Endometrial: The Most Common Reproductive Cancer in Women

There are several components of surgery to determine the stage of the cancer and its early treatment: "pelvic washing" to collect and analyze the cancerous cells, exploration of abdominal cavity with biopsies as needed, hysterectomy, removal of the ovaries, and dissection of the lymph nodes of the pelvis. Removal of the lymph nodes (lymphadenectomy) in patients with early stage cancer is still controversial. Some doctors may opt to skip the lymphadenectomy if the patient is at low risk for the cancer spreading through the lymph system.

Minimally invasive procedures, like laparoscopy, are becoming increasingly common for the initial surgical staging and treatment of endometrial cancer. Complications during the surgery tend to be about the same for laparoscopy and regular surgery (laparotomy). But laparoscopy patients may have fewer adverse events after surgery and had a lower risk for having a prolonged hospital stay, compared to women who have conventional surgery, which suggests that laparoscopy may be an effective alternative.

Radiation Therapy

Radiation therapy may be used in addition to surgery. There has been a lot of debate about whether it really helps the outcome, however. Some studies have found that it can help control the cancer in an immediate way, but the likelihood of metastasis -- recurrence of the cancer at the site at which it started -- and one's five-year survival odds may not be significantly affected by radiation. Some studies found that despite a decrease in local recurrence, there was also an increase in gastrointestinal toxicities.

Other methods like vaginal brachytherapy, in which radioactive material is placed directly in the body, were linked to significantly reduced rates of gastrointestinal toxicity, so doctors may opt for this treatment over conventional (external beam) radiation. Each case of endometrial cancer is different, and doctors will look at all the variables and weigh all the options before determining an appropriate course of treatment.

Chemotherapy

Chemotherapy is another common treatment for endometrial cancer, especially in later stages of the disease (stages III and IV). Many studies have looked at the effectiveness and the adverse effects of chemotherapy in endometrial cancer treatment, and the debate is ongoing. The three most effective chemotherapeutic compounds are platinum (cisplatin and carboplatin), taxanes (paclitaxel), and doxorubicin. They are commonly used alone or in combination for the treatment of advanced cases of cancer. The response rates (how likely the cancer is to be affected by the chemicals) ranges from 20 percent to over 40 percent. Other cytotoxic agents including 5-fluorouracil, vincristine, ifosfamide, and ixabepilone are less supported by the research, but may be somewhat effective as well.

Studies comparing the different forms of chemotherapy against one another have found that there are pros and cons to each. In one study, women who got by cisplatin and doxorubin (AP) or cisplatin plus doxorubicin plus paclitaxel (TAP) had about the same rates of survival and of recurrence. But in further analysis, TAP was linked to a 50 percent reduction in the risk of recurrence, but it also carried a greater risk of serious side effects. Other studies are currently underway to determine the effectiveness and adverse events associated with other combinations of chemotherapy drugs.

Hormone Therapy

Hormonal therapy using high doses of progestins (progesterone) is another treatment option for patients with advanced or recurrent endometrial cancers. Before hormonal therapy can be used, however, the tumor has to be tested for expression of estrogen and progesterone receptors. The response rates approach 20 percent in the presence of estrogen and progesterone receptors, but some research has found that this form of therapy is not useful in preventing relapse or prolonging lifespan, although there were some shortcomings in the design of the study. Combining daily tamoxifen with weekly progesterone may be more effective treatment option for advanced or recurrent endometrial cancer.

Biologics Could Be Promising in the Future

Over the past several years, there has been increasing interest in biological therapy for treating cancer, especially in advanced and recurrent endometrial cancer. Biologics don't attack the cancer cells directly, as with chemotherapy -- rather, they help the immune system fight the cancer more effectively. Some trials have shown promise for a drug called bevacizumab, administered to patients with recurrent or persistent endometrial cancer. But these methods are still new, and more research needs to be done to determine how safe they are, and how effective.

Recurrent Endometrial Cancers

For women who have recurring endometrial cancer, the treatment options are somewhat limited. Vaginal recurrences can often be treated with radiation therapy. For women who initially undergo surgery, radiation can be an effective option if the cancer reoccurs in the vagina.

For cancers that occur at a single site, surgery and/or radiation may be successful. For cancers that occur at distant sites from the original location, chemotherapy, biologic or hormonal agents, as previously discussed, can be used.

SYNDROMES THAT RAISE ONE'S RISK FOR ENDOMETRIAL CANCER

A small percentage (three to five percent) of women who have endometrial cancer may have what is known as "site-specific cancer susceptibility syndromes." These syndromes elevate one's risk for developing several forms of cancer, including endometrial, and involve specific gene mutations. They also increase one's risk for developing cancers at an earlier age than the average.

Lynch Syndrome

Lynch syndrome is a genetic condition that increases one's risk for a specific type of colorectal cancer known as hereditary nonpolyposis colorectal cancer (HNPCC), and accounts for the majority of inherited cases of endometrial cancer. It can affect both women and men. The average age of diagnosis of endometrial cancer in patients with Lynch syndrome is 46 years old. Individuals affected by this syndrome are at risk for a number of cancers, including colon, endometrial, ovarian, gastric, intestinal, hepatobilliary tract, upper urinary tract, brain, and skin cancers.

Researchers have outlined the gene mutations involved in Lynch syndrome, which occur in the repair system of the DNA. The inheritance pattern for the disorder is autosomal dominant, meaning that only one parent needs to have the mutation in order for a child to inherit it.

The estimated risk of developing colon cancer in women affected with Lynch syndrome is 40 to 60 percent. Additionally, for women with Lynch syndrome, their lifetime endometrial cancer risk equals or exceeds their risk of developing colon cancer. Based on the specific types of genetic mutations a woman has, her risk for developing endometrial cancer is between 40 and 70 percent.

Cowden Syndrome

Cowden syndrome was first described in 1963 and is named after a patient. It is a rare inherited disorder that can affect both sexes, and the criteria doctors use for diagnosis continue to evolve. Individuals afflicted with Cowden syndrome (CS) have an increased risk of developing several types of cancer: breast, thyroid, and uterus. Women who have CS have a higher risk -- 19 percent -- of developing endometrial cancer by age 70.

Signs and symptoms of CS include lesions on the mucous membranes of the nose and mouth, growths in the gastrointestinal system (called hamartomatous gastrointenstinal polyps), enlarged head (macrocephaly), thyroid disease, benign breast disease, breast cancer, and endometrial cancer. The overwhelming majority of patients will show clinical signs (lesions of the mucous membranes) by age 29.

Approximately one in 200,000 people have CS. Like Lynch syndrome, in CS only one parent has to have the mutation to pass it on to the child, making it an autosomal dominant mutation. Researchers have uncovered the specific mutations involved in CD: a particular mutation in PTEN, a tumor suppressor is found in approximately 80 percent of patients with CS. Mutations in the gene are found in an array of sporadic tumors, such as thyroid, endometrium, prostate, breast, brain, and endometrial cancer.

Diagnosis and Management for Lynch and Cowden Syndromes

A detailed family history helps doctors identify patients and their families who may have a genetic cancer predisposition, like Lynch or Cowden syndromes. Genetic testing can be done for women thought to be at risk for having Lynch syndrome. Sometimes hysterectomy along with removal of the ovaries may be recommended for women with Lynch syndrome in order to prevent endometrial and ovarian cancers from occurring.

Diagnostic criteria for Cowden syndrome have evolved over the years. The most recent is the Cleveland Clinic scoring system in 2011. For an individual patient, the probability of a relevant gene mutation may be evaluated by the Cleveland Clinic web calculator.

OUTCOMES FOR PATIENTS AND FUTURE DIRECTIONS

Endometrial cancer patients tend to experience vaginal bleeding and pelvic discomfort early in the disease process which, fortunately, leads to early diagnosis. As a result, 75 percent of the patients are diagnosed with early-stage carcinomas and will survive their disease. The survival rate by the stage of the cancer approaches 85 percent for stage I, 75 percent for stage II, 45 percent for stage III and 25 percent for stage IV. However, these rates can vary considerably, as they depend on many variables, like the type of cancer cells that are present.

Several factors are associated with prognosis for women with endometrial cancer. These include histologic type, the woman's age at diagnosis, tumor grade and stage, how deep into the uterus the cancer cells have grown, and whether or not the cancer has invaded the lymph or vascular systems.

Much is known about endometrial cancer, but there is also much about it that is still a mystery. The risk models are imperfect, and can make treatment difficult. For example, some women who are thought to be at low risk may experience recurrences, while others probably receive unnecessary, costly and potentially toxic treatments. In the future, a better understanding of the biomarkers associated with endometrial cancer is expected to help doctors determine a woman's risk more accurately, and develop the best method of treatment. Learning more about the genetics of endometrial cancer should also lead to earlier detection, and an even better prognosis for patients who are affected by it.

Image: vetpathologist/Shutterstock.


This article originally appeared on TheDoctorWillSeeYouNow.com, an Atlantic partner site.

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Presented by

Yevgeniya Ioffe & Israel Zighelboim

Yevgeniya Ioffe and Israel Zighelboim both work in the Division of Gynecologic Oncology at the Washington University School of Medicine and Siteman Cancer Center in St. Louis.

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