated with endometrial cancer is not bloody. Any abnormal discharge should be checked out by your doctor.

Pelvic pain, a mass, and weight loss

Pain in the pelvis, feeling a mass (tumor), and losing weight without trying can also be symptoms of endometrial cancer. These symptoms are more common in later stages of the disease. Still, any delay in seeking medical help may allow the disease to progress even further. This lowers the odds of treatment being successful.

Although any of these symptoms can be caused by things other than cancer, it’s important to have them checked out by a doctor.

Can endometrial cancer be found early?

In most cases, noticing any signs and symptoms of endometrial cancer, such as abnormal vaginal bleeding or discharge (that is increasing in amount, occurring between periods, or occurring after menopause), and reporting them right away to your doctor allows the disease to be diagnosed at an early stage. Early detection improves the chances that your cancer will be treated successfully. But some endometrial cancers may reach an advanced stage before signs and symptoms can be noticed.

Early detection tests (Screening)

Early detection (also called screening) refers to the use of tests to find a disease such as cancer in people who do not have symptoms of that disease.

Women at average endometrial cancer risk

At this time, there are no screening tests or exams to find endometrial cancer early in women who are at average endometrial cancer risk and have no symptoms.

The American Cancer Society recommends that, at menopause, all women should be told about the risks and symptoms of endometrial cancer and strongly encouraged to report any vaginal bleeding, discharge, or spotting to their doctor.

Women should talk to their doctors about getting regular pelvic exams. A pelvic exam can find some cancers, including some advanced uterine cancers, but it is not very effective in finding early endometrial cancers.

The Pap test, which screens women for cervical cancer, can occasionally find some early endometrial cancers, but it’s not a good test for this type of cancer.

Women at increased endometrial cancer risk

The American Cancer Society recommends that most women at increased risk should be informed of their risk and be advised to see their doctor whenever they have any abnormal vaginal bleeding. This includes women whose risk of endometrial cancer is increased due to increasing age, late menopause, never giving birth, infertility, obesity, diabetes, high blood pressure, estrogen treatment, or tamoxifen therapy.

Women who have (or may have) hereditary non-polyposis colon cancer (HNPCC, sometimes called Lynch syndrome) have a very high risk of endometrial cancer. If several family members have had colon or endometrial cancer, you might want to think about having genetic counseling to learn about your family’s risk of having HNPCC.

If you (or a close relative) have genetic testing and are found to have a mutation in one of the genes for HNPCC, you are at high risk of getting endometrial cancer.

The American Cancer Society recommends that women who have (or may have) HNPCC be offered yearly testing for endometrial cancer with endometrial biopsy beginning at age 35. Their doctors should discuss this test with them, including its risks, benefits, and limitations. This applies to women known to carry HNPCC-linked gene mutations, women who are likely to carry such a mutation (those with a mutation known to be present in the family), and women from families with a tendency to get colon cancer where genetic testing has not been done.

Another option for a woman who has (or may have) HNPCC would be to have a hysterectomy once she is done having children.

Endometrial cancer diagnosis

If you have any of the symptoms of endometrial cancer, you should see a doctor right away. Your doctor will ask you about your symptoms including what they are, when you get them and whether anything you do makes them better or worse. Your doctor will also do a physical exam and a pelvic exam.

Your doctor decide about whether to refer you for tests or to a specialist. If you are diagnosed with endometrial cancer you will have more tests to find out how big it is and whether it has spread. This is called staging.

Tests and procedures used to diagnose endometrial cancer include:

Pelvic examination

During a pelvic exam, your doctor carefully inspects the outer portion of your genitals (vulva), and then inserts two fingers of one hand into your vagina and simultaneously presses the other hand on your abdomen to feel your uterus and ovaries. He or she also inserts a device called a speculum into your vagina. The speculum opens your vagina so that your doctor can view your vagina and cervix for abnormalities.

Ultrasound

Ultrasound is often one of the first tests used to look at the uterus, ovaries, and fallopian tubes in women with a possible gynecologic problem. Ultrasound tests use sound waves to take pictures of parts of the body. A small instrument called a transducer or probe gives off sound waves and picks up the echoes as they bounce off the organs. A computer translates the echoes into pictures.

For a pelvic ultrasound, the transducer is placed on the skin of the lower part of the abdomen. Often, to get good pictures of the uterus, ovaries, and fallopian tubes, the bladder needs be full. That is why women getting a pelvic ultrasound are asked to drink lots of water before the exam.

A transvaginal ultrasound (TVUS) is often preferred for looking at the uterus. For this test, the TVUS probe (that works the same way as the ultrasound transducer) is put into the vagina. Images from the TVUS can be used to see if the uterus contains a mass (tumor), or if the endometrium is thicker than usual, which can be a sign of endometrial cancer. It may also help see if a cancer is growing into the muscle layer of the uterus (myometrium).

A small tube may be used to put salt water (saline) into the uterus before the ultrasound. This helps the doctor see the uterine lining more clearly. This procedure is called a saline infusion sonogram or hysterosonogram. Sonogram is another term for ultrasound.

Ultrasound can be used to see endometrial polyps (growths) , measure how thick the endometrium is, and can help doctors pinpoint the area they want to biopsy.

Endometrial tissue sampling

To find out exactly what kind of endometrial change is present, the doctor must take out some tissue so that it can be tested and looked at with a microscope. Endometrial tissue can be removed by endometrial biopsy or by dilation and curettage (D&C) with or without a hysteroscopy. A gynecologist usually does these procedures.

Endometrial biopsy

An endometrial biopsy is the most commonly performed test for endometrial cancer and is very accurate in postmenopausal women. It can be done in the doctor’s office. In this procedure a very thin flexible tube is inserted into the uterus through the cervix. Then, using suction, a small amount of endometrium is removed through the tube. The suctioning takes about a minute or less. The discomfort is similar to menstrual cramps and can be helped by taking a nonsteroidal anti-inflammatory drug such as ibuprofen before the procedure. Sometimes numbing medicine (local anesthetic) is injected into the cervix just before the procedure to help reduce the pain.

Hysteroscopy

For this technique doctors insert a tiny telescope (about 1/6 inch in diameter) into the uterus through the cervix. To get a better view of the inside of the uterus, the uterus is filled with salt water (saline). This lets the doctor see and biopsy anything abnormal, such as a cancer or a polyp. This is usually done using a local anesthesia (numbing medicine) with the patient awake.

Dilation and curettage (D&C)

If the endometrial biopsy sample doesn’t provide enough tissue, or if the biopsy suggests cancer but the results are uncertain, a D&C must be done. In this outpatient procedure, the opening of the cervix is enlarged (dilated) and a special instrument is used to scrape tissue from inside the uterus. This may be done with or without a hysteroscopy.

This procedure takes about an hour and may require general anesthesia (where you are asleep) or conscious sedation (given medicine into a vein to make you drowsy) either with local anesthesia injected into the cervix or a spinal (or epidural). A D&C is usually done in an outpatient surgery area of a clinic or hospital. Most women have little discomfort after this procedure.

Testing endometrial tissue samples

Endometrial tissue samples removed by biopsy or D&C are looked at with a microscope to see whether cancer is present. If cancer is found, the lab report will state what type of endometrial cancer it is (like endometrioid or clear cell) and what grade it is.

Endometrial cancer is graded on a scale of 1 to 3 based on how much it looks like normal endometrium. Women with lower grade cancers are less likely to have advanced disease or recurrences.

Testing for gene and protein changes in the cancer cells

If the doctor suspects hereditary non-polyposis colon cancer (HNPCC) as an underlying cause of the endometrial cancer, the tumor cells can be tested for protein and gene changes. Examples of HNPCC-related changes include:

• Having fewer mismatch repair (MMR) proteins
• Defects in mismatch repair genes (dMMR)
• DNA changes (high levels of microsatellite instability, or MSI-H) that can happen when one of the genes that causes HNPCC is faulty

If these protein or DNA changes are present, the doctor may suggest genetic testing for the genes that cause HNPCC.

Testing the cancer cells for dMMR, MSI-H, and/or a high tumor mutational burden (TMB-H) might also be done to see if treatment with immunotherapy might be an option, especially for more advanced endometrial cancers.

Tests to look for cancer spread

If the doctor suspects that your cancer is advanced, you will probably have to have other tests to look for cancer spread.

Chest x-ray

A plain x-ray of your chest may be done to see if cancer has spread to your lungs.

Computed tomography (CT)

The CT scan is an x-ray procedure that creates detailed, cross-sectional images of your body. For a CT scan, you lie on a table while an X-ray takes pictures. Instead of taking one picture, like a standard x-ray, a CT scanner takes many pictures as the camera rotates around you. A computer then combines these pictures into an image of a slice of your body. The machine will take pictures of many slices of the part of your body that is being studied.

CT scans are not used to diagnose endometrial cancer. However, they may be helpful to see whether the cancer has spread to other organs and to see if the cancer has come back after treatment.

Magnetic resonance imaging (MRI)

MRI scans use radio waves and strong magnets instead of x-rays. The energy from the radio waves is absorbed and then released in a pattern formed by the type of tissue and by certain diseases. A computer translates the pattern of radio waves given off by the tissues into a very detailed image of parts of the body. This creates cross sectional slices of the body like a CT scanner and it also produces slices that are parallel with the length of your body.

MRI scans are particularly helpful in looking at the brain and spinal cord. Some doctors also think MRI is a good way to tell whether, and how far, the endometrial cancer has grown into the body of the uterus. MRI scans may also help find enlarged lymph nodes with a special technique that uses very tiny particles of iron oxide. These are given into a vein and settle into lymph nodes where they can be spotted by MRI.

Positron emission tomography (PET)

In this test radioactive glucose (sugar) is given to look for cancer cells. Because cancers use glucose (sugar) at a higher rate than normal tissues, the radioactivity will tend to concentrate in the cancer. A scanner can spot the radioactive deposits. This test can be helpful for spotting small collections of cancer cells. Special scanners combine a PET scan with a CT to more precisely locate areas of cancer spread. PET scans are not a routine part of the work-up of early endometrial cancer, but may be used for more advanced cases.

Cystoscopy and proctoscopy

If a woman has problems that suggest the cancer has spread to the bladder or rectum, the inside of these organs will probably be looked at through a lighted tube. In cystoscopy the tube is placed into the bladder through the urethra. In proctoscopy the tube is placed in the rectum. These exams allow the doctor to look for possible cancers. Small tissue samples can also be removed during these procedures for pathologic (microscopic) testing. They can be done using a local anesthetic but some patients may require general anesthesia. Your doctor will let you know what to expect before and after the procedure. These procedures were used more often in the past, but now are rarely part of the work up for endometrial cancer.

Blood tests

Complete blood count

The complete blood count (CBC) is a test that measures the different cells in the blood, such as the red blood cells, the white blood cells, and the platelets. Endometrial cancer can cause bleeding, which can lead to low red blood cell counts ( anemia).

CA-125 blood test

CA-125 is a substance released into the bloodstream by many, but not all, endometrial and ovarian cancers. If a woman has endometrial cancer, a very high blood CA-125 level suggests that the cancer has probably spread beyond the uterus. Some doctors check CA-125 levels before surgery or other treatment. If they are elevated, they can be checked again to find out how well the treatment is working (for example, levels will drop after surgery if all the cancer is removed).

CA-125 levels are not needed to diagnose endometrial cancer, and so this test isn’t ordered on all patients.

Endometrial cancer staging

After a woman is diagnosed with endometrial cancer, doctors will try to figure out if it has spread, and if so, how far. This process is called staging. The stage of a cancer describes the amount of cancer in the body. It helps determine how serious the cancer is and how best to treat it. The stage is one of the most important factors in deciding how to treat the cancer and determining how successful the treatment might be.

Endometrial cancer stages range from stage I (1) through IV (4). As a rule, the lower the number, the less the cancer has spread. A higher number, such as stage IV (4), means cancer has spread more. And within a stage, an earlier letter means a lower stage. Although each person’s cancer experience is unique, cancers with similar stages tend to have a similar outlook and are often treated in much the same way.

How is the stage determined?

The 2 systems used for staging endometrial cancer, the FIGO (International Federation of Gynecology and Obstetrics) system and the American Joint Committee on Cancer (AJCC) TNM staging system are basically the same.

They both stage (classify) this cancer based on 3 factors:

• The extent (size) of the tumor (T): How far has the cancer grown into the uterus? Has the cancer reached nearby structures or organs?
• The spread to nearby lymph nodes (N): Has the cancer spread to the lymph nodes in the pelvis or around the aorta (the main artery that runs from the heart down along the back of the abdomen and pelvis). Also called para-aortic lymph nodes.
• The spread (metastasis) to distant sites (M): Has the cancer spread to distant lymph nodes or distant organs?

Numbers or letters after T, N, and M provide more details about each of these factors. Higher numbers mean the cancer is more advanced. Once a person’s T, N, and M categories have been determined, this information is combined in a process called stage grouping to assign an overall stage.

The staging system in the table below uses the pathologic stage (also called the surgical stage). It is determined by examining tissue removed during an operation. This is also known as surgical staging. Sometimes, if surgery is not possible right away, the cancer will be given a clinical stage instead. This is based on the results of a physical exam, biopsy, and imaging tests done before surgery. For more information see Cancer Staging.

The system described below is the most recent AJCC system. It went into effect January 2018.

Endometrial cancer staging can be complex, so ask your doctor to explain it to you in a way you understand.

Table 2. Endometrial cancer staging

TNM Stage	Stage grouping	FIGO Stage	Stage description*
1	T1 N0 M0	1	The cancer is growing inside the uterus. It may also be growing into the glands of the cervix, but not into the supporting connective tissue of the cervix (T1). It has not spread to nearby lymph nodes (N0) or to distant sites (M0).
1A	T1a N0 M0	1A	The cancer is in the endometrium (inner lining of the uterus) and may have grown less than halfway through the underlying muscle layer of the uterus (the myometrium) (T1a). It has not spread to nearby lymph nodes (N0) or to distant sites (M0).
1B	T1b N0 M0	1B	The cancer has grown from the endometrium into the myometrium. It has grown more than halfway through the myometrium, but has not spread beyond the body of the uterus (T1b). It has not spread to nearby lymph nodes (N0) or to distant sites (M0).
2	T2 N0 M0	2	The cancer has spread from the body of the uterus and is growing into the supporting connective tissue of the cervix (called the cervical stroma). But it has not spread outside the uterus (T2). It has not spread to nearby lymph nodes (N0) or to distant sites (M0).
3	T3 N0 M0	3	The cancer has spread outside the uterus, but has not spread to the inner lining of the rectum or urinary bladder (T3). It has not spread to nearby lymph nodes (N0) or to distant sites (M0).
3A	T3a N0 M0	3A	The cancer has spread to the outer surface of the uterus (called the serosa) and/or to the fallopian tubes or ovaries (the adnexa) (T3a). It has not spread to nearby lymph nodes (N0) or to distant sites (M0).
3B	T3b N0 M0	3B	The cancer has spread to the vagina or to the tissues around the uterus (the parametrium) (T3b). It has not spread to nearby lymph nodes (N0) or to distant sites (M0).
3C1	T1-T3 N1, N1mi or N1a M0	3C1	The cancer is growing in the body of the uterus. It may have spread to some nearby tissues, but is not growing into the inside of the bladder or rectum (T1 to T3). It has also spread to pelvic lymph nodes (N1, N1mi, or N1a), but not to lymph nodes around the aorta or distant sites (M0).
3C2	T1-T3 N2, N2mi or N2a M0	3C2	The cancer is growing in the body of the uterus. It may have spread to some nearby tissues, but is not growing into the inside of the bladder or rectum (T1 to T3). It has also spread to lymph nodes around the aorta (para-aortic lymph nodes) (N2, N2mi, or N2a), but not to distant sites (M0).
4A	T4 Any N M0		The cancer has spread to the inner lining of the rectum or urinary bladder (called the mucosa) (T4). It may or may not have spread to nearby lymph nodes (Any N), but has not spread to distant sites (M0).
4B	Any T Any N M1	4B	The cancer has spread to inguinal (groin) lymph nodes, the upper abdomen, the omentum, or to organs away from the uterus, such as the lungs, liver, or bones (M1). The cancer can be any size (Any T) and it might or might not have spread to other lymph nodes (Any N).

Footnotes: *The following additional categories are not listed on the table above:

• TX: Main tumor cannot be assessed due to lack of information.
• T0: No evidence of a primary tumor.
• NX: Regional lymph nodes cannot be assessed due to lack of information.

[Source ⁶² ]

Stage 1 endometrial cancer

Stage 1 endometrial cancers are early cancers and the easiest to treat. The cancer is within the uterus. Stage 1 is divided into stage 1A and 1B.

• Stage 1A endometrial cancer means that the cancer may have grown into the muscle wall (myometrium) of the womb, but no more than halfway
• Stage 1B endometrial cancer means the cancer has grown halfway or more into the muscle wall of the uterus

[Source ⁶³]

Stage 2 endometrial cancer

Stage 2 endometrial cancer means the cancer has grown into the cervix.

[Source ⁶⁴ ]

Stage 3 endometrial cancer

Stage 3 endometrial cancer means the cancer has spread outside the womb, but is still within the pelvis. Your doctor may call this locally advanced womb cancer. There are 3 categories of stage 3 endometrial cancer:

• Stage 3A endometrial cancer means the cancer has grown into the outer covering of the uterus (the serosa) and/or to the ovaries, fallopian tubes or ligaments of the uterus.
• Stage 3B endometrial cancer means the cancer has grown into the vagina or to the connective tissue and fat around the uterus and cervix (the parametrium)
• Stage 3C endometrial cancer means the cancer has spread to nearby lymph nodes (glands)

Stage 4 metastatic endometrial cancer

Stage 4 endometrial cancer means the cancer has spread to another area of the body. There are 2 categories of stage 4 endometrial cancer:

• Stage 4A endometrial cancer means the cancer has grown into the bowel or bladder
• Stage 4B endometrial cancer means the cancer has spread to lymph nodes further away or to other parts of the body, such as the lungs, liver, bones or brain (secondary cancers or metastases)

Endometrial cancer survival rates

Survival rates tell you what percentage of people with the same type and stage of cancer are still alive a certain length of time (usually 5 years) after they were diagnosed. These numbers can’t tell you how long you will live, but they may help give you a better understanding about how likely it is that your treatment will be successful.

Statistics on the outlook for a certain type and stage of cancer are often given as 5-year survival rates, but many people live longer – often much longer – than 5 years. The 5-year survival rate is the percentage of people who live at least 5 years after being diagnosed with cancer.

Survival rates are estimates – your outlook can vary based on a number of factors specific to you.

Survival rates don’t tell the whole story

Survival rates are often based on previous outcomes of large numbers of people who had the disease, but they can’t predict what will happen in any particular person’s case. Your doctor can tell you how the numbers below may apply to you, as he or she is familiar with the aspects of your particular situation.

The survival rates below are based on the stage of the cancer at the time it was diagnosed. These rates do not apply to cancers that have come back after treatment or have spread after treatment starts.

The numbers below come from the National Cancer Data Base as published in the AJCC Staging Manual in 2017, and are based on people diagnosed between 2000 and 2002.

Endometrial cancer survival rates

• The 5-year survival rate for women with stage 0 endometrial cancer is 90%*
• The 5-year survival rate for women with stage 1A endometrial cancer is 88%
• The 5-year survival rate for women with stage 1B endometrial cancer is 75%
• The 5-year survival rate for women with stage 2 endometrial cancer is 69%
• The 5-year survival rate for women with stage 3A endometrial cancer is 58%
• The 5-year survival rate for women with stage 3B endometrial cancer is 50%
• The 5-year survival rate for women with stage 3C endometrial cancer is 47%
• The 5-year survival rate for women with stage 4A endometrial cancer is 17%
• The 5-year survival rate for women with stage 4B endometrial cancer is 15%

*The new staging system that went into effect January 2018 no longer includes Stage 0 cancers.

Endometrial cancer Survival by stage

The National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database tracks 5-year relative survival rates for endometrial cancer in the United States, based on how far the cancer has spread ³. The SEER database, however, does not group cancers by American Joint Committee on Cancer (AJCC) TNM Staging System stages (stage 1, stage 2, stage 3, etc.). Instead, it groups cancers into localized, regional, and distant stages:

• Localized (sometimes referred to as stage 1): There is no sign the cancer has spread outside of the uterus.
• Regional: The cancer has spread outside the uterus to nearby structures or lymph nodes.
• Distant: The cancer has spread to distant parts of the body such as the lungs, liver, or bones.

Table 3. 5-year relative survival rates for endometrial cancer

SEER stage	5-year relative survival rate
Localized	94.9%
Regional	69.8%
Distant	18.4%
All SEER stages combined	52.2%

Footnotes:

• SEER = Surveillance, Epidemiology, and End Results. The SEER database is maintained by the National Cancer Institute (NCI), to provide survival statistics for different types of cancer.
• These numbers are based on people diagnosed with endometrial cancer between 2012–2018
• These numbers apply only to the stage of the cancer when it is first diagnosed. They do not apply later on if the cancer grows, spreads, or comes back after treatment.
• These numbers don’t take everything into account. Survival rates are grouped based on how far the cancer has spread, but your age, overall health, how well the cancer responds to treatment, and other factors can also affect your outlook.
• People now being diagnosed with endometrial cancer may have a better outlook than these numbers show. Treatments have improved over time, and these numbers are based on people who were diagnosed and treated at least five years earlier.

Keep in mind that survival rates are estimates and are often based on previous outcomes of large numbers of people who had a specific cancer, but they can’t predict what will happen in any particular person’s case. These statistics can be confusing and may lead you to have more questions. Your doctor knows your situation, so ask them how these numbers might apply to you.

[Source ³ ]

Generally for women with endometrial cancer in England between 2013 and 2017 ⁶⁵:

• 90 out of every 100 (90%) survive their cancer for 1 year or more after they are diagnosed
• around 75 out of every 100 (around 75%) will survive their cancer for 5 years or more
• more than 70 out of every 100 (more than 70%) will survive their cancer for 10 years or more after diagnosis

Endometrial cancer treatment

Treatment for endometrial cancer will be determined by your doctor(s) based on:

• Your overall health and medical history
• Extent of the disease (the stage)
• Your tolerance for specific medications, procedures or therapies
• Expectations for the course of the disease
• Your opinion or preference

The choice of treatment for endometrial cancer depends on the stage of cancer — whether it is only in the endometrium, or if it has spread to other parts of the uterus or body. Most people will be treated with surgery first to remove the uterus, fallopian tubes and ovaries. Some may need additional therapy. Another option is radiation therapy with energy beams, such as X-rays and protons, to kill cancer cells. Drug treatments for endometrial cancer include chemotherapy with powerful drugs and hormone therapy to block hormones that cancer cells rely on. Other options might be targeted therapy with drugs that attack specific weaknesses in the cancer cells and immunotherapy to help your immune system fight cancer.

Generally, treatment for people with cancer of the endometrium includes one or more of the following.

• Surgery. Treatment for endometrial cancer usually involves an operation to remove the uterus (hysterectomy), as well as to remove the fallopian tubes and ovaries (salpingo-oophorectomy). A hysterectomy makes it impossible for you to become pregnant in the future. Also, once your ovaries are removed, you’ll experience menopause, if you haven’t already. During surgery, your surgeon will also inspect the areas around your uterus to look for signs that cancer has spread. Your surgeon may also remove lymph nodes for testing. This helps determine your cancer’s stage.
• Radiation therapy. Radiation therapy uses powerful energy beams, such as X-rays and protons, to kill cancer cells. In some instances, your doctor may recommend radiation to reduce your risk of a cancer recurrence after surgery. In certain situations, radiation therapy may also be recommended before surgery, to shrink a tumor and make it easier to remove. If you aren’t healthy enough to undergo surgery, you may opt for radiation therapy only. Radiation therapy can involve:
  • Radiation from a machine outside your body. During external beam radiation, you lie on a table while a machine directs radiation to specific points on your body.
  • Radiation placed inside your body. Internal radiation (brachytherapy) involves placing a radiation-filled device, such as small seeds, wires or a cylinder, inside your vagina for a short period of time.
• Chemotherapy. Chemotherapy uses chemicals to kill cancer cells. You may receive one chemotherapy drug, or two or more drugs can be used in combination. You may receive chemotherapy drugs by pill (orally) or through your veins (intravenously). These drugs enter your bloodstream and then travel through your body, killing cancer cells. Chemotherapy is sometimes recommended after surgery if there’s an increased risk that the cancer might return. It can also be used before surgery to shrink the cancer so that it’s more likely to be removed completely during surgery. Chemotherapy may be recommended for treating advanced or recurrent endometrial cancer that has spread beyond the uterus.
• Hormone therapy. Hormone therapy involves taking medications to lower the hormone levels in the body. In response, cancer cells that rely on hormones to help them grow might die. Hormone therapy may be an option if you have advanced endometrial cancer that has spread beyond the uterus.
• Targeted drug therapy. Targeted drug treatments focus on specific weaknesses present within cancer cells. By blocking these weaknesses, targeted drug treatments can cause cancer cells to die. Targeted drug therapy is usually combined with chemotherapy for treating advanced endometrial cancer.
• Immunotherapy. Immunotherapy is a drug treatment that helps your immune system to fight cancer. Your body’s disease-fighting immune system might not attack cancer because the cancer cells produce proteins that blind the immune system cells. Immunotherapy works by interfering with that process. For endometrial cancer, immunotherapy might be considered if the cancer is advanced and other treatments haven’t helped.
• Supportive (palliative) care. Palliative care is specialized medical care that focuses on providing relief from pain and other symptoms of a serious illness. Palliative care specialists work with you, your family and your other doctors to provide an extra layer of support that complements your ongoing care. Palliative care can be used while undergoing other aggressive treatments, such as surgery, chemotherapy or radiation therapy. When palliative care is used along with all of the other appropriate treatments, people with cancer may feel better and live longer. Palliative care is provided by a team of doctors, nurses and other specially trained professionals. Palliative care teams aim to improve the quality of life for people with cancer and their families. This form of care is offered alongside curative or other treatments you may be receiving.

Surgery for endometrial cancer

Surgery to remove the uterus (hysterectomy) is recommended for most women with endometrial cancer. Most women with endometrial cancer undergo a procedure to remove the uterus (hysterectomy), as well as to remove the fallopian tubes and ovaries (salpingo-oophorectomy). A hysterectomy makes it impossible for you to have children in the future. Also, once your ovaries are removed, you’ll experience menopause, if you haven’t already. The surgeon who does the surgery is usually a specialist surgeon called a gynecological oncologist.

During surgery, your surgeon will also inspect the areas around your uterus to look for signs that cancer has spread. Your surgeon may also remove lymph nodes for testing. This helps determine your cancer’s stage.

In some cases, pelvic washings are done, the omentum is removed, and/or peritoneal biopsies are done. If the cancer has spread throughout the pelvis and abdomen (belly), a debulking procedure (removing as much cancer as possible) may be done.

Hysterectomy

The main treatment for endometrial cancer is surgery to take out the uterus and cervix. This operation is called a hysterectomy. When the uterus is removed through an incision (cut) in the abdomen (belly), it’s called a simple or total abdominal hysterectomy.

If the uterus is removed through the vagina, it’s known as a vaginal hysterectomy. This may be an option for women who are not healthy enough for other types of surgery.

When endometrial cancer has spread to the cervix or the area around the cervix (called the parametrium), a radical hysterectomy is done. In this operation, the entire uterus, the tissues next to the uterus (parametrium and uterosacral ligaments), and the upper part of the vagina (next to the cervix) are all removed. This operation is most often done through the abdomen, but it can also be done through the vagina.

The hospital stay for an abdominal hysterectomy is usually 3 to 7 days. The average hospital stay after an abdominal radical hysterectomy is about 5 to 7 days. Complete recovery can take up to 4 to 6 weeks. A laparoscopic procedure and vaginal hysterectomy usually require a hospital stay of 1 or 2 days and 2 to 3 weeks for recovery. Complications of these surgeries are not common and depend on the surgical approach. They include nerve or vessel damage, excessive bleeding, wound infection, blood clots, and damage to nearby tissues (the urinary and intestinal systems).

A radical hysterectomy affects the nerves that control the bladder, so a catheter is used to drain urine right after surgery. It’s often kept in for at least a few days. If the bladder hasn’t recovered completely when the catheter removed, it may be put back in. Another option is that you’re shown how to put a catheter yourself several times a day to empty your bladder. Over time, bladder function returns.

Surgeries done along with hysterectomy

It’s rare to remove the uterus but not the ovaries when treating endometrial cancer. (Still, it might be done in certain cases for women who are premenopausal.) Removing the ovaries and fallopian tubes is called a bilateral salpingo-oophorectomy (BSO). It isn’t really part of a hysterectomy. It’s a separate procedure that’s done during the same operation.

To decide what stage the cancer is in, lymph nodes in the pelvis and around the aorta also need to be removed. This is called lymph node dissection. It can be done through the same incision as the abdominal hysterectomy. If the hysterectomy is done vaginally, lymph nodes can be removed with laparoscopic surgery.

Bilateral salpingo-oophorectomy

Bilateral salpingo-oophorectomy operation removes both fallopian tubes and both ovaries. Bilateral salpingo-oophorectomy is usually done at the same time the uterus is removed (either by simple hysterectomy or radical hysterectomy) to treat endometrial cancers. Removing both ovaries means that you’ll go into menopause if you haven’t done so already.

If you’re younger than 45 and have stage 1 endometrial cancer, you may want to talk to your surgeon about keeping your ovaries. Even though women whose ovaries are removed might have a lower chance of the cancer coming back, removing the ovaries doesn’t seem to help them live longer.

Lymph node surgery

Pelvic and para-aortic lymph node dissection is an operation done to remove lymph nodes from the pelvis and the area next to the aorta. The lymph nodes are tested to see if they contain cancer cells that have spread from the endometrial tumor. This information is part of finding the surgical stage of the cancer.

The surgery is called a lymph node dissection when most or all of the lymph nodes in the area are removed. This is usually done at the same time as the operation to remove the uterus (hysterectomy). If you’re having an abdominal hysterectomy, the lymph nodes can be removed through the same incision. In women who have had a vaginal hysterectomy, lymph nodes may be removed by laparoscopic surgery.

When only a few of the lymph nodes in an area are removed, it’s called lymph node sampling.

Depending on the cancer type and grade, the amount of cancer in the uterus (tumor size), and how deeply the cancer invades the muscle of the uterus, and imaging test results , lymph nodes might not need to be removed.

Sentinel lymph node mapping

Sentinel lymph node mapping may be used in early-stage endometrial cancer if imaging tests don’t clearly show signs that cancer has spread to the lymph nodes in your pelvis. To do this, a blue or green dye is injected into the area with the cancer, near the cervix. The surgeon then looks for the lymph nodes that turn blue or green (from the dye). These lymph nodes are the ones that the cancer would first drain into (the sentinel nodes). They’re removed and tested to see if there are cancer cells in them. If so, more lymph nodes are taken out because they likely have cancer cells in them, too. If there are no cancer cells in sentinel nodes, no more nodes are removed. This procedure is usually done at the same time as surgery to remove the uterus (hysterectomy). Your doctor will talk with you about whether sentinel lymph node mapping is an option for you.

Pelvic washings (peritoneal lavage)

In this procedure, the surgeon “washes” the abdominal and pelvic cavities with salt water (saline). The fluid is then collected (using suction) and sent to the lab to see if it contains cancer cells. This is also called peritoneal lavage. If there are endometrial cancer cells in the fluid, the cancer stage may change (the surgical stage) and the next steps of treatment could be impacted.

Other procedures that might be used to look for cancer spread

• Omentectomy: The omentum is the layer of fatty tissue that covers the abdominal contents, sort of like an apron. Cancer sometimes spreads to this tissue. When this tissue is taken out, it’s called an omentectomy. This may be done during a hysterectomy if cancer has spread there. Biopsies of the omentum might also be done to check for cancer spread. Small pieces are taken out and tested for cancer cells.
• Peritoneal biopsies: The tissue lining the pelvis and abdomen is called the peritoneum. Peritoneal biopsies remove small pieces of this lining to check for cancer cells.

Tumor debulking

If cancer has spread throughout the abdomen, the surgeon might try to take out as much of the tumor as possible. This is called debulking. Debulking a cancer can help other treatments, like radiation or chemotherapy, work better. So, it might be helpful in treating some types of endometrial cancer.

Side effects of surgery

Any hysterectomy causes infertility (you won’t be able to get pregnant). For women who were premenopausal before surgery, removing the ovaries will cause menopause right away. This can lead to symptoms like hot flashes, night sweats, and vaginal dryness. Long-term, it can lead to osteoporosis and increased risk for heart disease, which impact all post-menopausal women. Surgery and menopausal symptoms can also affect your sex life.

Removing lymph nodes in the pelvis can lead to a build-up of fluid in the legs and genitals. This can become a life-long problem called lymphedema. It’s more likely if radiation is given after surgery.

Talk with your treatment team about side effects you might have right after surgery and later on. There might be things you can do to help prevent side effects. Know what to expect so you can get help right away.

Radiation therapy for endometrial cancer

Radiation therapy uses powerful energy beams, such as X-rays and protons, to kill cancer cells. In some instances, your doctor may recommend radiation to reduce your risk of a cancer recurrence after surgery. In certain situations, radiation therapy may also be recommended before surgery, to shrink a tumor and make it easier to remove.

If you aren’t healthy enough to undergo surgery, you may opt for radiation therapy only. In women with advanced endometrial cancer, radiation therapy may help control cancer-related pain.

Radiation therapy can be given in 2 ways to treat endometrial cancer:

• By putting radioactive materials inside the body, such as small seeds, wires or a cylinder, inside your vagina for a short period of time. This is called internal radiation therapy or brachytherapy.
• By using a machine that focuses beams of radiation at the tumor, much like having an x-ray. This is called external beam radiation therapy. During external beam radiation, you lie on a table while a machine directs radiation to specific points on your body.

In some cases, both brachytherapy and external beam radiation therapy are used. When that’s done, the external beam radiation is usually given first, followed by the brachytherapy. The stage and grade of the cancer are used to help decide what areas need to be treated with radiation therapy and which types of radiation are used.

Radiation is most often used after surgery to treat endometrial cancer. It can kill any cancer cells that may still be in the treated area. If your treatment plan includes radiation after surgery, you will be given time to heal before starting radiation. Often, at least 4 to 6 weeks are needed.

Less often, radiation might be given before surgery to help shrink a tumor so it’s easier to remove.

Women who are not healthy enough for surgery may get radiation as their main treatment.

Brachytherapy

Women who have had their uterus (and cervix) removed may have the upper part of the vagina treated with brachytherapy. This is called vaginal brachytherapy. A source of radiation (a radioactive material) is put into a cylinder (called an applicator) and the cylinder is put into the vagina. (It feels a lot like a snug tampon.) The size of the cylinder and how much radiation is in it depend on each case. The upper part of the vagina, closest to the uterus, is always treated. With brachytherapy, the radiation mainly affects the area of the vagina in contact with the cylinder. Nearby structures like the bladder and rectum get less radiation exposure.

This procedure is done in the radiation therapy area of a hospital or a radiation treatment center. There are 2 types of brachytherapy used for endometrial cancer, low-dose rate (LDR) and high-dose rate (HDR).

• In low-dose rate (LDR) brachytherapy, the applicator with the radiation source in it is left in for about 1 to 4 days. The patient needs to be still to keep the applicator from moving during treatment, so she’s usually needs to stay in the hospital during treatment. Because the patient has to stay immobile, this form of brachytherapy carries a risk of serious blood clots in the legs (called deep venous thrombosis or DVT). Low-dose rate (LDR) isn’t commonly used in the US.
• In high-dose rate (HDR) brachytherapy, the radiation is stronger. Each treatment takes a very short time (usually less than an hour), and the radiation is only in for 10 to 20 minutes. The applicator is only in place when the treatment is done. You will be able to go home the same day. For endometrial cancer, high-dose rate (HDR) brachytherapy might be given weekly or even daily for at least 3 doses.

The most common side effect is changes in the lining of the vagina called radiation vaginitis. If needed, pain medicines can be used to help you be more comfortable while the applicator is in.

External beam radiation therapy

In external beam radiation therapy the radiation is delivered from a source outside of the body.

External beam radiation therapy is often given 5 days a week for 4 to 6 weeks. The skin covering the treatment area is carefully marked with permanent ink or tiny tattoos. A special mold of the pelvis and lower back is custom made to make sure you are in the exact same position for each treatment. Each treatment takes less than a half-hour, but daily visits to the radiation center are needed.

Sometimes chemotherapy is given along with the radiation to help it work better. This is called chemoradiation.

Side effects of radiation therapy

Short-term side effects

Common side effects of radiation therapy include tiredness, upset stomach, or loose stools. Severe fatigue, which may not start until about 2 weeks after treatment begins, is also common. Diarrhea is common, but usually can be controlled with over-the-counter medicines. Nausea and vomiting may occur, but can be treated with medicine. These side effects are more common with external beam radiation than with brachytherapy.

Side effects tend to be worse when chemotherapy is given with radiation.

Skin changes, which can range from mild redness to peeling and blistering, are quite common. The skin may release fluid, which can lead to infection, so care must be taken to clean and protect the area exposed to radiation. Sometimes, as it heals, the skin in the treated area becomes darker or less flexible (harder).

Radiation can irritate the bladder, and you might have problems urinating. Irritation to the bladder, called radiation cystitis, can result in discomfort, blood in the urine, and an urge to urinate often.

Radiation can also cause irritation in the intestine. Rectal irritation or bleeding is called radiation proctitis. It’s sometimes treated with enemas that contain a steroid (like hydrocortisone) or suppositories that contain an anti-inflammatory.

Radiation can irritate the vagina, leading to discomfort and drainage (a discharge). This is called radiation vaginitis. If it occurs, the doctor may recommend douching with a dilute solution of hydrogen peroxide. When the irritation is severe, open sores can develop in the vagina, which may need to be treated with an estrogen cream.

Radiation can also lead to low blood counts, causing anemia (low red blood cells) and leukopenia (low white blood cells). The blood counts usually return to normal within a few weeks after radiation is stopped.

Long-term side effects

Radiation therapy may cause changes to the lining of the vagina leading to vaginal dryness. This is more common after vaginal brachytherapy than after pelvic radiation therapy. In some cases scar tissue can form in the vagina. The scar tissue can make the vagina shorter or more narrow (called vaginal stenosis), which can make sex (vaginal penetration) painful. A woman can help prevent this problem by stretching the walls of her vagina several times a week. This can be done by having sex 3 to 4 times a week or by using a vaginal dilator (a plastic or rubber tube used to stretch out the vagina). Still, vaginal dryness and pain with sex can be long-term side effects of radiation. Some centers have physical therapists who specialize in pelvic floor therapy which can help to treat these vaginal symptoms and sometimes improve sexual function. Ask your doctor about this if you are bothered by these problems.

Pelvic radiation can damage the ovaries, resulting in premature menopause. This is not an issue for most women treated for endometrial cancer because they have already gone through menopause, either naturally or as a result of surgery to treat the cancer (hysterectomy and removal of the ovaries).

Pelvic radiation therapy can also lead to blockages that keep fluid from draining out of the leg. This can lead to severe swelling, called lymphedema. Lymphedema is a long-term side effect; it doesn’t go away after radiation is stopped. In fact it may not start for several months or even years after treatment ends. This side effect is more common if pelvic lymph nodes were removed during surgery to remove the cancer. There are specialized physical therapists who can help treat this. It’s important to start treatment right away if you develop it.

Radiation to the pelvis can weaken the bones, leading to fractures of the hips or pelvic bones. It’s important that women who have had endometrial cancer contact their doctor right away if they have pelvic pain. Such pain might be caused by a fracture, recurrent cancer (cancer that’s come back after treatment), or other serious conditions.

Pelvic radiation can also lead to long-term problems with the bladder (radiation cystitis) or bowel (radiation proctitis). Rarely, radiation damage to the bowel can cause a blockage (called obstruction) or for an abnormal connection to form between the bowel and the vagina or outside skin (called a fistula). These conditions may need to be treated with surgery.

If you are having side effects from radiation, discuss them with your doctor. There are things you can do to get relief from these symptoms or to prevent them from happening.

Hormone therapy for endometrial cancer

Hormone therapy involves taking hormones or hormone-blocking drugs to treat cancer. Hormone therapy for endometrial cancer is not the same as the hormone therapy given to ease the symptoms of menopause (menopausal hormone therapy). Hormone therapy is most often used to treat endometrial cancer that’s advanced (stage 3 or 4) or has come back after treatment (recurred). Hormone therapy is often used along with chemotherapy.

Hormone treatment for endometrial cancer can include:

• Progestins. This is the main hormone treatment used.
• Tamoxifen
• Luteinizing hormone-releasing hormone agonists (LHRH agonists)
• Aromatase inhibitors

At this time, no one type of hormone treatment has been found to be the best for endometrial cancer.

Progestins

The main hormone treatment for endometrial cancer uses progesterone or drugs like it called progestins (man made progesterone). The 2 most commonly used progestins are:

• Medroxyprogesterone acetate (Provera®), which can be given as an injection or as a pill
• Megestrol acetate (Megace®), which is given as a pill or liquid

These drugs slow the growth of endometrial cancer cells. They’ve been found to be useful in treating women with endometrial cancer who want to be able to get pregnant in the future, and this is an area of research interest.

Side effects of progestins can include:

• Hot flashes
• Night sweats
• Weight gain (from fluid retention and an increased appetite)
• Worsening of depression
• Increased blood sugar levels in women with diabetes
• Serious blood clots (this is rare)

Sometimes endometrial hyperplasia and early endometrial cancers can be treated with an intrauterine device (IUD) that contains a progestin called levonorgestrel. This may be combined with another hormone drug, like medroxyprogesterone acetate or a luteinizing hormone-releasing hormone agonist (LHRH agonist).

Tamoxifen

Tamoxifen is an anti-estrogen drug often used to treat breast cancer. Tamoxifen might also be used to treat advanced or recurrent endometrial cancer. Alternating progesterone and tamoxifen is an option that seems to work well and be better tolerated than progesterone alone.

The goal of tamoxifen therapy is to keep any estrogens in the woman’s body from boosting the growth of the cancer cells. Though tamoxifen may keep estrogen from “feeding” the cancer cells, it acts like a weak estrogen in other parts of the body. It doesn’t cause bone loss, but it can cause hot flashes and vaginal dryness. Women taking tamoxifen also are at higher risk for serious blood clots in the legs.

Luteinizing hormone-releasing hormone agonists

Most women with endometrial cancer have had their ovaries removed as a part of treatment. Some women might have had radiation treatments that made their ovaries inactive. This helps keep the body from making estrogen and may also slow the growth of the cancer.

Luteinizing hormone-releasing hormone agonists (LHRH agonists) are drugs that lower estrogen levels in women who still have working ovaries. These drugs “turn off” the ovaries in women who are premenopausal so they don’t make estrogen.

Goserelin (Zoladex®) and leuprolide (Lupron®) are drugs that might be used to treat endometrial cancer. They’re given as a shot every 1 to 3 months. These drugs are also called gonadotropin-releasing hormone (GNRH) agonists.

Side effects of LHRH agonists can include any of the symptoms of menopause, such as hot flashes and vaginal dryness. They can also cause muscle and joint aches. If taken for a long time (years), these drugs can weaken bones, sometimes leading to osteoporosis.

Aromatase inhibitors

Even after the ovaries are removed (or are not working), estrogen is still made in fat tissue. This becomes the body’s main source of estrogen. Drugs called aromatase inhibitors can stop this estrogen from being made and lower estrogen levels even further. Examples of aromatase inhibitors include letrozole (Femara®), anastrozole (Arimidex®), and exemestane (Aromasin®). These drugs are most often used to treat breast cancer, but can be helpful in treating endometrial cancer, too. They’re most often used to treat women who cannot have surgery, but doctors are looking at other ways these drugs could be helpful.

Side effects of aromatase inhibitors can include headaches, joint and muscle pain, and hot flashes. If taken for a long time (years), these drugs can weaken bones, sometimes leading to osteoporosis. These drugs are still being studied for how to best use them to treat endometrial cancer.

Chemotherapy for endometrial cancer

Chemotherapy also called chemo, uses chemicals to kill cancer cells. You may receive one chemotherapy drug, or two or more drugs can be used in combination. In most cases, a combination of chemo drugs is used. Combination chemotherapy tends to work better than one drug alone. You may receive chemotherapy drugs by pill (orally) or through your veins (intravenously). Chemotherapy may be recommended for women with advanced or recurrent endometrial cancer that has spread beyond the uterus. These drugs enter your bloodstream and then travel through your body, killing cancer cells.

Chemo is also commonly used for high grade cancers, which grow and spread quickly, and cancer that comes back after treatment.

Chemotherapy is not used to treat stage 1 and 2 endometrial cancers.

Chemotherapy is often given in cycles: a period of treatment, followed by a rest period. The chemo drugs may be given on one or more days in each cycle.

Chemotherapy drugs used to treat endometrial cancer may include:

• Paclitaxel (Taxol®)
• Carboplatin
• Doxorubicin (Adriamycin®) or liposomal doxorubicin (Doxil®)
• Cisplatin
• Docetaxel (Taxotere®)

Most often, 2 or more drugs are combined for treatment. The most common combinations include carboplatin/paclitaxel and cisplatin/doxorubicin. Less often, carboplatin/docetaxel and cisplatin/paclitaxel/doxorubicin may be used.

For carcinosarcoma, the chemo drug ifosfamide (Ifex®) is often used, either alone or along with either cisplatin or paclitaxel. The targeted drug called trastuzumab (Herceptin®) might be added for carcinosarcomas that are HER2 positive. (HER2 is a protein that helps some cancer cells grow and spread faster.

Sometimes chemo is given for a few cycles, followed by radiation. Then chemo is given again. This is called sandwich therapy. It’s sometimes used for endometrial papillary serous cancer and uterine carcinosarcoma.

Another treatment option is to give chemo with radiation (called chemoradiation). The chemo can help the radiation work better, but it can be harder on the patient because the combination causes more side effects.

Side effects of chemotherapy

These drugs kill cancer cells but can also damage some normal cells, which in turn causes side effects. Side effects of chemotherapy depend on the drugs used, the amount taken, and how long treatment is given. Common side effects include:

• Nausea and vomiting
• Loss of appetite
• Mouth sores
• Vaginal sores
• Hair loss

Also, most chemo drugs can damage the blood-producing cells of the bone marrow. This can result in low blood cell counts, such as:

• Low white blood cells, which increases the risk of infection
• Low platelet counts, which can cause bleeding or bruising after minor cuts or injuries
• Low red blood cells (anemia), which can cause problems like fatigue and shortness of breath

Most of the side effects of chemotherapy get better over time when treatment ends, but some can last a long time. Different drugs can cause different side effects. For instance, doxorubicin can damage the heart muscle over time. The chance of heart damage goes up as the total dose of the drug goes up, so doctors put a limit on how much doxorubicin a person can get.

Cisplatin can cause kidney damage, so you’ll be given lots of intravenous fluids before and after chemo to help protect the kidneys. Both cisplatin and paclitaxel can cause nerve damage (called neuropathy). This can lead to numbness, tingling, or even pain in the hands and feet. Ifosfamide can injure the lining of the bladder, causing it to bleed (called hemorrhagic cystitis). To prevent this, you might be given large amounts of intravenous fluids and a drug called mesna along with the chemo.

Before starting chemotherapy, be sure to discuss the drugs and their possible side effects with your health care team.

If you have side effects while on chemotherapy, remember that there are ways to prevent or treat most of them. For instance, there are many anti-nausea drugs that can help prevent or reduce nausea and vomiting. Be sure to tell your health care team about any side effects you have. Treating them right away can often keep them from getting worse.

Targeted therapy for endometrial cancer

Targeted therapy is treatment with drugs that are made to target certain changes in the cancer cells. Targeted therapy drugs work differently from standard chemotherapy (chemo) drugs. They tend to have different (and sometimes less severe) side effects than chemo.

Targeted therapy is used to treat many types of cancer, but it’s still fairly new in the treatment of endometrial cancer. Only a few of these drugs are in use at this time. Some of these are only given as part of a clinical trial, but many more are being studied. These drugs are mostly used to treat high-risk endometrial cancers and those that have spread (metastasized) or come back (recurred) after treatment.

Lenvatinib

Lenvatinib (Lenvima) is a type of drug known as a kinase inhibitor. It helps block tumors from forming new blood vessels, as well as targeting some of the proteins in cancer cells that normally help them grow. It can be used along with the immunotherapy drug pembrolizumab (Keytruda) to treat some advanced endometrial cancers, typically after at least one other drug treatment has been tried.

Lenvatinib is taken as capsules once a day.

Common side effects of lenvatinib (Lenvima) include diarrhea, fatigue, joint or muscle pain, loss of appetite, nausea and vomiting, mouth sores, weight loss, high blood pressure, and swelling in the arms or legs. Less common but more serious side effects can include serious bleeding, blood clots, very high blood pressure, severe diarrhea, holes forming in the intestines, and kidney, liver, or heart failure.

Bevacizumab

Bevacizumab (Avastin) belongs to a class of drugs called angiogenesis inhibitors. For cancers to grow and spread, they need to make new blood vessels to nourish themselves (a process called angiogenesis). This drug attaches to a protein called vascular endothelial growth factor (VEGF), which signals new blood vessels to form and slows or stops cancer growth.

Bevacizumab is often given along with chemotherapy, but it can also be given alone, typically after other drug treatments have been tried.

Bevacizumab (Avastin) is given as an infusion into the vein (IV) every 2 to 3 weeks.

Common side effects of bevacizumab (Avastin) include high blood pressure, tiredness, bleeding, low white blood cell counts, headaches, mouth sores, loss of appetite, and diarrhea. Rare, but possibly serious side effects include blood clots, severe bleeding, slow wound healing, holes forming in the colon (perforations), and the formation of abnormal connections between the bowel and the skin or bladder (fistulas). If a perforation or fistula forms, it can lead to severe infection and surgery may be needed.

mTOR inhibitors

These drugs block a cell protein known as mTOR, which normally helps cells grow and divide into new cells. These drugs might be given alone or added to chemo or hormone therapy to treat advanced (higher stage) endometrial cancers, or those that come back after treatment.

• Everolimus (Afinitor) is taken as a pill once a day. Common side effects of everolimus (Afinitor) include mouth sores, diarrhea, nausea, feeling weak or tired, shortness of breath, and cough. Everolimus can also cause low blood counts, increase blood lipids (cholesterol and triglycerides), and raise your blood sugar, so your doctor will check your blood work often while you are taking this drug.
• Temsirolimus (Torisel) is given as an intravenous (IV) infusion, typically once a week. Temsirolimus (Torisel) can be given alone. The most common side effects of temsirolimus (Torisel) are skin rash, weakness, mouth sores, diarrhea, nausea, loss of appetite, fluid build-up in the face or legs, and increases in blood sugar and cholesterol levels. Rarely, more serious side effects have been reported.

Immunotherapy for endometrial cancer

Immunotherapy is treatment with drugs that help a person’s own immune system better recognize and kill cancer cells.

An important part of the immune system is its ability to keep itself from attacking the body’s normal cells. To do this, it uses “checkpoint” proteins on immune cells, which act like switches that need to be turned on (or off) to start an immune response. Cancer cells sometimes use these checkpoints to avoid being attacked by the immune system.

Drugs that target these checkpoints called immune checkpoint inhibitors can be used to treat some endometrial cancers.

PD-1 inhibitors

Pembrolizumab (Keytruda) and dostarlimab (Jemperli) are drugs that target PD-1, a protein on immune system cells called T cells. PD-1 normally helps keep T cells from attacking other cells in the body (including some cancer cells). By blocking PD-1, these drugs boost the immune response against cancer cells. This can shrink some tumors or slow their growth.

Pembrolizumab can be used by itself to treat advanced endometrial cancers, typically after other treatments have been tried, if surgery or radiation are not options, and if the cancer cells have any of the following:

• A high level of microsatellite instability (MSI-H) or a defect in a mismatch repair gene (dMMR)
• A high tumor mutational burden (TMB-H), meaning the cells have many gene mutations

Tumor cells can be tested for these changes.

Pembrolizumab (Keytruda) can also be used along with the targeted drug lenvatinib (Lenvima) to treat advanced endometrial cancers that are not MMR deficient (dMMR) or MSI high (MSI-H), typically after at least one other drug treatment has been tried. This drug is given as an intravenous (IV) infusion, typically once every 3 or 6 weeks.

Dostarlimab (Jemperli) can be used to treat advanced or recurrent endometrial cancer, after chemotherapy has been tried, and if the cancer cells have a defect in a mismatch repair gene (dMMR). This drug is given as an intravenous (IV) infusion, typically once every 3 weeks at first, and then every 6 weeks.

Possible side effects of immune checkpoint inhibitors

Side effects of these drugs can include:

• Feeling tired or weak
• Fever
• Cough
• Nausea
• Itching
• Skin rash
• Loss of appetite
• Muscle or joint pain
• Shortness of breath
• Constipation or diarrhea

Other, more serious side effects occur less often. These can include:

• Infusion reactions: Some people might have an infusion reaction while getting one of these drugs. This is like an allergic reaction, and can include fever, chills, flushing of the face, rash, itchy skin, feeling dizzy, wheezing, and trouble breathing. It’s important to tell your doctor or nurse right away if you have any of these symptoms while getting one of these drugs.
• Autoimmune reactions: These drugs work by basically removing one of the safeguards on the body’s immune system. Sometimes this causes the immune system to attack other parts of the body, which can cause serious or even life-threatening problems in the lungs, intestines, liver, hormone-making glands, kidneys, skin, or other organs.

It’s very important to report any new side effects to your health care team right away. If you do have a serious side effects, treatment may need to be stopped and you may be given high doses of corticosteroids to suppress your immune system.

Treatment of endometrial cancer by stage

The stage of your endometrial cancer helps your doctor to decide which treatment you need. Treatment also depends on:

• the type of endometrial cancer you have
• how the endometrial cancer is likely to behave (the grade)
• your general health
• your preferences

Surgery is the first treatment for almost all women with endometrial cancer. The operation includes removing the uterus, fallopian tubes, and ovaries. This is called a total hysterectomy bilateral salpingo-oophorectomy (TH/BSO). Lymph nodes from the pelvis and around the aorta may also be removed (a pelvic and para-aortic lymph node dissection or sampling) and tested for cancer spread. Pelvic washings may be done, too. The tissues removed at surgery are tested to see how far the cancer has spread (the stage). Depending on the stage of the cancer, other treatments, such as radiation and/or chemotherapy may be recommended.

For some women who still want to be able to get pregnant, surgery may be put off for a time and other treatments tried instead.

If a woman isn’t well enough to have surgery, other treatments, like radiation, will be used.

Stage 1 endometrial cancer treatment

Stage 1 endometrial cancer is only in the uterus. It has not spread to lymph nodes or distant sites.

Stage 1 endometrioid cancers

Surgery is the main treatment for stage 1 endometrial cancer. Your surgeon removes your uterus and cervix. This is a hysterectomy. They usually also remove both of your fallopian tubes and ovaries. They may also remove lymph nodes in your pelvis to check for cancer cells. Sometimes this is the only treatment needed. The patient is then closely watched for signs that the cancer has come back (recurred).

For women with higher grade tumors, radiation will likely be recommended after surgery. Vaginal brachytherapy, pelvic radiation, or both can be used.

Women who have early endometrial cancer, have not been through the menopause and would like to have children may be able to have treatment that preserves their fertility (have surgery to remove their uterus without removing the ovaries). This prevents menopause and the issues that can come with it. This also increases the chance that the cancer will come back, but it doesn’t make it more likely that you will die from the cancer. It is not standard treatment. So talk to your specialist about your options and the possible risks. You will need to have treatment in a specialist center. This might not be your nearest hospital.

Women who cannot have surgery because of other medical problems or who are frail due to age are often treated with just radiation (external radiation and/or vaginal brachytherapy).

Fertility-sparing treatment for stage 1A grade 1 endometrioid cancers

For young women who still want to have children, surgery may be postponed while progestin therapy is used to treat the cancer. Progestin treatment can cause the cancer to shrink or even go away for some time, giving the woman a chance to get pregnant. Still, this is experimental and can be risky if the patient isn’t watched closely. An endometrial biopsy or a D&C should be done every 3 to 6 months. If there’s still no cancer after 6 months, the woman can try to become pregnant. She will continue to be checked for cancer every 6 months. Because the cancer often comes back again, doctors recommend total hysterectomy bilateral salpingo-oophorectomy (TH/BSO) after childbearing is complete.

Many times, progestin treatment doesn’t work and the cancer doesn’t get better or keeps growing. Putting off surgery can give the cancer time to spread outside the uterus. If it doesn’t go away in 6 to 12 months , surgery to remove and stage the cancer is recommended (hysterectomy and removal of both fallopian tubes and ovaries).

A second opinion from a gynecologic oncologist and pathologist (to confirm the grade of the cancer) before starting progestin therapy is important. Seeing a fertility expert is also a good idea. It’s important to understand that this isn’t a standard treatment and may increase risk of cancer growth and spread.

Other types of stage 1 endometrial cancers

Cancers such as papillary serous carcinoma, clear cell carcinoma, or carcinosarcoma are more likely to have already spread outside the uterus when diagnosed. Women with these types of tumors don’t do as well as those with lower grade tumors. If the biopsy done before surgery shows a high-grade cancer, the surgery may be more extensive. Along with the total hysterectomy and removal of both fallopian tubes and ovaries, the pelvic and para-aortic lymph node will be removed, and the omentum is often removed, too.

After surgery, chemotherapy (chemo) with or without radiation therapy are given to help keep the cancer from coming back. The chemo usually includes the drugs carboplatin and paclitaxel, but other drugs can also be used.

If the cancer can’t be removed with surgery, both chemotherapy (chemo) with or without and radiation are used. Sometimes, the tumor then shrinks so that surgery can then be done to remove it.

Stage 2 endometrial cancer treatment

When an endometrial cancer is stage 2, it has spread to the connective tissue of the cervix. But it still hasn’t grown outside the uterus.

One treatment option is to have surgery first, followed by radiation therapy. The surgery includes a radical hysterectomy (the entire uterus, the tissues next to the uterus, and the upper part of the vagina are removed), removal of both fallopian tubes and ovaries (BSO), and pelvic and para-aortic lymph node dissection or sampling. Radiation therapy, often both vaginal brachytherapy and external pelvic radiation, may be given after the patient has recovered from surgery. Another option is to give the radiation therapy first, and then do a simple hysterectomy, bilateral salpingo-oophorectomy (BSO) and possible lymph node dissection or lymph node sampling.

The lymph nodes that have been removed are checked for cancer cells. If there’s cancer in them, the cancer isn’t really a stage 2 – it’s a stage 3C endometrial cancer.

In some cases, a woman with early stage endometrial cancer might be too frail or ill from other diseases to safely have surgery. These women are treated with external radiation and brachytherapy.

For women with high-grade cancers, like papillary serous carcinoma or clear cell carcinoma, the surgery may include omentectomy and peritoneal biopsies along with the total hysterectomy, removal of both fallopian tubes and ovaries, pelvic and para-aortic lymph node dissections, and pelvic washings. After surgery, radiation therapy, chemo, or both may be given to help keep the cancer from coming back. The chemo usually includes the drugs carboplatin and paclitaxel or possibly cisplatin and doxorubicin.

Someone with a stage 2 uterine carcinosarcoma often has the same type of surgery that’s used for a high-grade cancer. After surgery, radiation, chemo, or both may be used. The chemo often includes paclitaxel and carboplatin but may instead include ifosfamide, along with paclitaxel or cisplatin.

Stage 3 endometrial cancer treatment

Stage 3 endometrial cancers have spread outside of the uterus.

If the surgeon thinks that all visible cancer can be removed, a hysterectomy is done and both ovaries and fallopian tubes are removed. Sometimes women with stage 3 cancers need a radical hysterectomy. A pelvic and para-aortic lymph node dissection may also be done. Pelvic washings will be done and the omentum may be removed. Some doctors will try to remove any remaining cancer (called debulking), but it isn’t clear that this helps patients live longer.

If tests done before surgery show that the cancer has spread too far to be removed completely, in rare cases, radiation therapy may be given before any surgery. It might shrink the tumor enough to make surgery an option. For advanced endometrial cancers that cannot be treated with surgery or radiation, treatment with the immunotherapy drug, pembrolizumab might be an option.

• Stage 3A endometrial cancer: A stage 3A endometrial cancer has spread to the tissue covering the uterus (the serosa) or to other tissues in the pelvis, like the fallopian tubes or the ovaries (the adnexa). For these cancers, treatment after surgery may include chemo, radiation, or both. Radiation is given to the pelvis or to both the abdomen (belly) and pelvis. Vaginal brachytherapy is often used, too.
• Stage 3B endometrial cancer: In stage 3B endometrial cancer, the cancer has spread to the vagina. After surgery, stage 3B may be treated with chemo and/or radiation.
• Stage 3C endometrial cancer: Stage 3C endometrial cancer includes cancers that have spread to the lymph nodes in the pelvis (stage 3C1) and those that have spread to the lymph nodes around the aorta (stage 3C2). Treatment includes surgery, followed by chemo and/or radiation.

For women with high-grade cancers, such as papillary serous carcinoma or clear cell carcinoma, the surgery may include omentectomy and peritoneal biopsies along with the total hysterectomy, removal of both ovaries and fallopian tubes, pelvic and para-aortic lymph node dissections, and pelvic washings. After surgery, chemo, radiation therapy, or both may be given to help keep the cancer from coming back. The chemo usually includes the drugs carboplatin and paclitaxel or cisplatin and doxorubicin.

Women with stage 3 uterine carcinosarcoma often have the same type of surgery that’s used for a high-grade cancer. After surgery, radiation, chemo, or both may be used. The chemo often includes the drug paclitaxel and carboplatin, but ifosfamide, along with paclitaxel or cisplatin may be used. Targeted and/or immunotherapy may also be options for some women.

Stage 4 metastatic endometrial cancer treatment

• Stage 4A endometrial cancer: Stage 4A endometrial cancers have grown into the bladder or bowel.
• Stage 4B endometrial cancer: Stage 4B endometrial cancers have spread to lymph nodes outside the pelvis or para-aortic area. This stage also includes cancers that have spread to the liver, lungs, omentum, or other organs.

Some endometrial cancers are stage 4 because they have spread to lymph nodes in the abdomen (and not just the pelvis and para-aortic area), but they haven’t spread to any other areas. Women with this kind of cancer spread may have better outcomes if all the cancer that’s seen can be removed (debulked) and biopsies of other areas in the abdomen do not show cancer cells.

In most cases of stage 4 endometrial cancer, the cancer has spread too far for it all to be removed with surgery. A hysterectomy and removal of both fallopian tubes and ovaries may still be done to prevent excessive bleeding. Radiation therapy may also be used for this reason. When the cancer has spread to other parts of the body, hormone therapy may be used. But high-grade cancers and those without detectable progesterone and estrogen receptors on the cancer cells are not likely to respond to hormone therapy.

Combinations of chemo drugs may help some women for a time. The drugs used most often are paclitaxel, doxorubicin, and either carboplatin or cisplatin. These drugs are often used together in combination. Stage 4 carcinosarcoma is often treated with much the same chemo. Cisplatin, ifosfamide, and paclitaxel may also be combined.

Targeted drugs and/or immunotherapy drugs may also be options for some women with advanced endometrial cancer.

Women with stage 4 endometrial cancer should consider taking part in clinical trials of chemotherapy or other new treatments.

Recurrent endometrial cancer treatment

Cancer is called recurrent when it come backs after treatment. Recurrence can be local (in or near the same place it started) or distant (spread to organs such as the lungs or bone). Treatment depends on the amount of cancer and where it is, as well as the kind of treatment was used the first time.

For local recurrences, such as in the pelvis, surgery (sometimes followed with radiation therapy) is used. For women who have other medical conditions that make them unable to have surgery, radiation therapy alone or combined with hormone therapy tends to be used.

For a distant recurrence, surgery and/or focused radiation therapy may be used when the cancer is only in a few small spots (like in the lungs or bones). Women with more extensive recurrences (widespread cancer) are treated like those with stage IV endometrial cancer. Either hormone therapy or chemo is recommended. Low-grade cancers containing progesterone receptors are more likely to respond well to hormone therapy. Higher-grade cancers and those without detectable receptors are unlikely to shrink during hormone therapy but may respond to chemo. Targeted therapy and immunotherapy may be used in some cases. Clinical trials of new treatments are another good option.

Supportive (palliative) care

Palliative care is specialized medical care that focuses on providing relief from pain and other symptoms of a serious illness. Palliative care specialists work with you, your family and your other doctors to provide an extra layer of support that complements your ongoing care. Palliative care can be used while undergoing other aggressive treatments, such as surgery, chemotherapy or radiation therapy.

When palliative care is used along with all of the other appropriate treatments, people with cancer may feel better and live longer.

Palliative care is provided by a team of doctors, nurses and other specially trained professionals. Palliative care teams aim to improve the quality of life for people with cancer and their families. This form of care is offered alongside curative or other treatments you may be receiving.

Coping and support

Coping with the shock, fear and sadness that come with a cancer diagnosis can take time. You may feel overwhelmed just when you need to make crucial decisions. With time, each person finds a way of coping and coming to terms with the diagnosis.

Until you find what brings you the most comfort, consider trying to:

• Find out enough about endometrial cancer to make decisions about your care. Ask your doctor for the specifics about your cancer, such as its type and stage. And ask for recommended sources of information where you can learn more about your treatment options. The National Cancer Institute ⁶⁶ and the American Cancer Society ⁶⁷ are good places to start.
• Stay connected to friends and family. Your friends and family can provide a crucial support network for you during your cancer treatment. As you begin telling people about your endometrial cancer diagnosis, you’ll likely get offers for help. Think ahead about things you may like help with, whether it’s having someone to talk to if you’re feeling low or getting help preparing meals.
• Find someone to talk to. You might have a close friend or family member who’s a good listener. Or talk to a counselor, medical social worker, or pastoral or religious counselor.

Consider joining a support group for people with cancer. You may find strength and encouragement in being with people who are facing the same challenges you are. Ask your doctor, nurse or social worker about groups in your area. Or try online message boards, such as those available through the American Cancer Society ⁶⁷.

References

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